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Using Technology to Study

Cellular and Molecular Biology

under a contract from the

National Institutes of Health

National Center for Research Resources

5415 Mark Dabling Boulevard

Colorado Springs, Colorado 80918

BSCS Development Team

Design Conference Participants

Rodger Bybee, Principal Investigator

Philip Bourne, University of California San Diego, La Jolla,

Jerry Phillips, Project Director

California

April Gardner, Curriculum Developer

David Gorenstein, University of Texas Galveston, Galveston, Texas

Sharmila Basu, Curriculum Developer

Amy Lee, King Kekaulike High School, Pukalani, Hawaii

Carrie Hamm, Project Assistant

Maryann Martone, University of California San Diego, San Diego,

Ted Lamb, Evaluator

California

Barbara Perrin, Production Director

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BSCS Administrative Staff

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New York

Rodger W. Bybee, Executive Director

Michael Schmid, Baylor College of Medicine, Houston, Texas

Pam Van Scotter, Director, Curriculum Development Center

Rich Wasserman, Sand Creek High School, Colorado Springs,

Janet Carlson Powell, Associate Director, Chief Science

Colorado

Education Officer

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Larry Satkowiak, Associate Director, Chief Operating Officer

Primary Field-Test Teachers

National Institutes of Health

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Krishan Arora, Health Scientist Administrator, National Center

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for Research Resources

Patricia Carothers, Monte Vista High School, Danville, California

Bruce Fuchs, Director, Office of Science Education

Carlos Charriez, Northwest High School, Germantown, Maryland

William Mowczko, Project Officer, Office of Science Education

Brenda Chenier, Eastern Senior High School, Washington, District

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Secondary Field-Test Teachers

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Cover Illustration

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The structure of the oncogene H-Ras p21 protein complexed with

Jeff Ludden, Multimedia Programmer

GTP on the cover photograph was taken from the Protein Data

Pat Leffas, Multimedia Programmer

Bank (PDB) ( http://www.pdb.org), protein number PDB ID: 121P.

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ings, conclusions, or recommendations expressed in this publica-

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Copyright © 2005 by BSCS. All rights reserved. You have the per-

Leemor Joshua-Tor, Cold Spring Harbor Laboratory, Cold Spring

mission of BSCS to reproduce items in this module for your class-

Harbor, New York

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Sean Michael Kerwin, University of Texas, Austin, Texas

reproduction of these items for any other use. For permissions and

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other rights under this copyright, please contact BSCS, 5415 Mark

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info@bscs.org; (719) 531-5550.

NIH Publication No. 05-5170

ISBN: 1-929614-14-4

Contents

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v About the National Institutes of Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii About the National Center for Research Resources. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix Introduction to Using Technology to Study Cellular and Molecular Biology . . . . . . . . . . . . . . . . . . . . . 1

• What are the Objectives of the Module?

• Why Teach the Module?

• What’s in It for the Teacher?

Implementing the Module . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

• What Are the Goals of the Module?

• What Are the Science Concepts and How Are They Connected?

• Science Content of the Lessons

• Conceptual Flow of the Lessons

• How Does the Module Correlate to the National Science Education Standards?

– Content Standards: High School

– Teaching Standards

– Assessment Standards

• How Does the 5E Instructional Model Promote Active, Collaborative, Inquiry-Based Learning?

– Engage

– Explore

– Explain

– Elaborate

– Evaluate

• How Does the Module Support Ongoing Assessment?

• How Can Controversial Topics Be Handled in the Classroom?

Using the Student Lessons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

• Format of the Lessons

• Timeline for the Module

Using the Web Site. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

• Hardware/Software Requirements

• Downloading and Installing Macromedia Flash Player

• Getting the Most out of the Web Site

• Collaborative Groups

• Web Activities for Students with Disabilities

Information about Using Technology to Study Cellular and Molecular Biology . . . . . . . . . . . . . . . 23

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

2 Major Preconceptions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

3 Scale and Resolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

3.1 Scale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

3.2 Resolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

4 Major Techniques in the Study of Cellular and Molecular Biology . . . . . . . . . . . . . . . . . . . . 26

4.1 Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

4.2 X-ray crystallography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

4.3 Nuclear magnetic resonance (NMR) spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . 33

4.4 Laser technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

4.5 Simulations and computations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

5 Technology and the Origins of Molecular Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

6 The Goal of This Supplement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

Student Lessons

• Lesson 1— What Is Technology? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

• Lesson 2— Resolving Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

• Lesson 3— Putting Technology to Work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73

• Lesson 4— Technology: How Much Is Enough? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97

Masters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105

Foreword

This curriculum supplement, from The NIH

ties promote active and collaborative learning

Curriculum Supplement Series, brings cutting-

and are inquiry-based to help students develop

edge medical science and basic research dis-

problem-solving strategies and critical thinking.

coveries from the laboratories of the National

Institutes of Health (NIH) into classrooms.

Each curriculum supplement comes with a

As the largest medical research institution in

complete set of materials for both teachers and

the United States, NIH plays a vital role in the

students, including printed materials, exten-

health of all Americans and seeks to foster

sive background and resource information,

interest in research, science, and medicine-

and a Web site with interactive activities. The

related careers for future generations. NIH’s

supplements are distributed at no cost to teach-

Office of Science Education (OSE) is dedicated

ers across the United States. All materials may

to promoting science education and scientific

be copied for classroom use but may not be

literacy.

sold. We welcome feedback from our users.

For a complete list of curriculum supplements,

We designed this curriculum supplement to

updates, availability and ordering information,

complement existing life science curricula at

or to submit feedback, please visit our Web site

both the state and local levels and to be consis-

at http://science.education.nih.gov or write to

tent with National Science Education Standards.1

Curriculum Supplements Series

It was developed and tested by a team com-

Office of Science Education

posed of teachers, scientists, medical experts,

National Institutes of Health

and other professionals with relevant subject-

6705 Rockledge Dr., Suite 700 MSC 7984

area expertise from schools and institutes from

Bethesda, MD 20892-7984

across the country; and by NIH scientists and

curriculum-design experts from Biological Sci-

We appreciate the valuable contributions of the

ences Curriculum Study (BSCS), Edge Inter-

talented staff at BSCS, Edge Interactive, and

active, and SAIC. The authors incorporated

SAIC. We are also grateful to the NIH scientists,

real scientific data and actual case studies into

advisors, and all other participating profession-

classroom activities. A three-year development

als for their work and dedication. Finally, we

process included geographically dispersed field

thank the teachers and students who partici-

tests by teachers and students.

pated in focus groups and field tests to ensure

that these supplements are both engaging and

The structure of this module enables teachers

effective. I hope you find our series a valuable

to effectively facilitate learning and stimulate

addition to your classroom and wish you a pro-

student interest by applying scientific concepts

ductive school year.

to real-life scenarios. Design elements include a

conceptual flow of lessons based on BSCS’s 5E

Bruce A. Fuchs, Ph.D.

Instructional Model of Learning, multisubject

Director

integration emphasizing cutting-edge science

Office of Science Education

content, and built-in assessment tools. Activi-

National Institutes of Health

supplements@science.education.nih.gov

________________________

1 In 1996, the National Academy of Sciences released the National Science Education Standards, which outlines what all citizens should understand about science by the time they graduate from high school. The Standards encourages teachers to select major science concepts that empower students to use information to solve problems rather than stressing memoriza-tion of unrelated information.

v

About the National Institutes of Health

Begun as the one-room Laboratory of Hygiene

• biological effects of environmental contami-

in 1887, the National Institutes of Health (NIH)

nants;

today is one of the world’s foremost medical

• understanding of mental, addictive, and

research centers and the federal focal point for

physical disorders; and

health research in the United States.

• collection, dissemination, and exchange of

information in medicine and health, includ-

Mission and Goals

ing the development and support of medical

The NIH mission is science in pursuit of funda-

libraries and the training of medical librari-

mental knowledge about the nature and behav-

ans and other health information specialists.

ior of living systems and the application of that

knowledge to extend healthy life and reduce the

Organization

burdens of illness and disability. The goals of

Composed of 27 separate institutes and centers,

the agency are to

NIH is one of eight health agencies of the Pub-

• foster fundamental creative discoveries,

lic Health Service within the U.S. Department

innovative research strategies, and their

of Health and Human Services. NIH encom-

applications as a basis for advancing signifi-

passes 75 buildings on more than 300 acres in

cantly the nation’s capacity to protect and

Bethesda, Md., as well as facilities at several

improve health;

other sites in the United States. The NIH budget

• develop, maintain, and renew scientific

has grown from about $300 in 1887 to more

resources—both human and physical—that

than $27.8 billion in 2004.

will ensure the nation’s ability to prevent

disease;

Research Programs

• expand the knowledge base in medical and

One of NIH’s principal concerns is to invest

associated sciences in order to enhance the

wisely the tax dollars entrusted to it for

nation’s economic well-being and ensure a

the support and conduct of this research.

continued high return on the public invest-

Approximately 82 percent of the investment is

ment in research; and

made through grants and contracts support-

• exemplify and promote the highest level

ing research and training in more than 2,000

of scientific integrity, public accountability,

research institutions throughout the United

and social responsibility in the conduct of

States and abroad. In fact, NIH grantees are

science.

located in every state in the country. These

grants and contracts make up the NIH Extra-

NIH works toward meeting those goals by pro-

mural Research Program.

viding leadership, direction, and grant support

to programs designed to improve the health of

Approximately 10 percent of the budget goes to

the nation through research in the

NIH’s Intramural Research Programs, the more

• causes, diagnosis, prevention, and cure of

than 2,000 projects conducted mainly in its

human diseases;

own laboratories. These projects are central to

• processes of human growth and development;

the NIH scientific effort. First-rate intramural

vii

scientists collaborate with one another regard-

trious scientists and physicians. Among them are

less of institute affiliation or scientific discipline

115 winners of Nobel Prizes for achievements as

and have the intellectual freedom to pursue

diverse as deciphering the genetic code and iden-

their research leads in NIH’s own laboratories.

tifying the causes of hepatitis.

These explorations range from basic biology to

behavioral research, to studies on treatment of

Five Nobelists made their prize-winning discov-

major diseases.

eries in NIH laboratories. You can learn more

about Nobelists who have received NIH sup-

Grant-Making Process

port at http://www.nih.gov/about/almanac/nobel/

The grant-making process begins with an idea

index.htm.

that an individual scientist describes in a writ-

ten application for a research grant. The project

Impact on the Nation’s Health

might be small, or it might involve millions of

Through its research, NIH has played a major

dollars. The project might become useful imme-

role in making possible many achievements

diately as a diagnostic test or new treatment, or

over the past few decades, including

it might involve studies of basic biological pro-

• Mortality from heart disease, the number

cesses whose clinical value may not be apparent

one killer in the United States, dropped by

for many years.

36 percent between 1977 and 1999.

• Improved treatments and detection methods

Each research grant application undergoes peer

increased the relative five-year survival rate

review. A panel of scientific experts, primarily

for people with cancer to 60 percent.

from outside the government, who are active

• With effective medications and psychother-

and productive researchers in the biomedi-

apy, the 19 million Americans who suffer

cal sciences, first evaluates the scientific merit

from depression can now look forward to a

of the application. Then, a national advisory

better, more productive future.

council or board, composed of eminent scien-

• Vaccines are now available that protect

tists as well as members of the public who are

against infectious diseases that once killed

interested in health issues or the biomedical sci-

and disabled millions of children and adults.

ences, determines the project’s overall merit and

• In 1990, NIH researchers performed the

priority in advancing the research agenda of the

first trial of gene therapy in humans. Scien-

particular NIH funding institutes.

tists are increasingly able to locate, identify,

and describe the functions of many of the

About 38,500 research and training applications

genes in the human genome. The ultimate

are reviewed annually through the NIH peer-

goal is to develop screening tools and gene

review system. At any given time, NIH supports

therapies for the general population for can-

35,000 grants in universities, medical schools,

cer and many other diseases.

and other research and research training institu-

tions, both nationally and internationally.

For more information about NIH,

visit http://www.nih.gov.

NIH Nobelists

The roster of people who have conducted NIH

research or who have received NIH support over

the years includes some of the world’s most illus-

viii

About the National Center for

Research Resources

The National Center for Research Resources

NIH-supported investigators and others special-

(NCRR) is a component of the National Insti-

ized research environments that are profession-

tutes of Health (NIH), one of the world’s fore-

ally staffed, have state-of-the-art technologies

most biomedical research organizations. The

and Web-based networks, and provide col-

institutes and centers that compose NIH fund

laborative research opportunities. NCRR also

biomedical research to uncover new knowl-

supports networks of National Gene Vector Lab-

edge that will lead to better health for everyone

oratories and Human Islet Cell Resource Cen-

in the nation. Among the NIH institutes and

ters, a resource for normal and diseased human

centers, NCRR has a unique role. Rather than

tissue for research, and science education for

supporting studies of specific diseases or dis-

K−12 students and the public.

orders, NCRR supports programs that ensure

that essential tools, materials, specialized facili-

Comparative Medicine: Animal models and

ties, and resources for infrastructure and man-

colonies (mammalian and nonmammalian),

power development are accessible to biomedical

genetic stocks, and biological materials—such

researchers throughout the nation. In this way,

as cell lines, tissues, and organs—help meet

NCRR enables research in many areas of health

NIH-supported investigators’ resource needs. In

and complements the missions of the NIH

particular, the NCRR network of eight National

categorical institutes. NCRR’s diverse array of

Primate Research Centers is a valuable resource

resources is concentrated in four divisions:

for investigations of human health and disease.

Biomedical Technology Research and Research

Research Infrastructure: Diverse grant programs

Resources: A large network of Biomedical Tech-

help build, expand, and strengthen the nation’s

nology Resource Centers provides the research

biomedical research environment by developing

community nationwide with the newest and

research infrastructure and faculty capacity at

most advanced technologies and techniques.

minority institutions that award doctorates in

Core scientists at these centers collaborate in

the health or health-related sciences; improving

multidisciplinary investigations and train vis-

biomedical and behavioral research through an

iting researchers to apply these technologies

NIH-wide program of matching grants for con-

and techniques to basic and clinical studies. In

struction and renovation of research facilities;

addition, NCRR provides institutional grants to

and increasing competitiveness of institutions

purchase expensive state-of-the-art and high-

from states with limited NIH support.

end instrumentation to be used by a number of

investigators on a shared basis.

For more information about research resources

and resource-related funding opportunities, visit

Clinical Research Resources: A national network

the National Center for Research Resources Web

of General Clinical Research Centers offers

site at http://www.ncrr.nih.gov.

ix

Introduction to

Using Technology to Study

Cellular and Molecular Biology

The abilities to develop and use technology are

us and provides the foundation for improv-

inherent human characteristics. We recognize

ing our choices about our personal health and

problems and look for solutions. Technology

the health of our community. With this mod-

makes our lives easier and more comfortable.

ule, students experience how science provides

At the same time, critical research technolo-

evidence that can be used to understand and

gies have advanced scientific discovery. Where

treat human disease. The National Center for

scientists once gazed in awe at individual cells

Research Resources believes that education is an

and microorganisms, we now can view the elec-

important way to accomplish its mission, which

tron clouds of individual atoms and reconstruct

includes helping the public understand the

detailed three-dimensional structures of biologi-

importance of technology use and development

cal molecules, such as proteins, and biological

to health.

structures, such as ribosomes. As the depth and

breadth of scientific knowledge have increased,

The lessons in this module encourage students

human health and our quality of life have

to think about the relationships among knowl-

improved.

edge, choice, behavior, and human health in

this way:

What Are the Objectives of the Module?

Using Technology to Study Cellular and Molecu-

Knowledge (what is known and not known)

lar Biology has several objectives. The first is to

+ Choice = Power

help students understand that technology is a

means of solving a problem. As a consequence,

Power + Behavior = Enhanced Human Health

students realize that technologies affect all fac-

ets of our lives and that technology relates to

The final objective of this module is to encour-

more than computers.

age students to think in terms of these relation-

ships now and as they grow older.

The second objective is to allow students to

investigate how technology is used to deepen

Why Teach the Module?

and broaden our knowledge of cellular and

High school biology classes offer an ideal setting

molecular biology. Lessons in this module help

for integrating many areas of student interest.

students sharpen their skills in observation,

In this module, students participate in activities

critical thinking, experimental design, and data

that integrate inquiry science, human health,

analysis. They also make connections to other

mathematics, and the interweaving of science,

disciplines such as English, history, mathemat-

technology, and society. The real-life context

ics, and social science.

of the module’s classroom lessons is engaging

for students, and the knowledge gained can be

The third objective is to convey to students the

applied immediately to students’ lives.

purpose of scientific research. Ongoing research

affects how we understand the world around

“Lesson 3 was a great inquiry experience. Students

1

Using Technology to Study Cellular and Molecular Biology

enjoyed the activity and at the same time, learned

In addition, the module provides a means for

how to apply what they know about technology.

professional development. Teachers can engage

The scale activity really got students thinking

in new and different teaching practices like

about the size of the cell and what is in the cell.

those described in this module without com-

This was a wow activity.”—Field-Test Teacher

pletely overhauling their entire program. In

Designing Professional Development for Teachers

“The activities made us think. We figured out

of Science and Mathematics, the authors write

things ourselves, and we actually did stuff instead

that replacement modules such as this one

of just reading.”—Field-Test Student

“offer a window through which teachers get a

glimpse of what new teaching strategies look

What’s in It for the Teacher?

like in action.”16 By experiencing a short-term

Using Technology to Study Cellular and Molecu-

unit, teachers can “change how they think

lar Biology meets many of the criteria by which

about teaching and embrace new approaches

teachers and their programs are assessed.

that stimulate students to problem solve, rea-

• The module is standards based and meets

son, investigate, and construct their own mean-

science content, teaching, and assessment

ing for the content.” The use of a supplemental

standards as expressed in the National Sci-

unit such as this module can encourage reflec-

ence Education Standards. It pays particular

tion and discussion and stimulate teachers to

attention to the standards that describe

improve their practices by focusing on student

what students should know and be able to

learning through inquiry.

do with respect to scientific inquiry.

• It is an integrated module, drawing most

The following table correlates topics often

heavily from the subjects of science, social

included in the high school biology curriculum

science, mathematics, and health.

with the major concepts presented in this mod-

• The module has a Web-based technology

ule. This information is presented to help teach-

component on which there is an interactive

ers make decisions about incorporating this

database and simulations.

material into the curriculum.

• The module includes built-in assessment

tools, which are noted in each of the les-

If you have any questions about the supple-

sons with an assessment icon.

ment, please contact the NIH Office of Science

Education at supplements@science.education.

nih.gov.

2

Correlation of Using Technology to Study Cellular and Molecular Biology to High School Biology Topics

Topics

Lesson 1

Lesson 2

Lesson 3

Lesson 4

The development of new

technologies is continuous,

✔

✔

and the ability to develop

new technologies is char-

acteristic of humans.

Technology provides a

means of solving a

✔

✔

✔

✔

problem.

Biological structures differ

in size.

✔

Different technologies

are used to study biologi-

✔

✔

cal structures of different

sizes.

Biologists use microscopes

to study cells.

✔

✔

Proteins are important

biological molecules. Their

✔

✔

structure is related to their

function.

Science and technology

influence, and are influ-

✔

✔

enced by, society.

3

Introduction

Implementing the Module

The four lessons in this module are designed

What Are the Science Concepts and How

to be taught in sequence for approximately one

Are They Connected?

week as a replacement for a part of the standard

The lessons are organized into a conceptual

curriculum in high school biology. The follow-

framework that allows students to move from

ing pages offer general suggestions about using

what they already know about technology, some

these materials in the classroom; you will find

of which may be incorrect, to gaining a scien-

specific suggestions in the procedures provided

tific perspective on the nature of technology

for each lesson.

and its importance to science and to their lives.

Students begin learning about technology by

What Are the Goals of the Module?

developing their own definition of it and learn-

Using Technology to Study Cellular and Molecular

ing about scale ( What Is Technology? ). Students

Biology is designed to help students reach these

continue to explore the concept of scale and

major goals associated with scientific literacy:

investigate resolution ( Resolving Issues). An

• to understand a set of basic scientific prin-

investigation of how technologies can be used

ciples related to the nature and role of

to solve scientific problems related to human

technology in biological science and to the

health ( Putting Technology to Work) allows

effects of technology on human health;

students to gain a deeper understanding of

• to experience the process of scientific inquiry

technology’s importance to our lives. The final

and develop an enhanced understanding of the

lesson, Technology: How Much Is Enough? , allows

nature and methods of science;

students to consider the current state of tech-

• to recognize the role of science in society

nology and design new technologies to answer

and the relationship between basic science

questions of relevance to cellular and molecular

and human health; and

biology. The following two tables illustrate the

• to help prepare high school biology students

science content and conceptual flow of the class-

for the technological world they will inherit.

room lessons.

Science Content of the Lessons

Lesson

Science Content

Lesson 1

Technology; scale

Lesson 2

Resolution

Lesson 3

Microscopy; X-ray crystallography; using technology to understand and solve health-

related problems

Lesson 4

History of technology development; development of new technologies

5

Using Technology to Study Cellular and Molecular Biology

Conceptual Flow of the Lessons

Lesson

Learning Focus*

Major Concept

Lesson 1

Engage

Technology is a body of knowledge used to create tools,

What Is

Explore

develop skills, and extract or collect materials. It is also the

Technology?

Explain

application of science (the combination of the scientific

method and material) to meet an objective or solve a prob-

lem. Scale is a way to represent the relationship between the

actual size of an object and how that size is characterized,

either numerically or visually.

Lesson 2

Explore

It is important to identify the right tool (technology) for the

Resolving

Explain

job. An important consideration is technology’s ability to

Issues

resolve structural details of biological objects. Two objects

can be resolved if they are illuminated with radiation (that is,

a probe) of wavelength (that is, size) that is not larger than

the distance separating the objects. Generally, the smaller the

probe used, the greater the structural detail, or resolution,

that results. Detailed structural knowledge about biological

objects requires information obtained in three dimensions,

not just two.

Lesson 3

Explore

Technologies differ in their resolving capabilities, thus provid-

Putting

Explain

ing different information about an object. Solving a problem

Technology to

Elaborate

requires an appropriate technology or series of technologies.

Work

Technology provides valuable tools for solving scientific prob-

lems of relevance to human health.

Lesson 4

Evaluate

New technologies are developed, and old technologies are

Technology:

improved and refined, continuously. This must be done to

How Much Is

meet the demands created by new and existing problems.

Enough?

*See How Does the 5E Instructional Model Promote Active, Collaborative, Inquiry-Based Learning? on page 9.

How Does the Module Correlate to the

National Science Education Standards ( NSES).

National Science Education Standards?

The content of the module is explicitly stan-

Using Technology to Study Cellular

dards based. Each time a standard is addressed

and Molecular Biology supports

in a lesson, an icon appears in the margin along

you in your efforts to reform sci-

with the applicable standard. The following

ence education in the spirit of the

chart lists the specific content standards that

National Research Council’s 1996

this module addresses.

6

Content Standards: High School

Standard A:

Correlation to

As a result of activities in grades 9–12, all students should develop

Using Technology to

Study Cellular and

Molecular Biology

Abilities necessary to do scientific inquiry

• Identify questions and concepts that guide scientific investigations.

Lessons 1, 2, 3, 4

• Design and conduct a scientific investigation.

Lesson 3

• Use technology and mathematics to improve investigations and

Lessons 2, 3, 4

communications.

• Formulate and revise scientific explanations and models using logic

Lesson 3

and evidence.

• Recognize and analyze alternative explanations and models.

Lessons 1, 3

• Communicate and defend a scientific argument.

Lessons 3, 4

Understandings about scientific inquiry

• Scientists usually inquire about how physical, living, or designed

Lessons 3, 4

systems function.

• Scientists conduct investigations for a wide variety of reasons, such as Lesson 3

to discover new aspects of the natural world, to explain observed

phenomenon, or to test conclusions of prior investigations or predic-

tions of current theories.

• Scientists rely on technology to enhance gathering and manipulating

Lessons 2, 3, 4

data.

• Mathematics is essential in all aspects of scientific inquiry.

Lessons 1, 4

• Scientific explanations must adhere to criteria.

Lesson 3

• New knowledge and methods emerge from different types of investi-

Lessons 3, 4

gations and public communication among scientists.

Standard B:

As a result of their activities in grades 9–12, all students should

develop understanding of

Structure and properties of matter

• The physical properties of molecules are determined by the structure

Lesson 3

of the molecule.

Standard C:

As a result of their activities in grades 9–12, all students should

develop understanding of

The cell

• Cells have particular structures that underlie their functions.

Lesson 3

7

Implementing the Module

Using Technology to Study Cellular and Molecular Biology

Standard E:

As a result of their activities in grades 9–12, all students should

develop understanding of

Abilities of technological design

• Identify a problem or design an opportunity.

Lessons 1, 2, 3, 4

• Implement a proposed solution.

Lessons 2, 3

• Evaluate the solution and its consequences.

Lessons 2, 3, 4

• Communicate the problem, process, and solution.

Lessons 1, 2, 3, 4

Understandings about science and technology

• Many scientific investigations require contributions from different

Lessons 1, 2, 3, 4

disciplines, including engineering.

• Science often advances with new technologies.

Lessons 1, 4

• Creativity, imagination, and a good knowledge base are all required in Lessons 1, 4

the work of science and engineering.

• Scientific inquiry is driven by the desire to understand the natural

Lessons 1, 4

world, and technological design is driven by the need to meet human

needs and solve human problems.

Standard F:

As a result of their activities in grades 9–12, all students should

develop understanding of

Science and technology in local, national, and global challenges

• Science and technology are essential social enterprises.

Lessons 1, 4

• Progress in science and technology can be affected by social issues

and challenges.

Standard G:

As a result of their activities in grades 9–12, all students should

develop understanding of

Science as a human endeavor

• Individuals and teams have contributed and will continue to contribute Lessons 1, 2, 3, 4

to the scientific enterprise.

• Scientists have ethical traditions that value peer review, truthful

Lesson 3

reporting about methods and investigations, and making public the

results of work.

• Scientists are influenced by societal, cultural, and personal beliefs.

Lessons 1, 4

Science is a part of society.

Nature of scientific knowledge

• Science distinguishes itself form other ways of knowing and from

Lesson 3

other bodies of knowledge through the use of empirical standards,

logical arguments, and skepticism.

8

• Scientific explanations must meet certain criteria such as consistency

Lesson 3

and accuracy.

• All scientific knowledge is subject to change as new evidence

Lessons 1, 4

becomes available.

Teaching Standards

these opportunities for assessment and provide

The suggested teaching strategies in all the les-

answers to questions that can help you analyze

sons support you as you work to meet the teach-

student feedback.

ing standards outlined in the National Science

Education Standards. This module helps you plan

How Does the 5E Instructional Model

an inquiry-based science program by provid-

Promote Active, Collaborative, Inquiry-

ing short-term objectives for students. It also

Based Learning?

includes planning tools such as the Conceptual

Because learning does not occur through a pro-

Flow of the Lessons chart and the Suggested

cess of passive absorption, the lessons in this

Timeline for teaching the module. You can

module promote active learning. Students are

use this module to update your curriculum in

involved in more than listening and reading.

response to your students’ interest in this topic.

They are developing skills, analyzing and evalu-

The focus on active, collaborative, and inquiry-

ating evidence, experiencing and discussing, and

based learning in the lessons helps you support

talking to their peers about their own under-

the development of student understanding and

standings. Students work collaboratively with

nurture a community of science learners.

others to solve problems and plan investiga-

tions. Many students find that they learn better

The structure of the lessons in this module

when they work with others in a collaborative

enables you to guide and facilitate learning. All

environment than when they work alone in a

the activities encourage and support student

competitive environment. When all this active,

inquiry, promote discourse among students,

collaborative learning is directed toward inquiry

and challenge students to accept and share

science, students succeed in making their own

responsibility for their learning. Using the 5E

discoveries. They ask questions, observe, analyze,

Instructional Model, combined with active, col-

explain, draw conclusions, and ask new ques-

laborative learning, allows you to respond effec-

tions. These inquiry experiences include both

tively to the diversity of student backgrounds

those that involve students in direct experimenta-

and learning styles. The module is fully anno-

tion and those in which students develop expla-

tated, with suggestions for how you can encour-

nations through critical and logical thinking.

age and model the skills of scientific inquiry,

as well as foster the curiosity, openness to new

This view of students as active thinkers who

ideas and data, and skepticism that characterize

construct their own understanding out of inter-

successful study of science.

actions with phenomena, the environment, and

other individuals is based on the theory of con-

Assessment Standards

structivism. A constructivist view of learning

You can engage in ongoing assessment of your

recognizes that students need time to

teaching and of student learning using the vari-

• express their current thinking;

ety of assessment components embedded within

• interact with objects, organisms, substances,

the module’s structure. The assessment tasks are

and equipment to develop a range of experi-

authentic; they are similar to tasks that students

ences on which to base their thinking;

will engage in outside the classroom or in which

• reflect on their thinking by writing and

scientists participate. Annotations guide you to

expressing themselves and comparing what

9

Implementing the Module

Using Technology to Study Cellular and Molecular Biology

they think with what others think; and

• interact with materials and ideas through

• make connections between their learning

classroom and Web activities;

experiences and the real world.

• consider different ways to solve a problem or

answer a question;

This module provides a built-in structure for

• acquire a common set of experiences with

creating a constructivist classroom: the 5E

their classmates so they can compare results

Instructional Model. This model sequences the

and ideas;

learning experiences so that students have the

• observe, describe, record, compare, and

opportunity to construct their understanding of

share their ideas and experiences; and

a concept over time. The model takes students

• express their developing understanding of

through five phases of learning that are easily

technology by analyzing and interpreting

described using five words that begin with the

data and by answering questions.

letter E: Engage, Explore, Explain, Elaborate,

and Evaluate. The following paragraphs illus-

Explain

trate how the 5Es are implemented across the

The Explain lessons provide opportunities for

lessons in this module.

students to connect their previous experiences

and to begin to make conceptual sense of the

Engage

main ideas of the module. This stage also allows

Students come to learning situations with prior

for the introduction of formal language, scien-

knowledge. This knowledge may or may not

tific terms, and content information that might

be congruent with the concepts presented in

make students’ previous experiences easier to

this module. Engage lessons provide the oppor-

describe and explain.

tunity for teachers to find out what students

already know or think they know about the

In the Explain lessons in this module, Lesson 1:

topic and concepts to be covered.

What Is Technology? , Lesson 2: Resolving Issues,

and Lesson 3: Putting Technology to Work, students

The Engage lesson in this module, Lesson 1:

• explain concepts and ideas about technology

What Is Technology? , is designed to

(in their own words);

• pique students’ curiosity and generate interest;

• listen to and compare others’ explanations of

• determine students’ current understanding

their results with their own;

about technology;

• become involved in student-to-student dis-

• invite students to raise their own questions

course in which they explain their thinking

about technology;

to others and debate their ideas;

• encourage students to compare their ideas

• revise their ideas;

with the ideas of others; and

• record their ideas and current understanding;

• enable teachers to assess what students do

• use labels, terminology, and formal language;

or do not understand about the stated out-

and

comes of the lesson.

• compare their current thinking with what

they previously thought.

Explore

In the Explore portions of the module, Lesson

Elaborate

1: How Low Can You Go? (Activity 2), Les-

In the Elaborate lesson, Lesson 3: Putting Tech-

son 2: Resolving Issues, and Lesson 3: Putting

nology to Work, students apply or extend impor-

Technology to Work, students investigate scale,

tant concepts in new situations and relate their

resolution, and the utility of technology to solve

previous experiences to new ones. Students

scientific problems, including those relevant to

make conceptual connections between new and

human health. These lessons require students to

former experiences. In this lesson, students

make observations, evaluate and interpret data,

• connect ideas, solve problems, and apply

and draw conclusions. Students

their understanding in a new situation;

10

• use scientific terms and descriptions;

• demonstrate what they understand about

• draw reasonable conclusions from evidence

technology and how well they can apply

and data;

their knowledge to solve a problem;

• add depth to their understanding of con-

• share their current thinking with others;

cepts and processes; and

• assess their own progress by comparing

• communicate their understanding to others.

their current understanding with their prior

knowledge; and

Evaluate

• ask questions that take them deeper into a

The Evaluate lesson is the final stage of the

concept.

instructional model, but it only provides a

“snapshot” of what the students understand

To review the relationship of the 5E Instruc-

and how far they have come from where they

tional Model to the concepts presented in the

began. In reality, the evaluation of students’

module, see the Conceptual Flow of the Lessons

conceptual understanding and ability to use

chart, on page 6.

skills begins with the Engage lesson and contin-

ues throughout each stage of the instructional

When a teacher uses the 5E Instructional Model,

model, as described in the following section.

he or she engages in practices that are very dif-

Combined with the students’ written work and

ferent from those of a traditional teacher. In

performance of tasks throughout the module,

response, students also participate in their learn-

however, the Evaluate lesson can serve as a

ing in ways that are different from those experi-

summative assessment of what students know

enced in a traditional classroom. The following

and can do.

charts, What the Teacher Does and What the

Students Do, outline these differences.

The Evaluate lesson in this module, Lesson 4:

Technology: How Much Is Enough? , provides an

opportunity for students to

What the Teacher Does

Stage

That is consistent with

That is inconsistent with

the 5E Instructional Model

the 5E Instructional Model

Engage

• Piques students’ curiosity and

• Introduces vocabulary

generates interest

• Explains concepts

• Determines students’ current under-

• Provides definitions and answers

standing (prior knowledge) of a

• Provides closure

concept or idea

• Discourages students’ ideas and

• Invites students to express what they questions

think

• Invites students to raise their own

questions

Explore

• Encourages student-to-student

• Provides answers

interaction

• Proceeds too rapidly for students to make

• Observes and listens to the students sense of their experiences

as they interact

• Provides closure

• Asks probing questions to help

• Tells the students that they are wrong

students make sense of their

• Gives information and facts that solve the

experiences

problem

• Provides time for students to puzzle • Leads the students step-by-step to a

through problems

solution

11

Teacher Background

Implementing the Module

Using Technology to Study Cellular and Molecular Biology

Explain

• Encourages students to use their

• Neglects to solicit students’ explanations

common experiences and data from • Ignores data and information students

the Engage and Explore lessons to

gathered from previous lessons

develop explanations

• Dismisses students’ ideas

• Asks questions that help students

• Accepts explanations that are not

express understanding and

supported by evidence

explanations

• Introduces unrelated concepts or skills

• Requests justification (evidence) for

students’ explanations

• Provides time for students to com-

pare their ideas with those of others

and perhaps to revise their thinking

• Introduces terminology and alterna-

tive explanations after students

express their ideas

Elaborate

• Focuses students’ attention on con-

• Neglects to help students connect new

ceptual connections between new

and former experiences

and former experiences

• Provides definitive answers

• Encourages students to use what

• Tells students that they are wrong

they have learned to explain a new

• Leads students step-by-step to a solution

event or idea

• Reinforces students’ use of scientific

terms and descriptions previously

introduced

• Asks questions that help students

draw reasonable conclusions from

evidence and data

Evaluate

• Observes and records as students

• Tests vocabulary words, terms, and

demonstrate their understanding of

isolated facts

concept(s) and performance of skills • Introduces new ideas or concepts

• Provides time for students to com-

• Creates ambiguity

pare their ideas with those of others • Promotes open-ended discussion

and perhaps to revise their thinking

unrelated to the concept or skill

• Interviews students as a means of

assessing their developing under-

standing

• Encourages students to assess their

own progress

12

What the Students Do

Stage

That is consistent with

That is inconsistent with

the 5E Instructional Model

the 5E Instructional Model

Engage

• Become interested in and curious

• Ask for the “right” answer

about the concept/topic

• Offer the “right” answer

• Express current understanding of a

• Insist on answers or explanations

concept or idea

• Seek closure

• Raise questions such as, What do I

already know about this? What do

I want to know about this? How

could I find out?

Explore

• “Mess around” with materials and

• Let others do the thinking and exploring

ideas

(passive involvement)

• Conduct investigations in which they • Work quietly with little or no interaction observe, describe, and record data

with others (only appropriate when

• Try different ways to solve a problem exploring ideas or feelings)

or answer a question

• Stop with one solution

• Acquire a common set of experi-

• Demand or seek closure

ences so they can compare results

and ideas

• Compare their ideas with those of

others

Explain

• Explain concepts and ideas in their

• Propose explanations from “thin air” with

own words

no relationship to previous experiences

• Base their explanations on evidence • Bring up irrelevant experiences and

acquired during previous investiga-

examples

tions

• Accept explanations without justification

• Record their ideas and current

• Ignore or dismiss other plausible

understanding

explanations

• Reflect on and perhaps revise their

• Propose explanations without evidence to

ideas

support their ideas

• Express their ideas using appropriate

scientific language

• Compare their ideas with what scien-

tists know and understand

Elaborate

• Make conceptual connections

• Ignore previous information or evidence

between new and former experi-

• Draw conclusions from “thin air”

ences

• Use terminology inappropriately and

• Use what they have learned to

without understanding

explain a new object, event,

organism, or idea

• Use scientific terms and descriptions

• Draw reasonable conclusions from

evidence and data

• Communicate their understanding to

others

13

Implementing the Module

Using Technology to Study Cellular and Molecular Biology

Evaluate

• Demonstrate what they understand

• Disregard evidence or previously accepted

about the concept(s) and how well

explanations in drawing conclusions

they can implement a skill

• Offer only yes-or-no answers or mem-

• Compare their current thinking with

orized definitions or explanations as

that of others and perhaps revise

answers

their ideas

• Fail to express satisfactory explanations in

• Assess their own progress by com-

their own words

paring their current understanding

• Introduce new, irrelevant topics

with their prior knowledge

• Ask new questions that take them

deeper into a concept or topic area

How Does the Module Support Ongoing

How Can Controversial Topics Be Handled

Assessment?

in the Classroom?

Because teachers will use this module in a vari-

Teachers sometimes feel that the discussion of

ety of ways and at a variety of points in the

values is inappropriate in the science classroom

curriculum, the most appropriate mechanism

or that it detracts from the learning of “real” sci-

for assessing student learning is one that occurs

ence. The lessons in this module, however, are

informally at various points within the four les-

based on the conviction that there is much to

sons, rather than something that happens more

be gained by involving students in analyzing

formally just once at the end of the module.

issues of science, technology, and society. Society

Accordingly, integrated within the four lessons

expects all citizens to participate in the demo-

in the module are specific assessment compo-

cratic process, and our educational system must

nents. These “embedded” assessment oppor-

provide opportunities for students to learn to deal

tunities include one or more of the following

with contentious issues with civility, objectivity,

strategies:

and fairness. Likewise, students need to learn that

• performance-based activities (for example,

science intersects with life in many ways.

developing graphs or participating in a dis-

cussion of health effects or social policies);

In this module, students have a variety of oppor-

• oral presentations to the class (for example,

tunities to discuss, interpret, and evaluate basic

presenting experimental results); and

science and health issues, some in the light of

• written assignments (for example, answer-

values and ethics. As students encounter issues

ing questions or writing about demonstra-

about which they feel strongly, some discus-

tions).

sions might become controversial. How much

controversy develops will depend on many fac-

These strategies allow the teacher to assess a

tors, such as how similar the students are with

variety of aspects of the learning process, such

respect to socioeconomic status, perspectives,

as students’ prior knowledge and current under-

value systems, and religious preferences. In addi-

standing, problem-solving and critical-thinking

tion, the language and attitude of the teacher

skills, level of understanding of new informa-

factor into the flow of ideas and the quality of

tion, communication skills, and ability to syn-

exchange among the students.

thesize ideas and apply understanding to a new

situation.

The following guidelines may help you facilitate

discussions that balance factual information

An assessment icon and an anno-

with feelings.

tation that describes the aspect of

• Remain neutral. Neutrality may be the single

learning that teachers can assess

most important characteristic of a successful

appear in the margin beside each

discussion facilitator.

step in which embedded assessment occurs.

• Encourage students to discover as much

14

information about the issue as possible.

see whether other students recognize the

• Keep the discussion relevant and moving

inappropriate comment and invite them to

forward by questioning or posing appropri-

respond.

ate problems or hypothetical situations.

• Create a sense of freedom in the classroom.

Encourage everyone to contribute, but do

Remind students, however, that freedom

not force reluctant students to enter the dis-

implies the responsibility to exercise that

cussion.

freedom in ways that generate positive

• Emphasize that everyone must be open to

results for all.

hearing and considering diverse views.

• Insist upon a nonhostile environment in the

• Use unbiased questioning to help the stu-

classroom. Remind students to respond to

dents critically examine all views presented.

ideas instead of to the individuals presenting

• Allow for the discussion of all feelings and

those ideas.

opinions.

• Respect silence. Reflective discussions often

• Avoid seeking consensus on all issues. The

are slow. If a teacher breaks the silence, stu-

multifaceted issues that the students dis-

dents may allow the teacher to dominate the

cuss result in the presentation of divergent

discussion.

views, and students should learn that this is

• At the end of the discussion, ask the stu-

acceptable.

dents to summarize the points that they and

• Acknowledge all contributions in the same

their classmates have made. Respect students

evenhanded manner. If a student seems to

regardless of their opinion about any contro-

be saying something for its shock value,

versial issue.

15

Implementing the Module

Using the Student Lessons

The heart of this module is a set of four class-

• Web-Based Activities tells you which of the

room lessons that allow students to discover

lesson’s activities use the Using Technology

important concepts related to technology and

to Study Cellular and Molecular Biology Web

its role in developing our understanding of cel-

site as the basis for instruction.

lular and molecular biology. To review these

• Photocopies lists the paper copies and

concepts in detail, refer to the Conceptual Flow

transparencies that need to be made from

of the Lessons chart, on page 6.

masters that are provided after Lesson 4, at

the end of the module.

Format of the Lessons

• Materials lists all items other than photo-

As you review the lessons, you will find that all

copies needed for the activities in the lesson.

contain common major features.

• Preparation outlines what you need to do to

be ready to teach the activities in the lesson.

At a Glance offers a convenient summary of the

lesson.

Procedure provides a step-by-step approach

• Overview provides a short summary of stu-

for conducting each activity in the classroom.

dent activities.

It includes implementation suggestions and

• Major Concepts presents the central ideas

answers to discussion questions.

that the lesson is designed to convey.

• Objectives lists specific understandings or

Within the Procedure section, annotations pro-

abilities students should derive from com-

vide additional commentary.

pleting the lesson.

• Tip from the field test details suggestions

• Teacher Background specifies which por-

from field-test teachers for teaching strate-

tions of the background section, Information

gies, class management, and module imple-

about Using Technology to Study Cellular and

mentation.

Molecular Biology, relate directly to the les-

• Assessment provides strategies for gauging

son. This reading material provides the sci-

student progress throughout the module,

ence content that supports the key concepts

and is identified by an assessment icon (see

covered in the lesson. The information

page 18).

provided is not intended to form the basis

• Icons identify specific annotations:

of lectures to students nor is it intended

as a direct resource for students. Rather, it

identifies teaching strategies that

enhances your understanding of the content

address specific science content

so that you can facilitate class discussions,

standards as defined by the National

answer student questions, and provide addi-

Science Education Standards.

tional examples.

identifies when to use the Web site

In Advance provides instructions for collecting

as part of the teaching strategy.

and preparing materials required to complete

Instructions in the Procedure sec-

the activities in the lesson.

tion tell you how to access the Web

17

Using Technology to Study Cellular and Molecular Biology

site and the relevant activity. Infor-

each activity and includes icons that denote

mation about using the Web site can

where in each activity masters, transparencies,

be found in Using the Web Site (see

and the Web site are used. The lesson organizer

page 19). A print-based alternative

is intended to be used only after you become

to each Web activity is provided for

familiar with the lesson materials. It can be a

classrooms in which Internet access

handy resource during lesson preparation as

is not available.

well as during classroom instruction.

identifies a print-based alternative

Masters to be photocopied are found after Les-

to a Web-based activity to be used

son 4, at the end of the module.

when computers are not available.

Timeline for the Module

identifies when assessment is

The timeline below outlines the optimal plan

embedded in the module’s structure.

for completing the four lessons in this module.

An annotation suggests strategies

The plan assumes you will teach the activities

for assessment.

on consecutive days. If your class requires more

time for discussing issues raised in this module

Lesson Organizer provides a brief summary

or for completing activities, adjust your time-

of the lesson. It outlines procedural steps for

line accordingly.

Suggested Timeline

Timeline

Activity

3 weeks ahead

Reserve computers

Check performance of Web site

1 week ahead

Make photocopies and transparencies

Gather materials

Day 1

Lesson 1

Monday

Activity 1: Technology—What’s It All About?

Activity 2: Searching for Scale

Day 2

Lesson 2

Tuesday

Activity 1: Probing for Answers

Activity 2: More than Meets the Eye

Day 3

Lesson 3

Wednesday

Activity 1: Putting Technology to Work;

Part 1, some of Part 2

Day 4

Part 2 (conclude), Part 3, and Part 4 (print version only)

Thursday

Day 5

Lesson 4

Friday

Activity 1: Time Travel

Activity 2: Is That All There Is?

Day 6

Activity 2: Is That All There Is? (conclude)

Monday

18

Using the Web Site

The Using Technology to Study Cellular and

puters. Links to download the Macromedia

Molecular Biology Web site is a wonderful tool

Flash plug-in are provided on the Web site’s

that can engage student interest in learning,

Getting Started page. This plug-in is required for

enhance the student’s learning experience,

the activities to function properly. The recom-

and orchestrate and individualize instruction.

mended hardware and software requirements

The Web site features simulations that articu-

for using the Web site are listed in table below.

late with two of this unit’s lessons. To access

Although your computer configuration may dif-

fer from those listed, the Web site may still be

the Web site, type the following URL into

functional on your computer. The most impor-

your browser: http://science.education.nih.gov/

tant items in this list are current browsers and

supplements/technology/student. Click on the

plug-ins.

link to a specific lesson under Web Portion of

Student Activities. If you do not have computer

or Internet access, you can use the print-based

Downloading and Installing Macromedia

alternative provided for each Web activity. Text

Flash Player

pertaining only to Web-based activities is lightly

To experience full functionality of the Web site,

shaded.

Macromedia Flash Player, version 6.0 or higher,

must be downloaded and installed on the hard

Hardware/Software Requirements

drive of each computer that will be used to

The Web site can be accessed from Apple

access the site. The procedure for downloading

Macintosh and IBM-compatible personal com-

and installing Macromedia Flash Player is out-

lined below.

Recommended Hardware/Software Requirements for Using the Web Site*

CPU/Processor (PC Intel, Mac)

Pentium III, 600 MHz; or Mac G4

Operating system (DOS/Windows, Mac OS)

Windows 2000 or higher; or Mac OS 9 or newer

System memory (RAM)

256 MB

Screen setting

1024 × 768 pixels, 32 bit color

Browser

Netscape Communicator 7.1 or Microsoft Internet

Explorer 6

Browser settings

JavaScript Enabled

Free hard drive space

10 MB

Connection speed

56 kbps modem or high-speed Internet connection

Plug-ins, installed for your Web browser

Macromedia Flash Plug-In, version 6 or better; or

Apple QuickTime Plug-In, version 6 or better

Audio

Sound card with speakers

*For users of screen-reader software, a multichannel sound card such as Sound Blaster® Live!™ is recommended.

19

Using Technology to Study Cellular and Molecular Biology

• Open a Web browser.

actual real-life experience than print-based

• Access the main page of the Web site at

resources can offer;

http://science.education.nih.gov/supplements/

• provide teachers with support for experi-

technology/teacher.

menting with new instructional approaches

• Click on the “Getting Started” section.

that allow students to work independently or

• Click on the link to “Macromedia Flash.”

in small teams and that give teachers increased

This will bring up the Macromedia Flash

credibility among today’s technology-literate

Player Download Center Web site.

students; and

• The Download Center Web site should

• increase teachers’ productivity by helping

present you with the option of installing the

them with assessment, record keeping, and

latest version (highest number) of Macro-

classroom planning and management.

media Flash Player. As of August 2004, this

should be at least version 7.0.

The ideal use of the Web site requires one com-

• Click on the button marked “Install Now,” or

puter for each student team. However, if you

“Download Now.” Clicking this button will

have only one computer available, you can still

allow Macromedia’s Web site to download and

use the Web site. For example, you can use a

install Flash Player on your computer’s hard

projection system to display the monitor image

drive. If you are using Internet Explorer, the

for the whole class to see. Giving selected stu-

installation will happen automatically after

dents in the class the opportunity to manipulate

clicking the “Install Now” button. If you are

the Web activities in response to suggestions

using Netscape, you will have to download

from the class can give students some of the

and run the installation file. Follow the on-

same autonomy in their learning that they

screen instructions provided.

would gain from working in small teams. Alter-

• Your Web browser may present you with

natively, you can rotate student teams through

a Security Dialog Box asking if you would

the single computer station.

like to install and run Macromedia Flash

Player. Click “Yes.”

Collaborative Groups

• After a minute or so, you should once again

Many of the activities in the lessons are

see the Macromedia Download Center Web

designed to be completed by teams of students

page on your browser. There will be a box

working together. Although individual students

toward the top of the page containing click-

working alone can complete these activities,

able text. The appearance of this box in

this strategy will not stimulate the types of

your browser window indicates that you

student-student interactions that are part of

have successfully downloaded and installed

active, collaborative, inquiry-based learning.

Macromedia Flash Player.

Therefore, we recommend that you organize

collaborative teams of two to four students

Getting the Most out of the Web Site

each, depending on the number of computers

Before you use the Web site, or any other piece

available. Students in teams larger than this will

of instructional software in your classroom, it

have difficulty organizing student-computer

may be valuable to identify some of the benefits

interactions equitably. This can lead to one or

you can expect the software to provide. Well-

two students’ assuming the primary responsibil-

designed instructional multimedia software can

ity for the computer-based work. Although this

• motivate students by helping them enjoy

type of arrangement can be efficient, it means

learning and want to learn more because

that some students will not have the opportu-

it enlivens content that students otherwise

nity to experience the in-depth discovery and

might find uninteresting;

analysis that the Web site was designed to stim-

• offer unique instructional capabilities

ulate. Team members not involved directly may

that allow students to explore topics in

become bored or disinterested.

greater depth and in ways that are closer to

20

We recommend that you keep students in the

Web Activities for Students with

same collaborative teams for all the activities

Disabilities

in the lessons. This will allow each team to

The Office of Science Education (OSE) is com-

develop a shared experience with the Web site

mitted to providing access to the Curriculum

and with the ideas and issues that the activities

Supplement Series for individuals with dis-

present. A shared experience will also enhance

abilities, including members of the public and

your students’ perceptions of the lesson as a

federal employees. To meet this commitment,

conceptual whole.

we will comply with the requirements of Sec-

tion 508 of the Rehabilitation Act. Section 508

If your student-to-computer ratio is greater than

requires that individuals with disabilities who

four to one, you will need to change the way

are members of the public seeking these materi-

you teach the module from the instructions in

als will have access to and use of information

the lessons. For example, if you have only one

and data that are comparable to those provided

computer available, you may want students to

to members of the public who are not individu-

complete the Web-based work over an extended

als with disabilities. The online versions of this

time period. You can do this several ways. The

series have been prepared to comply with Sec-

most practical way is to use your computer

tion 508.

as a center along with several other centers at

which students complete other activities. In this

If you use assistive technology (such as a Braille

approach, students rotate through the computer

reader or a screen reader) and the format of

center, eventually completing the Web-based

any material on our Web sites interferes with

work you have assigned.

your ability to access the information, please let

us know. To enable us to respond in a manner

A second way to structure the lessons if you

most helpful to you, please indicate the nature

have only one computer available is to use a

of your accessibility problem, the format in

projection system to display the desktop screen

which you would like to receive the material,

for the whole class to view. Giving selected stu-

the Web address of the requested material, and

dents in the class the opportunity to manipulate

your contact information.

the Web activities in response to suggestions

from the class can give students some of the

Contact us at

same autonomy in their learning they would

Curriculum Supplement Series

have gained from working in small teams.

Office of Science Education

National Institutes of Health

6705 Rockledge Drive, Suite 700 MSC 7984

Bethesda, MD 20892-7984

supplements@science.education.nih.gov

21

Using the Web Site

Using the

Using T Web Site

echnology to Study Cellular and Molecular Biology

Using Technology to Study Cellular and Molecular Biology 508-Compliant Web Activities Lesson

For Students with Hearing

For Students with Sight Impairment

Impairment

Lesson 2, both activi- No special considerations are required. There is no equivalent alternative to these ties

activities for students with sight impair-

ments. Students should be involved in the

group discussions of these activities and

be asked for their perspective.

Supervision is recommended.

Lesson 3, Parts 1

No special considerations are required. Students using screen-magnification or

and 3

screen-reading software can choose an

alternate, text-based version of the activ-

ity. The content of the alternate activity is

equivalent to the original’s, but it’s in a text

format. The activity is based on the print

version of the lesson. Images within the

reference manual are kept to a minimum.

The print version of the activity should be

kept handy for reference.

Note: Students using a screen magni-

fier may prefer the original version of the

activity.

When the activity loads, students press a

button to proceed to the original version

or the screen-reader-friendly version of the

activity.

Use the “Teacher Administration” link to

generate login codes for your students.

You will need one code for each student

using this version of the activity. You may

request up to 100 codes at one time.

The “Progress Map” at the bottom of each

page keeps track of each student’s prog-

ress. If a student closes the activity and

returns later, he will resume where he left

off. The last page of the activity provides a

summary of all the student’s answers. To

edit their responses, students can use the

Progress Map to return to any page they

have completed.

The computer the students use must be

linked to a printer.

Supervision is recommended.

Lesson 3, Part 2

No special considerations are required. This activity has been incorporated into

the print version of Lesson 3.

22

2

Information about Using

Technology to Study Cellular

and Molecular Biology

1 Introduction

scientific community in 1985. Biology teach-

For society to gain the most from technology,

ers became aware of the technique through

the public must be able to understand scientific

stories in the media and wanted to learn more

issues and consider them rationally. This point

about it. It was not until 1990, however, when

is made in the National Science Education Stan-

PCR inventor Kary Mullis published an article

dards: “Because molecular biology will continue

about the technique in Scientific American, that

into the 21st century as a major frontier of sci-

teachers found an accessible treatment of this

ence, students should understand the chemi-

important technology. It took another few years

cal basis of life, not only for its own sake, but

for PCR to be mentioned in most high school

because of the need to take informed positions

biology textbooks. This curriculum supplement,

on some of the practical and ethical implica-

Using Technology to Study Cellular and Molecu-

tions of humankind’s capacity to tinker with the

lar Biology, will help short-circuit the usually

fundamental nature of life.”

lengthy process by which technology makes its

way to the classroom.

A molecular genetic perspective affords teach-

ers an opportunity to help integrate many of

2 Major Preconceptions

biology’s subdisciplines. This integrative process

Preconception 1. Study in one field proceeds

began with the advent of recombinant-DNA

without contributions from, or connections to,

technology and is now being propelled by the

other fields.

new areas of bioinformatics and genomic biol-

This belief occurs, in part, because scientific

ogy. According to the National Science Education

disciplines are treated as isolated subjects in

Standards, molecular and evolutionary biology

most schools. Most science educators, however,

are among the “small number of general prin-

recognize the many connections among biol-

ciples that can serve as the basis for teachers

ogy, chemistry, and physics, and understand

and students to develop further understanding

the need for an integrated approach to science

of biology.” A similar point is made in a medi-

teaching. For example, molecular biology is a

cal context by the new Standards for Technol-

hybrid discipline, drawing upon concepts and

ogy Literacy, which recognizes that “the use of

techniques from physics, chemistry, and biology.

technology has made numerous contributions

This hybrid nature explains in part why high

to medicine over the years. Scientific and tech-

school students may find the study of molecular

nological breakthroughs are at the core of most

biology challenging. They are confronted by a

diagnostic and treatment practices.”12

science that is abstract and seems far removed

from classical biology. Moreover, many students

When teachers try to relate advances in tech-

are introduced to the subject at a point in their

nology to biology, they may be frustrated by

education where they have yet to take a formal

the fact that there is a lag, measured in years,

course in either chemistry or physics. Without

between scientific advance and its inclusion in

this scientific foundation, they are ill-prepared

the curriculum. For example, the polymerase

to undertake the study of life at its most funda-

chain reaction (PCR) was introduced to the

mental level.

23

Using Technology to Study Cellular and Molecular Biology

Preconception 2. Most of what students are

Preconception 4. Structure and function are

exposed to in science classes is about science,

independent and unrelated concepts.

not technology.

This supplement can build a foundation to

Additionally, technology is about computers

address this preconception and to help students

rather than about a way of adapting or a pro-

understand the interdependence of structure

cess for solving a problem. It is important for

and function. With this supplement, students

students to learn that each of the technologies

will explore concepts to help them under-

covered in this supplement is a tool applied to a

stand that technologies provide scientists with

specific task. The supplement will help students

essential information about structure. The

recognize the type of scientific information that

relationship between structure and function

can be obtained from various techniques and

may be easier for students to understand at a

gain an appreciation for and an understanding

macroscopic level, and students may struggle to

of the role technology has played in advancing

understand this relationship at the abstract level

our understanding of biological systems.

of molecules. Inquiry-based activities will allow

students to learn what structure is and at how

Preconception 3. Students are likely to have pre-

many levels structure can be defined. Through

conceptions about the contributions that a range

these activities, students will learn how devel-

oping structural information at various tiers

of technologies has made to science and medi-

provides increasingly greater information about

cine, that is, about the problem-solving capacity

function. Structure-function relationships are

of technology.

critical to understanding normal cellular pro-

For example, students have probably looked at

cesses, as well as those associated with disease.

a specimen with a light microscope, and they

Such intimate knowledge of biomolecules

have seen photomicrographs in textbooks.

promises to expand the range of drug targets,

However, students have limited experience

shift the discovery effort from direct screen-

evaluating the information conveyed at the

ing programs to rational target-based drug

microscopic level and placing it in the proper

design, and usher in a new era of personalized

context. Consequently, it will be important in

medicine. One of the activities that follows—in

this supplement to help students gain a per-

Lesson 3, Putting Technology to Work—gives stu-

spective of the relative sizes of cellular and

dents insight into these scientific developments.

molecular structures. The concepts of resolu-

tion and scale can help students appreciate that

3 Scale and Resolution

structures invisible to the unaided eye, such

3.1 Scale

as mitochondria, ribosomes, viruses, and pro-

How big is “big”? How small is “small”? It

tein molecules, have vastly different sizes and

depends, of course, on one’s point of refer-

require different technologies for study. It is

ence. An insect such as a bee (about 12 mm in

important that this supplement help students

length) is very small compared with a human

understand the need to obtain information from

(perhaps 1.7 to 2 meters in height). However, a

more than one technique to solve a problem.

bee is very large compared with one of the pol-

len grains it gathers (about 30 µm, or 0.03 mm,

in diameter). While it may be easy to discern

The concepts of resolution and scale

the relative sizes of some objects, such as those

can help students appreciate that struc-

we can see with the naked eye, it is far more

tures invisible to the unaided eye, such

difficult to imagine the size of things that are

as mitochondria, ribosomes, viruses,

very large or very small. For instance, how large

and protein molecules, have vastly dif-

is a lightyear? Can we conceive of the difference

ferent sizes and require different tech-

between 10 lightyears and 100 lightyears? What

nologies for study.

is the distance across a cell? A virus? A protein

24

Figure 1. Size of some familiar objects and energy waves on a logarithmic scale.

molecule? How much larger are these than the

in understanding how living systems function.

distance between two adjacent carbon atoms

How do muscles contract? How do enzyme

in a sugar molecule? Importantly, where do we

reactions occur? How are metabolic pathways

humans fit into the picture?

regulated? How are molecules transported from

one site to another? How do antibodies recog-

To understand the continuum from small to

nize antigens? We want answers to so many

large, we need a way to represent the relation-

questions related to how living systems func-

ship between the actual size of an object (for

tion that require us to understand molecular

example, its length or mass) and how that size

structure first. Why? A molecule’s function is

is characterized either numerically or visu-

determined by and is dependent on its struc-

ally. We need a scale, a series of ascending and

ture. So, how do we get information about the

descending steps to assess the relative or abso-

structure of biological molecules? Consider the

lute size of some property of an object. Scales

following:

can have upper and lower values, as required.

They may be linear, or, when the distance

As we look down a street in a residential neigh-

between upper and lower values is very large,

borhood, we note individual houses because

they may be logarithmic. Figure 1 presents the

we are capable of distinguishing the space

size of some familiar objects and energy waves

between the houses. We accomplish this feat

on a logarithmic scale.

using our visual system to detect visible light.

In other words, visible light is the probe we

Without some notion of scale, a water molecule

use to resolve these discrete structures. In a

might appear to be as large as a house if both

general sense, we can think of resolving power

are drawn to occupy the same physical space on

as a measure of the ability of a system to form

a piece of paper.

separate and distinct images of two objects of

a given angular separation. This relationship is

3.2 Resolution

derived from the laws of optics. What does this

In cellular and molecular biology, we are inter-

mean to the study of cellular and molecular

ested in resolving structural details of organs

biology? In the laws of optics, two objects can

and tissues at the cellular level, of the intrica-

be resolved if they are illuminated with radia-

cies that form the intracellular environment,

tion of wavelength that is not larger than the

of the molecules that make up living systems,

distance separating the objects. Visible light

and of molecular interactions. We are interested

has a wavelength of 4,000 to 7,000 angstroms

25

Information about Using Technology to Study Cellular and Molecular Biology Using Technology to Study Cellular and Molecular Biology

(Å; 1 Å = 10–8 cm = 10–10 m), or 4 to 7 × 10–7

a brief survey of some technologies important

m, and is a great probe for viewing a portion

to the study of cellular and molecular biology.

of our world. We can resolve much with the

It presents a sampling of current research in

naked eye and even more, such as cells and cell

cellular and molecular biology, showing that

organelles, with a light microscope. However,

techniques that have been around for decades

its wavelength makes it unusable as a probe for

continue to be refined and put to new uses,

resolving much smaller objects, such as mol-

sometimes in combination with other tech-

ecules and atoms. Other probes with smaller

niques.

wavelengths are required for this task.

4.1 Microscopy

4 Major Techniques in the Study of

The development of the microscope allowed us

Cellular and Molecular Biology

to extend our view to things not visible to the

There is a reciprocal relationship between tech-

naked eye. Consider what our view of biologi-

nology and the process of science. Improve-

cal systems would be if we had no knowledge

ments in technology enable scientists to

of cells and cell structure. Figure 2 depicts the

investigate questions that were previously dif-

development of three major types of microscopy

ficult, or even impossible, to address. At the

over time.

same time, scientific curiosity often provides

the impetus for refining an existing technology

The line for each type of microscopy shows

or developing a new one. This section provides

how improvements in technology have

Figure 2. Development and resolution of three major types of microscopy over time.

26

increased the resolution available with each

pighi proved the controversial theory that blood

technique. Higher resolution means being able

circulates in a circular motion from the heart

to see smaller objects.

around the body and back to the heart. Also

about this time, Robert Hooke is credited with

discovering the cell, the basic unit of life. Anto-

nio van Leeuwenhoek improved the lenses used

in microscopes, allowing an increase in maxi-

mum magnification from 50× to 200×. Because

of this, Leeuwenhoek was the first scientist

to view bacteria, protozoa, and sperm cells.

There were additional improvements to opti-

cal microscopy over the next 200 to 300 years,

which ultimately allowed optical microscopes to

distinguish objects as small as 200 nanometers

(nm; 2 × 10–7 m). This resolution is a physical

limit dictated by the wavelength of light (see

section 3.2).

Electron microscopy. The first electron micro-

scope was built in 1933 by Ernst Ruska, who

was awarded the 1986 Nobel Prize in Phys-

Figure 3. Optical microscope.

ics for his achievements in electron optics. To

break the 200-nm optical-resolution barrier,

Optical microscopy. The first microscopes were

Ruska used accelerated electrons instead of

optical microscopes, which used glass lenses

light and magnetic coils instead of glass lenses

to focus and magnify light. The first optical

to make an image. Electrons have a wavelength

microscope was constructed around 1695 by

that is 104 to 105 times smaller than the wave-

Hans and Sacharias Janssen, but it wasn’t until

length of light. This allows electron micro-

60 to 80 years later that major discoveries were

scopes to resolve objects that are 103 times

made with this technology. By viewing capillar-

smaller than the smallest resolvable object in a

ies under a microscope in 1660, Marcello Mal-

light microscope.

Figure 4. Resolution of three major types of microscopes.

27

Information about Using Technology to Study Cellular and Molecular Biology

Using Technology to Study Cellular and Molecular Biology

Interestingly, although the design and physi-

cal appearance of electron microscopes have

changed over the years, the essential character-

istics remain the same. All electron microscopes

require a high vacuum in which to form an

electron beam and high voltage to control this

beam. Electromagnetic lenses then focus the

electron beam onto the specimen and viewing

screen.

Figure 5 shows a typical transmission elec-

tron microscope (TEM). Note the much larger

physical size compared with a standard light

microscope, which fits comfortably on a labo-

ratory bench. TEMs are patterned after stan-

dard transmission light microscopes and yield

similar information about the size, shape,

and arrangement of particles that make up a

specimen, albeit at much higher resolution and

with a magnification range of about 1,000× to

300,000×.

Figure 6. High-resolution TEM.

Figure 5. A typical transmission electron micro-

scope (TEM).

The state-of-the-art TEM is the high-resolution

TEM (Figure 6), which can magnify a sample

up to 50,000,000 times and provide a resolution

of 0.1 nm. It can produce information that com-

Figure 7. Scanning electron microscope.

plements data obtained from X-ray techniques

(see section 4.2).

28

In addition to the TEM, the other most com-

moving through the cell interior, can create a

mon electron microscope is the scanning elec-

chemical map of the cell. One disadvantage of

tron microscope (SEM; Figure 7). The SEM

the technique is that it takes many minutes to

provides information about the surface features

produce an image, which limits its ability to

of an object. We learn about an object’s appear-

visualize rapid changes within the cell.

ance, texture, and detectable features to within

a resolution of several nanometers. Interest-

Another technique, called Fourier transform

ingly, we do not learn this information by view-

infrared microspectroscopy (FTIR) combines

ing biological specimens directly. Biological

microscopy with spectroscopy to provide

specimens have low contrast and are difficult

chemical information about the sample being

to see in the SEM. Consequently, high-contrast

visualized. Samples can be analyzed wet or

heavy atoms, such as osmium, are used to stain

dry, in air, at room temperature, and at normal

specimens and provide an indirect image of the

pressure. FTIR is limited for analysis of living

underlying biological structures.

specimens because samples must be very thin.

It has proven useful in studies of pathogenesis,

Resolution can be improved by modifica-

however. Biochemical studies of disease often

tions of the sample-preparation procedure. In

fail to detect chemical compounds associ-

a technique called cryo-electron microscopy

ated with pathology because the chemicals are

(cryo-EM), specimens are rapidly frozen with-

diluted during their analysis. FTIR can be used

out formation of ice crystals that can distort

to pinpoint areas of disease and identify com-

the specimen’s structure. It is then possible to

pounds in individual cells, providing insights

construct two- and three-dimensional models

into disease progression. The technique is cur-

of the sample by using a computer program

rently being developed for objective evaluations

that averages many electron micrographs taken

of pap smears.

from different angles. When the technique was

first applied to the structure of the ribosome in

1991, the resolution was just 45 Å. Still, it was

possible to see the two ribosome subunits and

the triangular space between them. In recent

years, scientists have used cryo-EM techniques

to image the ribosome to 4 Å.6–8 Studies with

these techniques have revealed the surface

topography of the ribosome for the first time

and helped crystallographers interpret the ribo-

some’s diffraction patterns.

Other microscopic techniques. Despite the long

history of light microscopy, it is still being

improved. For example, a new way to image liv-

ing cells without disturbing their biochemistry

Figure 8. Laser confocal microscopes produce

has been developed. Called coherent anti-Stokes

optical sections of biological specimens one plane

Raman scattering, the technique directs two

at a time.

laser beams into the cell. The frequencies of the

lasers differ by exactly the frequency at which

Laser confocal microscopy is a valuable tool

a particular chemical bond in the cell vibrates.

for obtaining high-resolution images and three-

The lasers cause the chemical bond to vibrate

dimensional reconstructions of biological speci-

and emit its own characteristic optical signal.

mens. This technique’s major value is its ability

The lasers can focus on tiny volumes and, by

to produce optical sections of a biological

29

Information about Using Technology to Study Cellular and Molecular Biology

Using Technology to Study Cellular and Molecular Biology

specimen that contain information from only

Research indicates that proteins move rapidly

one focal plane. By moving the focal plane of

throughout the nucleus in an energy-indepen-

the microscope step by step through the thick-

dent manner. Studies such as these are helping

ness of a specimen, a series of optical sections

scientists understand nuclear architecture and

can be obtained. The source of light for this

how nuclear processes are organized in the cell.

technique is a laser, because it can produce very

high intensities. The biological specimens are

While electron microscopes require that sam-

stained with a fluorescent probe to make a spe-

ples be carefully prepared and examined in

cific structure or structures visible in the pres-

a vacuum, a new family of microscopes can

ence of the laser light.

achieve electron microscope resolution in air or

even liquid, and they require much less sample

preparation. They have even been used to study

living cells. These are called scanning probe

microscopes (SPMs). These instruments use a

microscopic needle-like probe (3 to 50 nm at

the tip) that is scanned back and forth across

a surface. A three-dimensional image is con-

structed from the recorded interactions between

the probe and the atoms in the sample. The

SPM has the ability to operate on a scale from

micrometers to nanometers. It can magnify an

object up to 10,000,000 times. In the laboratory

under ideal conditions, the SPM can be used to

look at individual atoms. Furthermore, SPMs

can measure properties that other microscopes

Figure 9. Laser

cannot, such as thermal properties, friction,

confocal micro-

hardness, magnetic properties, and extent of

scope.

chemical binding.

Confocal microscopes are not large instruments.

They consist of a microscope containing a con-

focal attachment. In the example in Figure 9,

the confocal attachment is mounted on top of

the upright microscope. It contains the compli-

cated optics package. Also necessary are a large

box containing electronics, a laser, and a com-

puter for collecting and analyzing data.

Laser confocal microscopy is being used now to

study the spatial and temporal organization of

the DNA-transcription apparatus. Three-

dimensional reconstructions suggest that splic-

ing factors are stored in specific areas of the

Figure 10. Molecules of the protein GroEL

nucleus. When DNA templates are introduced,

viewed with a scanning probe microscope

these factors are recruited to sites of transcrip-

(SPM). (Reprinted here with permission from

tion in an intron-dependent fashion. The move-

Zhifeng Shao, University of Virginia. Posted

ment of proteins within the nucleus is also

at http://www.people.virginia.edu/~zs9q/zsfig/

being studied using confocal microscopy.20

random.html .)

30

Resolving the structure of biomolecules requires

visualizing individual atoms, which are only 1

to 3 Å apart when joined to form molecules.

Therefore, resolving carbon, oxygen, and nitro-

gen atoms requires a probe with a wavelength

of less than 2 Å. Light, with a wavelength of

4,000 to 7,000 Å, cannot be used for this task.

However, the wavelengths of X-rays (like elec-

trons) are short enough that the X-rays are scat-

tered by the electron clouds of molecules and

can be used to reveal the shape of a molecule.

Furthermore, X-ray techniques have some

advantages over electron microscopy for deter-

mining the structure of biomolecules, such as

proteins. For instance, the electron beam dam-

ages its target after a short exposure because it

is powerful enough to break chemical bonds.

Electron microscopy is limited to resolving bio-

molecules to no greater than about 7 Å, whereas

X-ray crystallography can be used to resolve

biomolecular structures to greater than 1 Å in

some cases.

In X-ray crystallography, X-rays, with wave-

lengths of the same order of magnitude as the

spacing between atoms, are directed through

a crystal of the substance under study (Figure

12). The X-rays are bent (or diffracted) by the

Figure 11. Myosin molecules viewed with an

electrons surrounding the atoms in the crystal.

SPM. (Reprinted here with permission from

Each diffracted X-ray is represented as a spot,

Zhifeng Shao, University of Virginia. Posted

whether recorded on film or electronically by a

at http://www.people.virginia.edu/~zs9q/zsfig/

detector.

myosin.html .)

A single molecule will not produce a detect-

able diffraction pattern, so crystals contain-

4.2 X-ray crystallography

ing many millions of identical molecules in a

X-ray crystallography of proteins is a perfect

regular pattern are used to amplify the signal.

example of the multidisciplinary approach to

After measuring the positions and intensities

technology development, since it is a combina-

of the diffraction spots, these data can be used

tion of chemistry, physics, and biology. It was

to calculate an electron density map. There are

designed to determine protein structure and, in

thousands of spots to analyze, so sophisticated

so doing, provide some information about how

computer programs and high-speed computers

proteins actually function in cells. This technol-

are needed to convert the patterns of different

ogy, like the microscopic techniques described

intensity spots into electron density maps. The

above, continues to evolve. While it provides

maps display contour lines of electron density,

detailed information about protein structure, X-

thus producing an image of the electron clouds

ray crystallography is also being used to design

of the molecule being studied. Because elec-

better medicines for treating serious diseases.

trons surround atoms more or less uniformly,

31

Information about Using Technology to Study Cellular and Molecular Biology

Using Technology to Study Cellular and Molecular Biology

Figure 12. The X-ray crystallography process.

it is possible to determine where atoms are

One of the most striking advancements has

located by looking at these maps. By rotating

been the use of synchrotron X-rays, which are

the crystal and generating an electron density

produced by the bending of particle beams gen-

map for each angle of rotation, it is possible to

erated by large accelerators. In a synchrotron,

produce a three-dimensional model of the mol-

charged particles, such as electrons or posi-

ecule. If the amino acid sequence of a protein

trons, are orbited around a path nearly a mile

is known, an accurate model of the protein can

in circumference, which must be maintained

be generated by fitting the atoms of the known

in a vacuum. Understandably, synchrotrons are

sequence into the electron density map.

quite expensive to build and to maintain, and

Figure 13 shows a typical diffraction pattern for

a single orientation of a protein crystal through

which an X-ray beam has been passed. Note

the different positions and intensities of the

spots, which mark the locations where scattered

X-rays have struck the detector. The image is

divided into quadrants because the detector was

composed of four separate, adjacent modules.

The white circle to the right of center with the

white line extending to the left is a shadow

resulting from a “beamstop.” The beamstop is a

small piece of lead mounted on a metal arm. It

prevents the intense beam of unscattered X-rays

from impinging on and damaging the detector.

Figure 14 shows a three-dimensional model of a

protein that was crystallized and then analyzed

by X-ray crystallography.

Figure 13. A typical X-ray−diffraction pattern for

a single orientation of a protein crystal through

Equipment used in X-ray crystallography con-

which an X-ray beam has been passed.

tinues to undergo development and refinement.

32

synchrotron radiation. A modern synchrotron

source can reduce total data collection to just

30 minutes, as compared with weeks using ear-

lier X-ray–diffraction equipment.

Determining structures by X-ray diffraction

continues to add to our understanding of DNA

replication and protein synthesis. For example,

scientists recently studied the crystal structures

of a bacterial DNA polymerase I that had DNA

primer templates bound to its active site.13

The enzyme was catalytically active, which

allowed for direct observation of the products

of several rounds of nucleotide incorporation.

The polymerase was able to retain its ability to

Figure 14. Three-dimensional structure of the

distinguish between correctly and incorrectly

DNA-repair protein MutY as determined by X-ray

paired nucleotides in the crystal. By comparing

crystallography. Graphic was produced from infor-

the structures of successive complexes, it was

mation available at http://www.rcsb.org/pdb/ .

possible to determine the structural basis for

sequence-independent recognition of correctly

formed base pairs.13

there are fewer than 20 in the world. Because

synchrotron X-ray beams are many orders of

Ribosomes are the largest asymmetric structures

magnitude brighter than the usual laboratory X-

to be solved by X-ray crystallography so far.

ray sources, data for single crystal orientations

Results, with resolutions as high as 2.4 Å, have

can be collected with exposures of a minute or

helped establish the locations of the 27 proteins

less, rather than exposures of several minutes to

and the 2,833 bases of ribosomal (rRNA) found

an hour.

within the ribosome.4 The structure also shows

that contacts between the two ribosome sub-

The completion of the Human Genome Proj-

units are limited, which helps explain why the

ect has provided the foundation for explosive

ribosome subunits dissociate so readily.

growth in structural biology. Technological

advances in X-ray crystallography have greatly

Some biomolecules or biomolecular complexes

reduced the time and effort required to solve

are not suitable for diffraction analysis because

structures. In addition to synchrotron X-

they cannot be crystallized. Scientists, however,

rays, advances include faster X-ray detectors,

are optimistic about developing techniques to

improved computational methods for process-

deal effectively with noncrystalline materials.18

ing data, and robotics for growing and handling

This will make it possible to image everything

crystals. Structure determinations that used to

from cells to individual protein molecules.

involve a 20-person, yearlong effort now con-

stitute a single chapter in a graduate student’s

4.3 Nuclear magnetic resonance (NMR)

thesis. The Protein Structure Initiative, remi-

spectroscopy

niscent of the Human Genome Project, aims to

Most people know of magnetic resonance imag-

produce the three-dimensional structures for

ing (MRI) as an important diagnostic tool in

the estimated 1,000 to 5,000 distinct spatial

medicine that can produce incredible images

arrangements assumed by polypeptides found

of soft tissues. Less well known is that MRI

in nature. Such high-throughput data collection

represents only a limited area of NMR. NMR

is best suited to X-ray crystallography using

depends on the fact that atomic nuclei having

33

Information about Using Technology to Study Cellular and Molecular Biology

Using Technology to Study Cellular and Molecular Biology

an odd number of protons, neutrons, or both

in plants. This enzyme functions as a molecular

have an intrinsic spin. When such a nucleus is

motor that uses an internal rotary mechanism.

placed in a magnetic field, it can align either in

NMR has been used to reveal structural changes

the same direction as the field or in the oppo-

in a protein subunit of the enzyme that may

site direction. A nucleus aligned with the field

explain how the rotation is driven.20

has a lower energy than one aligned against it.

NMR spectroscopy refers to the absorption of

Many see the successful Human Genome Project

radiofrequency radiation by nuclei in a strong

as providing a foundation for a major initiative

magnetic field. Absorption of energy causes the

in structural biology in which NMR will play

nuclei to realign in the higher-energy direction.

a critical role.5 Informal groups of scientists in

The nuclei then emit radiation and return to

the United States are proposing the creation of

the lower-energy state. The local environment

10 regional “collaboratories,” each with power-

around each nucleus will distort the magnetic

ful new-generation NMR spectrophotometers

field slightly and affect its transition energy.

to assist with high-throughput structure deter-

This relationship between transition energy and

minations. Universities, too, are interested in

an atom’s position within a molecule allows

establishing collaborative centers in genomics

NMR to provide structural information.

and proteomics.9 At Stanford, Nobel Prize–

winning physicist Steven Chu and biochemist

One advantage of NMR spectroscopy over X-ray

James Spudich are leading an effort to create

crystallography and electron microscopy is that

an interdisciplinary research center housing 50

it can be applied to the study of movement at

faculty members, while Princeton University is

the molecular level. NMR studies are providing

planning to add an interdisciplinary genomics

a growing list of cases where conformational

institute to its molecular biology department.

dynamics correlate with protein-protein interac-

tion on surfaces. For example, the enzyme ATP

4.4 Laser technology

synthase catalyzes the formation of ATP from

When the laser made its first appearance in

ADP and phosphate during oxidative phosphor-

the 1950s, it was a tool without a task. Since

ylation in animals and photophosphorylation

then, the laser has been put to myriad uses in

our everyday lives—from scanning prices at the

supermarket to playing music and printing text.

Similarly, in scientific research, the laser has

found many applications. It is like a Swiss Army

knife, having many blades with a variety of uses.

Combining lasers and microscopy has greatly

expanded our ability to image cellular and

molecular structures. Cells, or parts of cells,

can be exposed to antibodies or nucleic acid

probes labeled with fluorescent dyes. When

excited by laser light of the appropriate wave-

length, specific areas of the cell, or regions of

a chromosome, can be visualized. The resolu-

tion of optical microscopy is limited by physical

laws. Diffraction prevents the laser beam (and

therefore the spot of fluorescence) from being

focused any finer than about 200 nm. However,

a new approach is overcoming this limit. It uses

Figure 15. Equipment for high-resolution nuclear

a combination of two laser beams, one to illu-

magnetic resonance (NMR) spectroscopy.

minate and image the sample, and a second that

34

shapes the first beam and reduces the effects of

diffraction. The technique has been used to dis-

The amount of genetic data available

tinguish crystals only 100 nm apart and is still

and the rate of acquisition are astonish-

undergoing improvement.

ing by any measure.

Lasers, together with magnets, are being used

to develop technologies for manipulating single

The use of computers to model protein folding

molecules. Investigators are now able to exam-

is one of the primary efforts in the postsequenc-

ine how DNA interacts with the various protein

ing phase of the Human Genome Project. In the

molecules that cut, paste, and copy it. DNA is

1970s, when the first proteins were modeled,

an ideal choice for single-molecule studies. It

the structures generated were in vacuo (in a vac-

is a very large molecule (the longest human

uum), with no other molecules interacting with

chromosome stretches to 9 centimeters) and

the protein. Of course, each protein in a living

quite robust. For example, scientists have suc-

cell is surrounded by thousands of water mol-

ceeded in using lasers as optical tweezers to tie

ecules, and these have an important effect on

knots in single DNA molecules.2 Results indi-

the protein’s conformation. Indeed, research has

cate that knotted DNA is stronger than actin, a

demonstrated that the water-containing models

major muscle protein. Although tying DNA into

of proteins are much better predictors of how

knots may not seem particularly useful, it does

the proteins look and function within a cell.10

provide insight into the molecule’s mechanical

properties, which are critical to understanding

The importance of protein folding was recently

how enzymes interact with it.

recognized by IBM, which announced that it

would spend $100 million to build a supercom-

4.5 Simulations and computations

puter called Blue Gene. The five-year IBM initia-

The explosion of data produced by the Human

tive will involve modeling how proteins take on

Genome Project led to the creation of a new

their three-dimensional shapes. A major aim is

discipline, bioinformatics, whose focus is on

to help drug researchers identify drug targets for

the acquisition, storage, analysis, modeling, and

treating diseases. Protein folding is a daunting

distribution of the many types of information

problem. Even Blue Gene, which will be 500

embedded in DNA and protein-sequence data.14

times faster than the current fastest computer,

Biologists are familiar with the terms in vivo and

will require about one year to simulate the com-

in vitro, used to describe processes that occur

plete folding of a typical protein. The stakes,

in the body and in the test tube, respectively.

however, are huge. Approximately one-third

Now they are becoming acquainted with a new

of the genes identified in the newly sequenced

term, in silico, used to describe a new branch

human genome are of unknown function and

of biology that requires little more than a com-

are therefore of particular academic and com-

puter and a connection to the Internet. As more

mercial interest. New companies are formed

and more DNA and protein sequence data find

on a monthly basis to take part in this genetics

their way into computer databases, the ability

sweepstakes.

of bioinformatics to address biological ques-

tions becomes more powerful. The amount of

5 Technology and the Origins of

genetic data available and the rate of acquisition

Molecular Biology

are astonishing by any measure. According to

This section provides a brief history of the ori-

Francis Collins, head of the National Human

gins of molecular biology. It addresses the gene’s

Genome Research Institute, it took four years

chemical nature, organization, and behavior.

to obtain the first 1 billion base pairs of human

Despite molecular biology’s narrow focus on

sequence and just four months to get the second

DNA, it is readily apparent that many of the

billion.16

most important advances in the field have relied

35

Information about Using Technology to Study Cellular and Molecular Biology Using Technology to Study Cellular and Molecular Biology

heavily on technology-based contributions from

unaware of the important one-gene–one-enzyme

chemistry and physics. This is addressed in the

work of George Beadle and Edward Tatum from

National Science Education Standards. The His-

the early 1940s), the book has been credited

tory and Nature of Science Content Standard

with influencing a generation of physicists to

G states, “As a result of activities in grades 9 to

consider biological questions.

12, all students should develop understanding

of . . . historical perspectives.” It further states,

Soon, the ranks of the Phage Group began to

“Occasionally, there are advances in science and

grow. It included other physicists, such as Leo

technology that have important and long-lasting

Szilard, holder of the patent for the nuclear

effects on science and society.”

chain reaction and a participant in the Man-

hattan Project, and Thomas Anderson, one

Science historians often attribute the origins of

of the first American electron microscopists.

molecular biology to the Phage Group, which

Micrographs obtained by Anderson and Roger

first met in 1940 at Cold Spring Harbor Labora-

Herriott showed that phage begin the infection

tory in Long Island, N.Y. At the center of the

process by attaching to bacteria by their tails.

group were three scientists. Max Delbrück, a

Later, empty phage “ghosts” could be seen on

German physicist working at Vanderbilt Uni-

the bacterial surface.

versity, and Salvador Luria, an Italian biologist

working at Indiana University, had fled to the

Hershey and his colleague Martha Chase used

United States from Nazi Europe. They were

phage to examine the molecular nature of the

joined at Cold Spring Harbor by Alfred Hershey,

gene.11 They took advantage of radioactive iso-

an American biologist working for the Carnegie

topes that became available as a consequence

Institution’s Department of Genetics.

of work on the atomic bomb. Despite the ear-

lier work of Oswald Avery and his colleagues

Bacteriophage, also called phage, are viruses

demonstrating that DNA was the hereditary

that infect bacteria.1 These were discovered in

substance,3 many scientists continued to believe

1916 by the English microbiologist F.W. Twort

that genes could only be made of protein. Her-

and, independently, two years later by the

shey and Chase began their experiment by

French-Canadian F. d’Herelle. It was d’Herelle

using radioactive phosphorous to label phage

who came up with the name bacteriophage.

DNA and radioactive sulfur to label phage pro-

Phage became an important area of research in

tein. They tried to detect which radiolabel went

the 1920s, when scientists hoped they could be

inside the bacterium to direct synthesis of new

used to treat bacterial diseases. When this hope

phage particles after the bacterium was infected.

failed to materialize, phage research fell out of

At first, they could not effectively detach the

favor until the Phage Group resurrected it.22

phage particles from the surfaces of the bacte-

rial cells, but then an unexpected technology

In 1944, Delbrück organized a summer course

came to their aid. They used a Waring blender,

at Cold Spring Harbor Laboratory to introduce

originally designed to mix cocktails, to disrupt

other scientists to the quantitative methods for

the attachments of the phage to the bacterial

studying phage that he and Luria had devel-

cells. The radioactive phosphorous went into

oped. In that same year, the great Austrian

the bacterial cells, while the radioactive sulfur

physicist Erwin Schrödinger published a book

remained outside with the phage ghosts, con-

titled What Is Life? that discussed heredity from

firming that DNA, and not protein, contains the

a physics perspective.19 Schrödinger reasoned

genetic information. This work set the stage for

that although living things obey the laws of

the contribution of the youngest member of the

physics, they also might be governed by undis-

Phage Group, James Watson.

covered physical laws. Although biologists of

that time regarded Schrödinger’s book as roman-

Watson came to the Cavendish Laboratory at

tic and a bit naive (for example, he seemed

Cambridge University in 1951, ostensibly to

36

study the three-dimensional structures of pro-

Samples of cells were removed before the switch

teins. He quickly fell in with Francis Crick, a

to the light-isotope growth medium (genera-

British physicist, who had developed an inter-

tion 1) and from the first two generations fol-

est in heredity after reading Schrödinger’s What

lowing the switch (generations 2 and 3). DNA

Is Life? The pair formed a collaboration that

samples extracted from the cell samples were

resulted two years later in the proposal of the

centrifuged through a solution of cesium chlo-

double helix model of DNA.23 Although Watson

ride that forms a density gradient during cen-

and Crick relied on model building to solve

trifugation (for 20 hours at 40,000 revolutions

DNA’s structure, they could not have succeeded

per minute). DNA molecules form a discrete

without help from two other scientists at Cam-

band at a position where their density equals

bridge, Maurice Wilkins and Rosalind Franklin.

that of the cesium chloride gradient. The DNA

Wilkins first, and then Franklin, used X-ray

samples taken from generation 1 contained a

diffraction to study the structure of DNA. In

single heavy band, since both DNA strands con-

the case of DNA fibers, the diffraction patterns

tained the 15N isotope. Samples from generation

suggested that the molecule was some type of a

2 displayed a single band of medium density,

helix with a diameter of 20 Å and a repeat of 34

since each DNA molecule consisted of one

Å. Near the end of the paper that describes the

heavy (15N) parental strand and one light (14N)

double helix, Watson and Crick included the

complementary strand. Finally, samples from

statement, “It has not escaped our notice that

generation 3 displayed bands of two different

the specific pairing we have postulated immedi-

densities. One band of medium density again

ately suggests a possible copying mechanism for

consisted of a heavy parental strand and a new

the genetic material.”

complementary light strand. A second band of

light density consisted of two strands of light

Experimental support for a copying mechanism

DNA, one an inherited light parental strand and

suggested by the double helix structure came in

the other, a new complementary light strand.

1958 from Matthew Meselson and Frank Stahl,

then working at the California Institute of Tech-

Around the time that Meselson and Stahl were

nology. In what some have called “the most

performing their experiments, Crick theorized

elegant experiment in molecular biology,” they

that genetic information flow resided in DNA,

demonstrated that DNA replicates in a semicon-

passed through an RNA intermediate, and

servative fashion, during which one parental

became expressed as a sequence of amino acids.

DNA strand serves as the template for the syn-

Using the electron microscope, it was possible

thesis of a new complementary strand.17 Their

to visualize DNA and RNA molecules that first

ingenious approach involved using a heavy

had been stained with heavy metals. Using

isotope of nitrogen and the ability of density

extracts from bacteria, scientists were able

gradient centrifugation to distinguish this heavy

to glimpse Crick’s “central dogma” in action.

form (15N) from the normal light form (14N).

Micrographs were obtained that showed newly

synthesized RNA molecules branching off from

Meselson and Stahl grew Escherichia coli in

a transcribed region of DNA. Furthermore,

a nutrient medium containing only 15N as a

ribosomes could be seen already attaching to

source of nitrogen. DNA replication introduced

the growing RNA chains. Not only did electron

the heavy isotope of nitrogen into the bacterial

microscopy provide this comprehensive view of

DNA. After 14 generations, the bacteria were

gene expression, it also was about to produce

placed into a medium that contained only 14N

critical insight into gene organization.

as a nitrogen source. During the subsequent

replication, the light isotope was incorporated

In 1977, the laboratories of Phillip Sharp

into the bacterial DNA.

and Richard Roberts independently used the

electron microscope to make a fundamental

37

Information about Using Technology to Study Cellular Teacher

and

Background

Molecular Biology

Information

Using T

about Energy

echnology to

Balance

Study Cellular and Molecular Biology

discovery about gene organization and expres-

to a manipulative one. In a similar way, the rise

sion. First in adenovirus, and later in eukary-

of structural biology is helping propel biology

otic DNA, it was shown that some genes are

toward another paradigm shift. Currently, over

interrupted by stretches of DNA that are not

500,000 human DNA sequences are contained

represented in the messenger RNA (mRNA).

in genetic databases. It is estimated that these

For example, DNA containing the gene for

may give rise to 160,000 targets for drug devel-

ovalbumin was denatured and hybridized to

opment.

ovalbumin mRNA. Electron micrographs of the

hybrid revealed regions of heteroduplex forma-

6 The Goal of This Supplement

tion alternating with a series of seven loops that

The goal of this curriculum supplement is to

corresponded to regions of genomic DNA that

help prepare high school biology students for

have complementary sequences in the mRNA.

the technological world they will inherit. This

The regions of a gene found in the mRNA are

is consistent with the National Science Education

called exons, because they are expressed in the

Standards. For example, Science and Technol-

gene product. Regions not found in the mRNA

ogy Content Standard E states, “As a result of

are called introns, because they are located in

activities in grades 9 to 12, all students should

between the exons.

develop . . . understandings about science and

technology.” A fundamental concept that under-

The origins and early development of molecular

lies this standard is that science advances with

biology would not have been possible without

the introduction of new technologies, and solv-

biophysical techniques such as X-ray diffrac-

ing technological problems results in new scien-

tion, electron microscopy, and isotope labeling.

tific knowledge. New technologies also extend

These techniques, along with others, continue

scientific understandings and introduce new

to be refined and extended to new areas of biol-

areas of research.

ogy. As biology becomes more data intensive, it

relies increasingly on biophysical techniques.

The technologies presented in this supplement

are new to most high school students. Very few

The completion of the Human Genome Project

students will have had much exposure to chem-

marks the end of the effort to decode the entire

istry or physics, and students in your classes

set of human genes. It also marks the unof-

will be spending only about a week with this

ficial start of the next phase of our continuing

supplement. A detailed understanding of each

quest to understand how genetics contrib-

technique should not be the primary objective of

utes to human health and well-being. Biology

the supplement. Rather, students should come

underwent a paradigm shift more than 30 years

away from it with an appreciation of some of the

ago after the discovery of restriction enzymes.

applications and implications of technology in

These enzymes are just tools, yet they helped

the study of cellular and molecular biology.

shift biology from a largely descriptive science

38

Glossary

angstrom: Unit of measurement defined as

probe: An exploratory device, especially one

1 × 10–10 meter and represented by the symbol

designed to investigate and obtain information

Å; a sheet of paper is about 1,000,000 Å thick.

about an unknown region or object.

bacteriophage: Viruses that infect bacteria.

radiofrequency radiation: Electromagnetic

waves with a wavelength of 1 millimeter to

bioinformatics: The study of the inherent struc-

30 meters.

ture of biological information and biological

systems. It brings together biological data from

rational drug design: See target-based drug

design.

genome research with the theory and tools of

mathematics and computer science.

resolution: A measure of the ability of a system

to form separate and distinct images of two

infectious agent: A living organism that enters

objects of a given angular separation.

and multiplies in a host (that is, produces an

infection); the infection can be without symp-

scale: A series of ascending and descending

toms, or it can produce disease.

steps to assess the relative or absolute size of

some property of an object. Scales can be linear

laser: A device that produces a narrow, power-

or logarithmic.

ful beam of light.

spectroscopy: The study of the distribution of

magnetic field: A region in space created by

a characteristic of a system or phenomenon,

moving electrons (that is, an electric current);

especially the distribution of energy emitted by

this produces a force that causes other electrons

a system or the distribution of atomic or sub-

to move, thus creating another electric current.

atomic particles in a system.

micrograph: A graphic reproduction of the

striated muscle: Muscle tissue, such as skel-

image of an object formed by a microscope.

etal muscle, that is made up of long fibers and

is characterized by alternating light and dark

nanometer: Unit of measurement defined as

bands.

1 × 10–9 meter and represented by the abbrevia-

tion nm.

synchrotron: A name given to X-rays or light

produced by electrons circulating at nearly the

pathogen: An agent, such as bacteria, viruses,

speed of light. These can be used to investigate

and fungi, that produces disease.

atomic and molecular structure.

pathology: The study of disease or any condi-

target-based drug design: Also called rational

tion that affects the length or quality of life.

drug design, an approach based on the

39

Using Technology to Study Cellular and Molecular Biology

development of molecules (potential drugs) to

X-ray: Electromagnetic energy having a wave-

interact specifically with a biological structure

length in the approximate range from 0.01 to

involved in disease. The biological structure

10 nanometers.

may be a pathogen, a product of the pathogen

(such as a protein), or a molecule (such as a

X-ray diffraction: The scattering of X-rays by

protein or other disease-causing molecule) of

crystal atoms that produces a pattern that yields

a host cell that interacts with a pathogen or a

information about the structure of the crystal.

pathogen product.

The wavelengths of X-rays are comparable in

size to the distances between atoms in most

technology: A body of knowledge used to cre-

crystals. X-ray diffraction is the basis of X-ray

ate tools, develop skills, and extract or collect

crystallography.

materials; the application of science (the combi-

nation of the scientific method and material) to

meet an objective or solve a problem.

wavelength: The distance between one peak of

a wave of light, heat, or other energy and the

next corresponding peak.

40

References

1.

Anderson, T.F. 1966. Electron microscopy

7.

Clemons, W.M., May, J.L.C., Wimberly,

of phage. In J. Cairns, G.S. Stent, and

B.T., McCutcheon, J.P., Capel, M.S., and

J.D. Watson, eds. Phage and the Origins

Ramakrishnan, V. 1999. Structure of a

of Molecular Biology (pp. 63−78), Long

bacterial 30S ribosomal subunit at 5.5 Å

Island, N.Y.: Cold Spring Harbor Labora-

resolution. Nature, 400: 833−840.

tory Press.

8.

Gabashvili, I.S., Agrawal, R.K., Spahn,

2.

Arai, Y.,Yasuda, R., Akashi, K., Harada,

C.M., Grassucci, R.A., Svergun, D.I.,

Y., Miyata, H., Kinosits, K., and Itoh, H.

Frank, J., and Penczek, P. 2000. Solution

1999. Tying a molecular knot with optical

structure of the E. coli 70 S ribosome at

tweezers. Nature, 399: 446−448.

11.5 Å resolution. Cell, 100(5): 537−549.

3.

Avery, O.T., MacLeod, C.M., McCarty,

9.

Garwin, L. 1999. U.S. universities cre-

M. 1944. Studies on the chemical nature

ate bridges between physics and biology.

of the substance inducing transforma-

Nature, 397: 3.

tion of pneumococcal types. Induction

of transformation by a desoxyribonucleic

10. Gerstein, M., and Levitt, M. 1998. Mol-

acid faction isolated from pneumococcus

ecules of life. Scientific American, 279(5):

type III. Journal of Experimental Medicine,

101−105.

79(2): 137−168.

11. Hershey, A.D., and Chase, M. 1952. Inde-

4.

Ban, N., Nissen, P., Hansen, J., Moore,

pendent functions of viral protein and

P.B., and Steitz, T.A. 2000. The complete

nucleic acid in growth of bacteriophage.

atomic structure of the large ribosomal

Journal of General Physiology, 36: 39−56.

subunit at 2.4 Å resolution. Science, 289:

878−879.

12. International Technology Education Asso-

ciation (ITEA). 2000. Standards for Tech-

5.

Burley, S.K., Almo, S.C., Bonnano, J.B.,

nological Literacy: Content for the Study of

Capel, M., Chance, M.R., Gaasterland,

Technology. Reston, Va.: ITEA.

T., Lin, D., Sali, A., Studier, F.W., and

Swaminathan, S. 1999. Structural genom-

13. Kieffer, J.R., Mao, C., Braman, J.C., and

ics: beyond the human genome project.

Beese, L.S. 1998. Visualizing DNA replica-

Nature Genetics, 23: 161−167.

tion in a catalytically active Bacillus DNA

polymerase crystal. Nature, 391: 304−307.

6.

Cate, J.H., Yusupov, M.M., Yusupova,

G. Zh., Earnest, T.N., and Noller, H.F.

14. Liszewski, K. 2000. Bioinformatics leads

1999. X-ray crystal structures of 70S ribo-

analysis of genomic data. Genetic Engi-

some functional complexes. Science, 285:

neering News, 20(1): 3.

2095−2104.

41

References

Using Technology to Study Cellular and Molecular Biology

15. Loucks-Horsley, S., Hewson, P., Love, N.,

20. Rastogi, V.K., and Girvin, M.E. 1999.

and Stiles, K. 1998. Designing Professional

Structural changes linked to proton trans-

Development for Teachers of Science and

location by subunit c of the ATP synthase.

Mathematics. Thousand Oaks, Calif.: Cor-

Nature, 402: 263−268.

win Press.

21. Schrödinger, E. 1944. What Is Life: With

16. Marshall, E., Pennisi, E., and Roberts,

Mind and Matter and Autobiographical

L. 2000. In the crossfire: Collins on

Sketches. Cambridge, UK: Cambridge Uni-

genomes, patents, and “rivalry.” Science,

versity Press.

287: 2396−2398.

22. Stent, G.S. 1966. Introduction: Waiting

17. Meselsohn, M., and Stahl, F. 1958. The

for the paradox. In J. Cairns, G.S. Stent,

replication of DNA in Escherichia coli.

and J.D. Watson, eds. Phage and the Ori-

Proceedings of the National Academy of Sci-

gins of Molecular Biology (pp. 3−8). Long

ences USA, 44: 671−682.

Island, N.Y.: Cold Spring Harbor Labora-

tory Press.

18. Miao, J., Charalambous, P., Kirz, J., and

Sayre, D. 1999. Extending the method-

23. Watson, J.D., and Crick, F.H.C. 1953.

ology of X-ray crystallography to allow

Molecular structure of nucleic acids: a

imaging of micrometre-sized noncrystal-

structure for deoxyribose nucleic acid.

line specimens. Nature, 400: 342−344.

Nature, 171: 737−738.

19. Phair, R.D., and Misteli, T. 2000. High

mobility of proteins in the mammalian

nucleus. Nature, 404: 604−609.

42

4

Lesson 1

Engage

Explore

What Is Technology?

Explain

Overview

At a Glance

This lesson consists of two activities linked by classroom discussion. Its

purpose is to engage students in the general topic of technology. The first

activity involves classroom discussion and a short scenario to allow stu-

dents to develop a sense of what technology is and to dispel the notion

that technology relates mostly to computers. The second activity intro-

duces students to the concept of scale by using the classroom to repre-

sent a cell and other smaller objects to represent subcellular components.

Major Concepts

Technology is a body of knowledge used to create tools, develop skills,

and extract or collect materials. It is also the application of science (the

combination of the scientific method and material) to meet an objective

or solve a problem. Scale is a way to represent the relationship between

the actual size of an object and how that size is characterized, either

numerically or visually.

Objectives

After completing this lesson, students will

• be able to explain what technology is,

• recognize that human intervention is the common bond among tech-

nologies, and

• describe the use of scale to distinguish between objects of different size.

Teacher Background

See the following sections in Information about Using Technology to

Study Cellular and Molecular Biology:

1 Introduction (page 23)

2 Major Preconceptions (pages 23–24)

3.1 Scale (pages 24–25)

43

Using Technology to Study Cellular and Molecular Biology

In Advance

Web-Based Activities

Activity

Web Version

1

No

2

No

Photocopies

Activity 1

none

Activity 2

Master 1.1, Searching for Scale, 1 copy per student

Materials

Activity 1

none needed

• meter stick

Activity 2

• rulers

• objects of various sizes (see Teacher note on page 49)

Preparation

Activity 1

No preparations needed.

Activity 2

No preparations needed.

Activity 1: Technology—What’s It All About?

Procedure

Tip from the field test: Activities 1 and 2 can be conducted in several

ways. You can engage the class as a whole in discussion as directed.

Alternatively, you can divide the class into groups of three to five stu-

dents each, ask each group to consider the questions you ask, and then

have each group provide its responses. It is also possible to have stu-

Assessment:

dent groups consider only a limited number of the questions and then

This activity is

handle the remainder with the whole class. If you choose either of the

designed to engage

last two approaches, you should limit the time allotted for groups to

students in learning

consider each question to several minutes. Field-testing indicated that no

about technology and

approach was superior to another.

to help the teacher

assess the students’

1.

Begin by asking the class, “How do you define technology?”

prior knowledge of the

subject.

Accept all answers and write student responses on the board. Do

not attempt to have students refine their definitions of technology

at this point. They will revisit their definitions and refine them in

44

Step 5. Students, like older individuals, may harbor the precon-

ception that technology relates mostly to computers. Through

advertisements and media articles, they are familiar with the terms

information technology and computer technology.

Teacher note: Asking this question requires students to call on

their prior knowledge, and it engages their thinking. At this point,

do not critique student responses. Appropriate teacher comments

are short and positive, such as “good” and “what else?” Other

appropriate teacher responses include, “Why do you believe that?”

or “How do you know that?” Questions such as these allow the

teacher to assess students’ current knowledge about the subject and

to adjust lessons accordingly. They also provide a springboard to

“Let’s find out” or “Let’s investigate.” In general, it is time to move

forward when the teacher sees that thinking has been engaged.

2.

Ask students, “In general, what does technology do for us?”

This question may help students understand that technology helps

us solve problems, makes our lives easier, and extends our abilities

to do things. Technology is used to develop skills or tools, both in

our daily lives and in our occupations.

3.

Focus discussion on technologies that are relevant to each stu-

dent’s life. Ask students to look around the room. What technolo-

gies do they see? How do these technologies solve problems and

make their lives easier?

Accept all responses and write them on the board. Students may

mention any number of items. Some may be school-related, such

as binders, backpacks, pens, pencils, paper, and paper clips. Other

items may be more personal, such as water bottles, personal ste-

reos, and hair clips. Students may neglect items such as shoelaces,

zippers, buttons, fabric, eyeglasses or contact lenses, makeup, and

bandages. Discussion should reinforce the notion that humans

develop technology with a specific objective in mind. A related

concept is that a given task requires the right tool or tools.

4.

Pick a technology that students have mentioned. Ask them what

types of knowledge were required to develop that technology.

Students may not realize that technologies are generally developed

by applying knowledge from multiple disciplines. For example,

producing today’s audio devices, such as a portable CD player,

requires knowledge obtained from engineering, physics, mathemat-

ics, chemistry, and computer science.

5.

On the basis of previous discussions, ask students to rethink and

refine their definition of technology (from Step 1).

45

Student Lesson 1

Using Technology to Study Cellular and Molecular Biology

Students should mention that technology is a way of solving prob-

lems through the application of knowledge from multiple disci-

plines.

6.

Tell students to imagine that they live in the Stone Age. Their

only garment has been ripped and requires mending. How would

they do it?

Students first should recognize that the ripped garment is a prob-

lem requiring a solution. They should consider what technologies

they have available. The Stone Age was a period early in the devel-

opment of human cultures when tools were made of stone and

bone. Clothing consisted of animal skins or fabrics woven from

threads derived from plant fibers. Bones and sharp reeds were used

to make needles.

7.

Ask students how their approach to mending the garment would

change as time advanced from the Stone Age to the present. What

new knowledge would allow the development of new technology?

Student responses will vary, and some students may want to jump

Content Standard E:

directly from the Stone Age to the modern sewing machine. Slow

Technological design

them down and have them consider incremental changes in knowl-

is driven by the need

edge and technologies. They may cite the use of metals to fashion

to meet human needs

repair tools, like knives and finer needles. New knowledge of met-

and solve human

als and chemistry would help here. Later advances in engineer-

problems.

ing and mechanics would lead to the development of human-run

machines for assisting with repairs. Eventually, advances in physics

(electricity) and engineering led to the invention of modern sewing

machines. Similarly, advances in agriculture, chemistry, and engi-

neering produced better fabrics and threads. Students should derive

an understanding that technology advances through interactions

among multiple disciplines. While a problem may remain basically

the same over time (for instance, the need to make or repair cloth-

ing), advances in technology change how the problem is solved.

8.

Write the words problem and technology on the board. Ask students to use arrows to draw a graphic that represents the

relationship they believe exists between a problem and the tech-

nology to solve it.

Assessment:

Listening to students’

They can use arrows of any kind, and they should be prepared to

responses wil help you

defend their suggestions. The graphic should illustrate that a

assess their understand-

ing of the relationship

between problems and

technology.

46

problem does not drive technology unidirectionally, nor does tech-

nology exist solely in search of a problem to solve. Rather, these

two areas exist to support and drive one another. Solving problems

does require the development of new technologies, which can then

be applied to other problems. A graphic to depict this indicates the

cyclic relationship between the two:

Activity 2: Searching for Scale

1.

Biological molecules are small, but how small is “small”? Ask students these two questions:

a.

How do biological structures, such as cells, organelles, bac-

teria, and viruses, compare in size with one another?

b.

How do molecules compare in size with biological struc-

tures such as cells, organelles, bacteria, and viruses?

Accept all responses and write them on the board. Students will

explore these size relationships in the next steps.

2.

Tell students that they will now investigate the relative sizes of

different biological structures and see how close their estimates

of relative size were.

3.

Give each student a copy of Master 1.1, Searching for Scale. Work with the class to complete column 3, Size relative to cell.

The table with column 3 completed is as follows:

47

Student Lesson 1

Using Technology to Study Cellular and Molecular Biology

Biological

Actual

Size

Object

Mea-

Size

Structure Diameter Relative to Cell

Used to

sured

Relative

(in

Model

Size of to Model

Meters)

Biological Model Cell (the

Structure

Object

Room)

Cell

1 × 10–5

1 × 10–5

Room

10 m

10

= 1

= 1

1 × 10–5

10

Bacterium 1 × 10–6

1 × 10–6

Desk

1 m

= 1

1 = 1

1 × 10–5

10

10 10

Mitochon- 5 × 10–7

5 × 10–7

0.5 m

= 1

drion

1 × 10–5

20

Virus

1 × 10–7

1 × 10–7

0.1 m

= 1

1 × 10–5 100

(10 cm)

Ribosome 1 × 10–8

1 × 10–8

0.01 m

= 1

1 × 10–5 1,000

(1 cm)

Protein

5 × 10–9

5 × 10–9

0.5 cm

= 1

1 × 10–5 2,000

Glucose

1 × 10–9

1 × 10–9

0.1 cm

=

1

molecule

1 × 10–5 10,000

(1 mm)

H2O

1 × 10–10 1 × 10–10

0.1 mm

=

1

molecule

1 × 10–5 100,000

4.

Tell students that the information in columns 2 and 3 each can

be used to construct scales to describe the sizes of the different biological structures in the table. Ask students to define scale.

Accept all answers and write them on the board. Guide discussion

Content Standard A:

so that students realize that scale is a way to represent the relation-

Mathematics is essen-

ship between the actual size of an object (for example, its length or

tial in all aspects of

mass) and how that size is characterized either numerically or visu-

scientific inquiry.

ally. A scale is a series of ascending and descending steps to assess

either some relative (column 3) or absolute (column 2) property of

an object. In this case, the property being investigated is size.

5.

Ask students to try to visualize the 100,000-fold difference in

size between a cell and a water molecule. Can they do it? How

could they demonstrate this large size difference more easily?

Master 1.1, Searching for Scale provides the necessary clues for stu-

dents, since the heading of column 4 is Object used to model biologi-

cal structure. Students can use larger structures, such as a room, to

model smaller ones, such as a cell, to make size differences more

apparent and bring them into the realm of common experience.

6.

Ask two students to use a meter stick to mark approximately

10 m along both the length and width of the classroom.

48

It is okay if the classroom does not allow 10 m to be measured in

either or both directions. A distance of 7 to 9 m will still make the

point visually. However, for ease of calculations to follow, use room

dimensions of 10 m even if the actual dimensions are smaller than

that.

7.

Tell students that the space defined by 10 m wide, 10 m in

length, and the height of the room now represents a cell. In other

words, this space is now a model for a typical cell.

8.

Organize students into pairs and give each pair a ruler.

9.

Tell students that they will be searching the classroom for

objects that model the biological structures on Master 1.1,

Content Standard A:

Searching for Scale.

Recognize and analyze

alternative explana-

Explain that they will be looking for objects that have the same

tions and models.

size relative to the model cell (the room) that the actual biological

structure has to a real cell.

10. Ask students to look at the last three columns on Master 1.1,

Searching for Scale. As an example, a desk measuring 1 meter

high is provided as a model for a bacterium. Important points are

as follows:

Assessment:

Circulate around the

1

a.

A bacterium is the size of an actual cell (column 3).

room, noting whether

10

students understand

1

b.

Similarly, the desk is

10 the size of the model cell, the

the mathematics

room (1 m compared with 10 m; columns 4 and 5).

involved in scaling

objects for this activity.

c.

Because it is of the correct scale, the desk can be used to

model a bacterium if a cell is modeled by a room 10 m

across.

11. Instruct student pairs to locate items in the classroom that can

be used to model the biological structures listed on Master 1.1,

Searching for Scale. They should enter their results in columns 4, Assessment:

5, and 6 of the master. Allow 15 minutes for this activity.

Listening to student

responses will help

Students may approach this activity in different ways. Some may

you assess their under-

find it useful to determine the size of the object they are looking

standing of scale and

for first by multiplying the ratio in column 3 by 10 m. Some stu-

modeling. Collecting

dents may begin by locating objects, measuring them, and then

their completed tables

determining whether they meet the size requirements.

(Master 1.1, Search-

ing for Scale) allows

Teacher note: It is helpful to have objects available in the class-

a more formal oppor-

room that will meet the size requirements for modeling the bio-

tunity to evaluate stu-

logical structures in Master 1.1. Objects, such as erasers, marbles,

dents’ understanding.

49

Student Lesson 1

Using Technology to Study Cellular and Molecular Biology

fine- and ultrafine-tip pencils or pens, pieces of candy, an inflated

balloon, balls of different sizes, and other easily obtained materi-

als, ensure that students will be able to find something to serve as a

model for each structure.

12. Ask student pairs to share some of their results with the class.

Students should realize that the size ratios in columns 3 and 6 are

the same. In other words, modeling allows relative sizes to be stud-

ied, although the actual sizes of the real biological structure and its

model differ quite a bit.

Discussion Questions

1.

If a cell of 1 × 10–5 m (10 × 10–6 m, or 10 µm) diameter is repre-

sented by a room 10 m across, what distance would represent a

human 2 m tall?

First, as in column 3 of Master 1.1, Searching for Scale, derive the

relationship between the size of the human and the size of the cell:

2 meters ÷ (1 × 10–5 meter) = 2 × 105.

Thus, a 2-m-tall individual is 2 × 105 times larger than a cell

1 × 10–5 m in diameter.

If the cell is represented by a distance of 10 m, the 2-m-tall indi-

vidual would be represented by a distance of

10 m × (2 × 105) = 2 × 106 m (2,000 km, or 1,250 miles)

As a reference, this distance is the same as that from Boston to

Miami, Kansas City to Boston, or Los Angeles to Dallas. This cal-

culation is intended to provide a “wow” for the students, and they

derive an understanding of the difference in size between a human

and a molecule (in this example, the difference between

2,000,000 m for the human and 2 to 5 mm for a protein). This

should help students understand the need for specialized technolo-

gies for studying living systems at the cellular and molecular levels.

2.

As a lead-in to Lesson 2, write the following terms on the board

in random order: Eye; Light Microscopy; Electron Microscopy;

X-ray Techniques. Ask students to speculate on which technol-

ogy (or technologies) could provide useful information about the

objects on Master 1.1, Searching for Scale. What would make one

technology more useful than another in any given situation?

Students should realize that naked-eye observation is useful only

for relatively large objects and is not useful at all for discerning

cellular and subcellular objects. They also will realize that light

microscopy is useful for looking at cells and resolving some

50

organelles, like the nucleus and vacuoles. Students should know

from material in their texts that electron microscopy is used to pro-

vide details about cells and subcellular structures. Some may have

seen electron micrographs of DNA. Most students know little about

X-ray technologies, although they may have heard of X-ray crystal-

lography as a technique that was used to help resolve the structure

of DNA. If students have ideas about why certain technologies are

better for some tasks than others, write those responses on the

board. Indicate that the reason for having the right tool for the

right task is addressed in Lesson 2.

51

Student

Student L

L essons

esson 1

How Your

Using T Brain Understands

echnology to Study What Your

Cellular Ear

and Hears

Molecular Biology

Lesson 1 Organizer

Activity 1: Technology—What’s It All About?

What the Teacher Does

Procedure Reference

Ask students,

Pages 44–45

• “What is technology?”

Steps 1–2

• “In general, what does technology do for us?”

Focus discussion of technologies relevant to each student’s life.

Pages 45–46

• Ask students to look around the room; what technolo-

Steps 3–5

gies do they see?

• How do these technologies solve problems and make

their lives easier?

• Pick a technology mentioned. Ask students what types of

knowledge were required to develop that technology.

• After discussion, ask students to rethink and refine their

definition of technology.

Tell students to imagine that they live in the Stone Age. Their

Page 46

only garment is ripped and requires mending. Ask,

Steps 6–7

• “How would you mend the garment?”

• “How would your approach to mending the garment

change as time advanced from the Stone Age to the

present?”

• “What new knowledge would allow the development of

new technology?”

Write the words problem and technology on the board. Ask

Page 46

students to use arrows to draw a graphic that represents the

Step 8

relationship they believe exists between a problem and the

technology needed to solve it.

Activity 2: Searching for Scale

What the Teacher Does

Procedure Reference

Ask students,

Page 47

• “How do biological structures, such as cells, organelles,

Step 1

bacteria, and viruses, compare in size with one another?”

• “How do molecules compare in size with biological

structures such as cells, organelles, bacteria, and

viruses?”

52

Tell students that they will investigate the relative sizes of differ-

Pages 47–48

ent biological structures.

Steps 2–5

• Give each student a copy of Master 1.1, Searching for

Scale.

• Work with the class to complete column 3, Size relative

to cell.

• Ask students to define scale based on the information in

columns 2 and 3.

• Ask students if they can visualize the 100,000-fold

difference in size between a cell and a water molecule.

How could they demonstrate this large size difference?

• Ask two students to measure and mark approximately

Pages 48–49

10 m along both the length and width of the classroom.

Steps 6–7

• Tell students that the space defined by 10 m wide, 10 m

in length, and the height of the room is a model for a

typical

cell.

Organize students into pairs.

Pages 49–50

• Give each pair a ruler.

Steps 8–11

• Tell students that they will be searching the classroom

for objects that model the biological structures on Mas-

ter 1.1, Searching for Scale.

• Tell students to use the information provided in the last

three columns of Master 1.1 to help in their search.

• Instruct students to complete the last three columns of

Master 1.1 as they locate appropriate objects.

Ask students to share some of their results with the class.

Page 50

Step 12

= Involves copying a master.

53

Student Lesson 1

Lesson 2

Explore

Explain

Resolving Issues

Overview

At a Glance

This lesson consists of two activities linked by classroom discussion. In

the first activity, which is similar to the game Battleship, students inves-

tigate the concept of resolution and the relationship between probe size

and resolution. The second activity incorporates results from the first

activity and classroom observation and discussion. Students discover that

in order to understand the complete structure of an object, it is necessary

to have information in three dimensions rather than just two.

Major Concepts

Doing research in cellular and molecular biology requires scientists to

identify the right technology (tool) for the job. An important consider-

ation is the technology’s ability to resolve structural details of biological

objects. Two objects can be resolved by using a probe (radiation) of a size

(wavelength) that is not larger than the distance separating the objects.

Generally, the smaller the probe, the greater the structural detail, or

resolution, that results. Detailed structural knowledge about biological

objects requires information obtained in three dimensions.

Objectives

After completing this lesson, students will

• be able to define resolution,

• be able to explain the relationship between probe size and resolution,

and

• be able to explain why information in three dimensions is necessary

to describe the structure of an object.

Teacher Background

See the following sections in Information about Using Technology to

Study Cellular and Molecular Biology:

3.1 Scale (pages 24–25)

3.2 Resolution (pages 25–26)

55

Using Technology to Study Cellular and Molecular Biology

In Advance

Web-Based Activities

Activity

Web Version

1

No

2

Yes

Photocopies

Activity 1 • Master 2.1, Probing for Answers Score Sheet, 1 copy per 2

students; 1 transparency for classroom demonstration

• Master 2.2, Probes, 1 copy per 12 students (see

Preparation)

• Masters 2.3 to 2.8, Probing for Answers—Levels 1–6,

1 copy of each per 12 or fewer students; 2 copies of each

for 13–24 students; 3 copies of each for 25–36 students

Activity 2

• Master 2.9, Solution to Probing for Answers, 1 transparency

( print version only)

Materials

Activity 1 manila folders (1 per group, optional)

Activity 2

• 2 hard-crusted bread rolls, unsliced

• knife to slice bread

• food coloring

• syringe with needle, or 1-mL pipette

Preparation

Activity 1

From Master 2.2, Probes, cut out each 3 × 3, 2 × 2, and 1 × 1 square

(1 copy produces 6 of each size of probe).

Activity 2

Just before the class period in which students will do this activity, inject

a small amount of colored food dye into two locations in each of two

unsliced, hard-crusted bread rolls. One location should be to the right of

center and the other, to the left of center. The same or different dye col-

ors can by used. Injecting the dye can be accomplished several ways to

meet the primary objective, which is to color the inside and not the out-

side of each roll. Use either a syringe with a needle long enough to reach

well into the roll or a carefully inserted 1-mL pipette. Wipe the outside

surface of the needle or pipette to remove any dye solution before insert-

ing it into the roll. It may help to use a sharp object, such as the sharp,

pointed portion of a compass, to make a small hole before inserting a

pipette containing dye. Try not to leave traces of the dye on the outside

of the rolls.

56

If you have Internet access, have at least one computer at the URL http:

//science.education.nih.gov/supplements/technology/student. This is a main menu page from which you can access this activity.

Activity 1: Probing for Answers

Procedure

1.

Begin by stating or writing on the board, “Technology is a means

of extending human potential or of extending human senses.” Ask

students to raise their hands if they agree with this statement.

2.

Ask students to provide justification for their responses. Can

students relate specific technologies to the extension of specific

Assessment:

human attributes or senses?

Steps 1 to 5 are

intended to be a quick

Students will generally agree that technology extends human

method to assess stu-

potential. Obvious examples include the wheel and other trans-

dents’ prior concep-

portation innovations that extend our potential for movement, and

tions about the use of

electronic devices, such as TV, radio, and telephones, that extend

technology in biologi-

our ability to communicate. Microscopes, telescopes, eyeglasses,

cal science.

and contact lenses extend and enhance our sense of vision. Com-

puters and written materials can be seen as ways to extend memory.

There are many other examples.

Tip from the field test: Some students correctly pointed out that

technology is also used to extend animal potential.

3.

Ask students to consider only technologies that have increased

our understanding of living systems. Do they extend any human

attributes? If they do, which attributes are extended?

Students will probably focus on those that extend vision, since

they are the easiest to recognize. Examples could include radar,

eyeglasses, contact lenses, and telescopes. Students also know that

microscopes allow us to see objects that we cannot see with the

naked eye. Students should be familiar with the light microscope,

and many may have heard of electron microscopes. Through figures

in textbooks, they may know X-ray crystallography as a technol-

ogy that helped us “see” the structure of DNA. Other technologies

might be mentioned. Accept all responses and write them on the

board. This is an opportunity to identify students’ current under-

standing of these technologies.

A Gary Larson Far Side cartoon, “Early Microbiologists,” can be

used to engage students. Pictured is a caveman “laboratory,” in

which several cavemen peer intently into Petri dishes filled with

agar. Since they do not have microscopes, they hold the dishes in

various ways, such as very close to the face. One of the cavemen

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Student Lesson 2

Using Technology to Study Cellular and Molecular Biology

imitates binoculars by holding his hands to his eyes. (The cartoon

can be found in several published works, including The Prehistory

of the Far Side, by Gary Larson, copyright 1989 by FarWorks, Inc.,

distributed by Universal Press Syndicate, published by Andrews

McMeel, Kansas City, Kansas.)

4.

Ask students to focus on technologies as tools that allow us to

“see” biological objects (the eye, microscopes of all kinds, and

X-ray techniques). One at a time, ask the following questions:

a.

What technologies would you use to study a whole (intact)

organism and why?

b.

What technologies would you use to study cells and why?

c.

What technologies would you use to study molecules and why?

Accept all reasonable responses, but challenge those that are incor-

rect. Students should understand that no single technology is use-

ful at all levels of organization of biological organisms. In other

words, no single technology is able to resolve structural details

from the intact organism to the molecules that make up that organ-

ism. This discussion introduces students to the idea that there is a

right tool for the job.

5.

Ask students why a single technology cannot provide information

at all levels of organization of biological organisms.

You might remind students that at the conclusion of Lesson 1, they

Content Standard A:

were asked to speculate on what would make one technology more

Identify questions and

useful than another in a given situation. If students need prodding,

concepts that guide

you can ask whether they would use a microscope to study a whole

scientific investiga-

organism, or whether they would use their eyes alone to study mol-

tions.

ecules. While a microscope is required to study single-celled organ-

isms, such as bacteria and protists, most multicellular organisms

can be observed with the unaided eye. High-resolution technolo-

gies, such as X-ray crystallography, are required for investigations

of molecular structure.

6.

Tell students that what makes some technologies better than

others for a given job relates to the concept of “resolution.” Ask

them what resolution means.

Tip from the field test: Students generally had no concept of

resolution as it relates to technologies used in biological science.

Responses often related to resolution of computer monitors, per-

sonal resolve, or New Year’s resolutions.

58

7.

Tell students that they will investigate resolution. Organize the

class into groups of two and then pair two groups.

This activity works best if you have a minimum of six groups so

that each can receive one of the six Masters 2.3 through 2.8.

8.

Ask groups to arrange their seating so that one is directly oppo-

site another:

Allow sufficient room between tables so that groups do not inter-

fere with one another.

9.

Explain to the class that this activity resembles the game Battle-

ship, with which some of them might be familiar. Each group’s

task is to locate and define the shape of an object or objects on

the master held by the opposing group.

Tip from the field test: Field-testing indicated the need to point

out that this activity is not exactly like Battleship. Students do not

“sink” or “destroy” an opposition’s force. Rather, they use the Bat-

tleship strategy to locate and define the shape of a shaded region or

regions on the master held by an opposing group.

10. Give each group a copy of Master 2.1, Probing for Answers Score

Sheet.

Students use this sheet to record hits and misses as they probe for

the location of the opposing group’s shaded region(s).

11. Randomly color several regions on a transparency of Master 2.1,

Probing for Answers Score Sheet. Use this transparency and a

3 × 3 probe from Master 2.2, Probes, to demonstrate how this

activity is done.

a.

Use this probe to locate areas 3 squares by 3 squares on

the transparency. To save time, you may instruct students

to probe only the nine nonoverlapping 3 × 3 regions, as

shown on the following diagram:

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Student Lesson 2

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b.

One group begins by calling out the location of the

3 × 3 area they wish to probe, such as A-C, 1-3.

c.

If the opposing group’s Master (2.3, 2.4, 2.5, 2.6, 2.7,

or 2.8) has a shaded square within the area called, they

indicate this as a hit; if not, a miss.

d.

The first group records the result on their score sheet.

Draw an X in 3 × 3 squares that are misses, and put an

O in the 3 × 3 squares that are hits.

e.

It is then the opposing group’s turn to select an area to

probe, which is then recorded as a hit or a miss.

f.

Groups take turns trying to locate the opposing group’s

shaded squares.

12. Give each group a copy of one master selected from Masters 2.3

to 2.8. Instruct groups to hide this master from their opposing

group.

Make sure that each of these six masters is used by at least one

group. In larger classes, the same master may be used by more than

one group. You may choose to place each master in a manila folder.

Students can use the folder in various ways (for instance, opened

and stood on its edge) to keep their master from being seen by the

opposing group.

13. Give each group a 3 × 3 probe from Master 2.2, Probes. Instruct students to use this probe to locate areas 3 squares by 3 squares

that contain the opposing group’s shaded area(s).

Limit the time allowed for this portion of the activity to no more

than five minutes.

60

14. Ask students whether they believe they have gathered enough

information to specify the exact shape(s) and location(s) of the

opposing group’s shaded object(s).

Make sure students in opposing groups do not share information

about their shaded patterns. Students should realize from look-

ing at their own shaded pattern that the 3 × 3 probe is too large to

identify the shape and location of smaller objects; that is, the large

probe cannot resolve the size and shape of the smaller objects.

15. Ask students what would help them define the shape and loca-

tion of the opposing group’s shaded object(s).

A smaller probe is required.

Tip from the field test: Field-testing indicated the importance of

having students come to this conclusion on their own.

16. Next, give each group a 2 × 2 probe. Groups are to focus on those

areas that were determined to be hits with the larger probe.

Students are to repeat with this probe what they did earlier (see

Step 13 above) and try to determine the structure and location of

the opposing group’s shaded pattern. Limit the time allowed for

this portion of the activity to no more than several minutes.

17. Ask students whether they believe they now have enough infor-

mation to specify the exact shape(s) and location(s) of the oppos-

ing group’s shaded object(s).

Make sure students in opposing groups do not share information

about their shaded patterns. At this point, some students may

believe they have sufficient information to predict the pattern

held by the opposing group. Ask those willing to speculate on the

opposing group’s pattern to provide their justification, especially

how they know that all four squares in a 2 × 2 “hit” region are

shaded.

18. Next give each group a 1 × 1 probe.

Students should focus only on those areas determined to be hits with

the 2 × 2 probe. They should continue to define the structure and loca-

tion of the opposing group’s shaded pattern. Limit the time allowed for

this portion of the activity to no more than several minutes.

19. Ask students if they believe they now have gathered enough

information to specify the exact shape(s) and location(s) of the

opposing group’s shaded objects. Do they need another probe to

complete the task?

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Students should justify their responses. Students cannot know for

sure what the opposing group’s pattern looks like, even though

they see that their own pattern is composed of 1 × 1 squares. If

they speculate that the opposing group’s pattern is constructed

similarly, then no additional probes are required, since the objects

being resolved (the 1 × 1 squares, both shaded and unshaded) are

the same size as the final probe. Importantly, the final probe is not

larger than the objects being resolved. If students believe that addi-

tional probes are required, they should justify this based on what

they believe to be the size of the objects being resolved (shaded and

unshaded). Their suggestion for an additional probe should indi-

cate a probe size no larger than that of the objects being resolved.

No matter what the response, ensure that students derive a general

relationship between probe size and the size of the objects being

resolved before proceeding. They should be able to explain that

the size of the probe should be no larger than the objects being

resolved.

20. Have opposing groups confirm that after using the series of three

probes, they were able to determine the correct pattern on one

Assessment:

another’s master.

Listening to students

explain their answers,

defend their reason-

Discussion Questions

ing, and modify their

1.

Why not use the smallest probe first?

responses after listen-

ing to other students

explain their logic will

A similar question is, Is there an advantage to using larger probes

help you assess stu-

first and then using smaller probes? The larger probes allowed the

dents’ understanding

students to quickly identify the general location of the object(s)

being investigated. In some cases, even information about struc-

of resolution.

ture, albeit crude, can be obtained. Remind students of the pro-

cedure they follow when using a light microscope. They first use

the lowest magnification to locate the object of interest and then

switch to a higher magnification to gain more information. Using

the smallest possible probe first can be time consuming and expen-

sive. In some cases, using the smallest available probe also can be

inappropriate; for example, when the probe is very much smaller

than the objects being resolved. As an example, consider the time

and expense involved in using an electron microscope rather than a

light microscope to count yeast cells or to assess fruit fly traits in a

genetics experiment.

2.

On the board, write these wavelengths:

•

visible light, 4 to 7 × 10–7 m;

•

electrons, 2.7 to 0.9 × 10–10 m; and

•

X-rays, 1 × 10–8 to 1 × 10–11 m.

Refer to Master 1.1, Searching for Scale, and ask students which 62

6

of these they think would be appropriate probes (that is, provide

the appropriate level of resolution) for the objects listed.

Visible light could be used to resolve cells, bacteria, and mitochon-

dria. Longer-wavelength electrons are potential probes for viruses,

small cell organelles such as ribosomes, and large molecules such

as proteins. Shorter-wavelength electrons and short-wavelength

X-rays are potential probes for molecules, even small ones like glu-

cose. They also may be used to resolve adjacent atoms in molecules

(which requires probes smaller than 2 × 10–10 m).

Teacher note: Whether or not a probe is useful in a given situation

also depends on whether the technology actually exists to make

use of the probe. For instance, are appropriate sample-preparation

techniques available? Are appropriate sample handling technologies

available (for example, can the sample be rotated if necessary, and

in a way that does not interfere with the rest of the procedure)?

Can the probe be focused sufficiently? Is there technology to view

and evaluate the results of such analyses?

Activity 2: More Than Meets the Eye

1.

Begin by holding one of the bread rolls up to the class. Make sure

that no dye is showing. Ask students to describe what they see.

Students will recognize the object, and they may describe it by not-

ing its color, shape, and apparent external texture. They should

indicate that the roll is a three-dimensional object.

2.

Do students have maximum information about the roll? Is there

anything they do not know about the bread roll from just looking

at it?

Student responses will vary from, “Is it tasty?” and “Where does it

come from?” to “What is inside?” Some students may realize that

although they might have made an assumption about the roll’s inte-

rior (for example, it is just plain bread), they actually know noth-

ing about what is under the crust.

3.

Focus discussion on what is inside the bread roll. Ask students

how they would get that information.

Students will suggest cutting

or tearing the roll.

4.

Slice the roll to reveal the

presence of dye in one of

the two dye locations. Hold

the roll so the class can see

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the two cut edges. Do the students now feel they have complete

information about this object? If not, what questions do they have?

Even though they know there is a dyed region inside the roll, stu-

dents should realize that they do not know what this region looks

like. What is the shape of the dyed region and how far does it

extend in any given direction? Is there only a single dyed region, or

are there multiple regions? If there is more than one dyed region, is

it the same color as the region they can see?

Tip from the field test: Some students suggested cutting the roll as

one would if making a sandwich. The second bread roll is helpful if

this possibility is raised.

5.

Ask students how they could obtain information to answer these

questions.

A simple approach would be to make additional slices in the roll.

Students may suggest more exotic means (for example, use a fiber

optic light source connected to a minivideo device to view the roll’s

interior on a remote screen). If suggestions fall in the latter cat-

egory, congratulate students for their ingenuity. Ask them to think

about how to gain the information required quickly and using

simple, available technology. In the end, focus student attention on

increasing the number of slices. This requires only a knife and can

be done quickly.

6.

Ask the students how many slices would be required to define

the dyed region(s) in the roll’s interior. What are their consider-

ations in providing an answer to this question?

The actual number of slices that the students believe is correct is

not the important issue. If students do provide a specific answer,

ask them to justify it. It is important for them to understand the

following. First, multiple slices are required to define the object’s

properties. The size of the slices will determine the resolution used

to define the object’s properties. Thicker slices will provide less res-

olution, just as the 3 × 3 probes provided low resolution in Activity

1. Thinner slices will provide greater resolution, just as the 1 × 1

probes did in Activity 1.

7.

Ask students to have their group’s Master 2.3 to 2.8 available.

Explain that the “level” designation below the grid (Level 1, 2, 3,

4, 5, or 6) on the master indicates the location of a slice through

an object.

Level 1 is the top slice, followed by 2, 3, 4, 5, and 6 (at the bot-

tom).

64

8.

Ask students to visualize their pattern in three dimensions by

imagining that their shaded pattern represents the top of a stack

of gray blocks. Their level is a slice two blocks thick.

9.

Ask the groups to share their data (that is, the location of the

shaded regions) and try to reconstruct the three-dimensional

object that has been cut into six slices.

Do not provide additional guidance. Give students about five min-

utes to do this. Students may or may not be able to reconstruct the

object in this time.

For those using the Web version of this activity, proceed as

follows:

10. Were students able to arrive at a solution? What might

have made the task of reconstructing the object in three dimen-

sions easier?

Content Standard E:

Identify a problem or

Students might suggest that a computer could provide the technol-

design an opportunity.

ogy to make reconstruction easier.

Content Standard E:

11. Have students proceed to the URL http://science.education.nih.gov/

Implement a proposed

supplements/technology/student. Students should then click on the solution.

link to “Lesson 2—Solution to Probing for Answers.” This brings

up the unit’s desktop, from which students can access this activity. Content Standard A: 12. Students can enter their data by first selecting a level (1 to 6) and Scientists rely on tech-then clicking on the squares they determined to be shaded. The

nology to enhance

reconstructed object will appear as data are entered.

gathering and manipu-

lating data.

It may be easier and less time consuming for the teacher to enter

the data provided by the students.

For those using the print version of this activity, proceed as

follows:

10. Show students a transparency of Master 2.9, Solution

to Probing for Answers. Were they able to arrive at this

Content Standard E:

solution? What might have made their task easier?

Identify a problem or

design an opportunity.

Some students do well thinking in three dimensions, and others do

not. Many may recognize the need for additional technology, such

as a computer and appropriate software, to make the job of recon-

struction easier. Even a simple technology, such as wooden blocks

or Legos, could have been used to construct a three-dimensional

model of the intact object.

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Discussion Question

1.

As a follow-up, ask students, “Have these activities expanded

your understanding of technology? If they have, how?”

Assessment:

Activity 1 demonstrates the use of multiple probes to achieve dif-

This question allows

ferent levels of resolution. It also demonstrates that the right tool,

students to integrate

in this case a probe of appropriate size, must be selected to solve a

the information they

problem (resolving the structure of an unknown object). Therefore,

have learned in the

students should realize that there is an appropriate technology for

first two lessons and

a given problem (that is, the right tool for the job). Activity 2 dem-

refine their under-

onstrates that solutions to a problem may involve more than one

standing of what tech-

technology (the use of slices to determine the structure of a three-

nology is.

dimensional object and technologies to collect and analyze the data).

66

Lesson 2 Organizer: Web Version

Activity 1: Probing for Answers

What the Teacher Does

Procedure Reference

State or write on the board, “Technology is a means of extend-

Pages 57–58

ing human potential or of extending human senses.”

Steps 1–3

• Ask students if they agree with this statement.

• Ask students to provide justification for their responses.

Can they relate specific technologies to the extension of

specific human attributes or senses?

• Ask students to consider technologies that have

increased our understanding of living systems.

o Do they extend any human attributes?

o If they do, which attributes are extended?

Ask students to focus on technologies (the eye, microscopes,

Page 58

X-ray techniques) that allow us to see biological objects. Ask,

Steps 4–6

• “What technologies would you use to study a whole

organism and why?”

• “What technologies would you use to study cells and

why?”

• “What techniques would you use to study molecules and

why?”

• “Why can’t a single technology provide information at all

levels of organization of biological organisms?”

Introduce the concept of resolution. Ask students what resolu-

tion means.

Tell students that they will investigate resolution. Organize the

Pages 59–60

class into groups of two and then pair two groups.

Steps 7–11

• Arrange seating so that one group sits opposite the

other.

• Explain that the activity resembles the game Battleship.

• Each group’s task is to locate and define the shape of

an object or objects on the master held by the opposing

group.

• Give each group a copy of Master 2.1, Probing for

Answers Score Sheet.

• Use a transparency of this master to demonstrate how

the activity is done.

67

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Begin the activity.

Pages 60–62

• Give each group one master selected from Masters 2.3

Steps 12–20

to 2.8, Probing for Answers—Levels 1–6.

• Give each group a 3 × 3 probe from Master 2.2, Probes.

Instruct students to use this probe to locate areas 3

squares by 3 squares that contain the opposing group’s

shaded object(s).

• After five minutes, ask students if they have enough

information to specify the exact shape(s) and location(s)

of the opposing group’s shaded object(s).

• Ask students what would help them define the shape

and location of the opposing group’s shaded object(s).

• Give each group a 2 × 2 probe and ask them to refine

their search with this probe.

• After several minutes, ask students if they believe they

now have enough information to specify the exact

shape(s) and location(s) of the opposing group’s shaded

object(s).

• Give each group a 1 × 1 probe and ask them to refine

their search with this probe.

• After several minutes, ask students if they believe they

now have enough information to specify the exact

shape(s) and location(s) of the opposing group’s shaded

object(s). Do they need another probe to complete their

task?

• Have opposing groups confirm that after using the series

of three probes, they were able to determine the correct

pattern on one another’s master. Proceed to discussion

questions.

Activity 2: More Than Meets the Eye

What the Teacher Does

Procedure Reference

Hold a bread roll into which you have inserted food dye up to

Pages 63–64

the class.

Steps 1–6

• Ask students to describe what they see.

• Is there anything about the roll they do not know from

just looking at it?

• Focus discussion on what is inside the roll and ask stu-

dents how they would get that information.

• Slice the roll to reveal the dye.

• Ask students if they feel that they now have complete

information about the object.

• What additional questions do they have and how could

they get the answers?

• How many slices are required to define the dyed

region(s) in the roll’s interior? Focus discussion on

resolution.

68

Ask students to have their Master 2.3 to 2.8 available.

Pages 64–65

• Explain that the “level” designation on the master indi-

Steps 7–10

cates the location of a slice through an object (1 at the

top to 6 at the bottom).

• Ask students to visualize their pattern in three dimen-

sions by imagining that their shaded pattern represents

the top of a stack of grey blocks. Their level is a slice two

blocks thick.

• Ask the groups to share their data (that is, the location

of the shaded regions) and try to reconstruct the three-

dimensional object that has been cut into six slices.

• Ask if students were able to arrive at a solution. What

might have made their task easier?

Have students click on “Lesson 2—Solution to Probing for

Page 65

Answers” and then click on the link to “Solution to Probing

Steps 11–12

for Answers.” Have students enter their data to reconstruct the

object.

= Involves copying a master.

= Involves using the Internet.

= Involves using a transparency.

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Lesson 2 Organizer: Print Version

Activity 1: Probing for Answers

What the Teacher Does

Procedure Reference

State or write on the board, “Technology is a means of extend-

Pages 57–58

ing human potential or of extending human senses.”

Steps 1–3

• Ask students if they agree with this statement.

• Ask students to provide justification for their responses.

Can they relate specific technologies to the extension of

specific human attributes or senses?

• Ask students to consider technologies that have

increased our understanding of living systems.

o Do they extend any human attributes?

o If they do, which attributes are extended?

Ask students to focus on technologies (the eye, microscopes,

Page 58

X-ray techniques) that allow us to see biological objects. Ask,

Steps 4–6

• “What technologies would you use to study a whole

organism and why?”

• “What technologies would you use to study cells and

why?”

• “What techniques would you use to study molecules and

why?”

• “Why can’t a single technology provide information at all

levels of organization of biological organisms?”

Introduce the concept of resolution, Ask students what resolu-

tion means.

Tell students that they will investigate resolution. Organize the

Pages 59–60

class into groups of two and then pair two groups.

Steps 7–11

• Arrange seating so that one group sits opposite the

other.

• Explain that the activity resembles the game Battleship.

• Each group’s task is to locate and define the shape of

an object or objects on the master held by the opposing

group.

• Give each group a copy of Master 2.1, Probing for

Answers Score Sheet.

• Use a transparency of this master to demonstrate how

the activity is done.

70

Begin the activity.

Pages 60–62

• Give each group one master selected from Masters 2.3

Steps 12–20

to 2.8, Probing for Answers—Levels 1–6.

• Give each group a 3 × 3 probe from Master 2.2, Probes.

Instruct students to use this probe to locate areas 3

squares by 3 squares that contain the opposing group’s

shaded object(s).

• After five minutes, ask students if they have enough

information to specify the exact shape(s) and location(s)

of the opposing group’s shaded object(s).

• Ask students what would help them define the shape

and location of the opposing group’s shaded object(s).

• Give each group a 2 × 2 probe and ask them to refine

their search with this probe.

• After several minutes, ask students if they believe they

now have enough information to specify the exact

shape(s) and location(s) of the opposing group’s shaded

object(s).

• Give each group a 1 × 1 probe and ask them to refine

their search with this probe.

• After several minutes, ask students if they believe they

now have enough information to specify the exact

shape(s) and location(s) of the opposing group’s shaded

object(s). Do they need another probe to complete their

task?

• Have opposing groups confirm that after using the series

of three probes, they were able to determine the correct

pattern on one another’s master. Proceed to discussion

questions.

Activity 2: More Than Meets the Eye

What the Teacher Does

Procedure Reference

Hold a bread roll into which you have inserted food dye up to

Pages 63–64

the class.

Steps 1–6

• Ask students to describe what they see.

• Is there anything about the roll they do not know from

just looking at it?

• Focus discussion on what is inside the roll and ask stu-

dents how they would get that information.

• Slice the roll to reveal the dye.

• Ask students if they feel that they now have complete

information about the object.

• What additional questions do they have and how could

they get the answers?

• How many slices are required to define the dyed

region(s) in the roll’s interior? Focus discussion on

resolution.

71

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Ask students to have their Master 2.3 to 2.8 available.

Pages 64–65

• Explain that the “level” designation on the master indi-

Steps 7–10

cates the location of a slice through an object (1 at the

top to 6 at the bottom).

• Ask students to visualize their pattern in three dimen-

sions by imagining that their shaded pattern represents

the top of a stack of grey blocks. Their level is a slice two

blocks thick.

• Ask the groups to share their data (that is, the location

of the shaded regions) and try to reconstruct the three-

dimensional object that has been cut into six slices.

• Show students a transparency of Master 2.9, Solution to

Probing for Answers.

• Ask if students were able to arrive at this solution. What

might have made their task easier?

= Involves copying a master.

= Involves using a transparency.

72

Lesson 3

Explore

Explain

Putting Technology

Elaborate

to Work

Overview

At a Glance

This lesson consists of a single activity with three parts in the Web ver-

sion and four parts in the print version. It will take two days to complete.

The lesson provides an opportunity for students to investigate some tech-

nologies that have advanced our understanding of cellular and molecular

biology. Probe size, resolution, and using the right tool for the job are

emphasized. Students are presented with a fictitious scenario involving

the discovery of a muscle-wasting disease. As members of a medical and

scientific team, they must choose a technology to use—light microscopy,

transmission electron microscopy, cryo-electron microscopy, or X-ray

crystallography—to investigate the disease. They answer questions such

as, What is the infectious agent, how does the infectious agent cause dis-

ease, and is there a drug to treat or prevent the disease?

Major Concepts

Technologies that differ in their resolving capabilities provide different

information about the structure of an object. Solving a problem requires

an appropriate technology or series of technologies. Technology provides

valuable tools for solving scientific problems relevant to human health.

Objectives

After completing this lesson, students will

• be able to explain the use of technologies based on their resolving

power,

• be able to explain how technologies are used to solve scientific and

health-related problems,

• be able to explain the concept of using the right tool for the job, and

• be able to develop a multistep research plan in which hypotheses are

formulated, data are gathered and interpreted, and new questions are

asked.

Teacher Background

See the following sections in Information about Using Technology to

Study Cellular and Molecular Biology:

3 Scale and Resolution (pages 24–26)

4 Major Techniques in the Study of Cellular and Molecular Biology

(pages 26–35)

73

Using Technology to Study Cellular and Molecular Biology

In Advance

Web-Based Activities

Activity

Web Version

1

Yes

Photocopies

For class- • Master 3.1, Memo from the Director, Global Science and

rooms

Health Organization, 1 copy per group

using the • Master 3.2, Research Plan, 1 copy per student and

Web

1 transparency

version

• Master 3.3, Example of a Research Plan, 1 transparency

of this

• Master 3.4, Drug Discovery Evaluation Form, 1 copy per

activity:

student

• Master 3.1, Memo from the Director, Global Science and

For class- Health Organization, 1 copy per group

rooms

• Master 3.2, Research Plan, 1 copy per student or

using the 1 transparency for class

print

• Master 3.3, Example of a Research Plan, 1 transparency

version

• Master 3.5, Available Technologies, 1 transparency

of this

• Master 3.6, Science Reference Manual, 1 copy per group

activity:

• Master 3.7, Muscle Protein Structures Determined by X-Ray

Crystal ography, 1 copy per group or 1 transparency for class

Materials

Activity 1 none required

Preparation

For classrooms using the Web version of this activity:

Verify that computer lab is reserved for two consecutive class periods or

that classroom computers are ready to use. To save time, have comput-

ers at the URL http://science.education.nih.gov/technology/student. This is a main menu page from which this activity can be accessed.

For classrooms using the print version of this activity:

No preparations needed.

Procedure

For classrooms using the Web version of this activity.

Teacher note: This activity allows students to enter a virtual

laboratory in which they use microscopic techniques and X-

ray crystallography to solve a problem. The activity requires students to

74

view and interpret data. An essential part of it is having students develop

a logical research plan based in part on what they learned earlier in this

module about scale and resolution. They should formulate hypotheses

that can be tested with the technologies available to them.

Part 1, Solving the Problem

1.

Divide the class into groups of two students each, and give each

group a copy of Master 3.1, Memo from the Director, Global Sci-

ence and Health Organization.

2.

Ask students to read the memo and note the questions they are

instructed to answer.

This memo also appears when students access the activity on the

Web. Students can retain the printed memo to remind themselves

of the questions they are to answer.

3.

Explain that students will begin by formulating a research plan.

They will develop hypotheses that can be tested in their virtual

laboratory.

If necessary, remind students that hypotheses are statements that

predict a result and are testable experimentally.

4.

Ask students to proceed to http://science.education.nih.gov/

supplements/technology/student. They should click on the link to

“Lesson 3—Putting Technology to Work.” This brings up the

unit’s desktop, from which this activity can be accessed.

After clicking on the activity link on the desktop, the memo from

the director appears. After students close the memo, each of the

four available technologies is highlighted. Note: Students should

not yet click on a technology.

5.

Explain that students have resources available to them, includ-

ing various technologies and reference materials. Ask students to

click on the link to “Reference Manual.”

Briefly review the contents of the Reference Manual with the stu-

dents.

Tip from the field test: Field-testing has indicated that it is very

useful for teachers to introduce students to the Science Reference

Manual early in this activity (see Teacher note 1 on page 79). This

resource contains valuable information to help students formulate

their hypotheses, including the sizes of biological structures and

resolution limits of various technologies, as well as details about

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Student Lesson 3

How Your

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Cellular Ear

and Hears

Molecular Biology

unfamiliar technologies, blood cells, muscle cells, and pathogens

and how they cause disease. At a minimum, you should introduce

students to the table of contents of the Science Reference Manual,

point out which topics are links to more information, and use one

link to show students the kind of information provided.

6.

Ask students how they will begin their studies. What should

they do first? Encourage student participation and accept all

responses.

Teacher note: Even though students are in pairs, work with the

class as a whole through Step 15 to help them understand the pro-

cess.

This question is purposely vague. Its intent is to engage the stu-

dents and initiate creative thinking. Student responses may vary

considerably. Some students may suggest beginning at the lowest

level of resolution, the eye, and visually confirming the presence

of ill individuals. They may suggest talking with healthy and ill

individuals to gain clues about the nature of the disease. They may

want more details about symptoms. Indicate to students that while

gaining additional information by talking with affected and unaf-

fected individuals might be helpful, there is no time to travel. They

need to get down to business and begin investigating the issues

raised in the director’s memo.

7.

Direct students to the first question in the director’s memo.

Choosing from the available technologies and using tissue sam-

ples from affected and unaffected individuals, how can they con-

firm the presence of disease at the cellular level in the affected

population?

Students have muscle and blood samples available for study. Stu-

dents should reason that light microscopy can be used to look

for the presence of abnormal muscle cells in affected individuals.

Unaffected individuals should have normal muscle cells. Students

should provide a reason for wanting to look at any other tissue

samples.

8.

Ask students, “Why would you use light microscopy to confirm

the presence of disease?”

Students should know that cells are too small to be seen by the

naked eye, although they can be seen easily with a light micro-

scope. If necessary, ask students to think about the information on

Master 1.1, Searching for Scale (the size of a cell) and what they

discovered in Lesson 2, Activity 1: Probing for Answers (start with

the largest probe, in this case visible light).

76

9.

After deciding on a starting point (light microscopy), students

should begin constructing their detailed research plan. Give each

student a copy of Master 3.2, Research Plan.

Master 3.2 presents an example of how a research plan can be orga-

Content Standard A:

nized. It is important for students to see how information flows

Identify questions and

as an investigation proceeds and how what is done at one step

concepts that guide

depends on results from previous steps.

scientific investiga-

tions.

10. Use the transparency of Master 3.2 to demonstrate how the

research plan is constructed. Use Master 3.3, Example of a

Content Standard A:

Research Plan, as your guide.

Design and conduct a

scientific investigation.

11. In the space next to the statement, “To answer the question,”

write the question, Is there evidence of disease at the cellular

level (in muscle cells)? Ask students to help you determine

which technology to use to answer this question.

Students should choose to begin their studies with light micros-

copy to look for the presence of abnormal cells in the muscle tissue

of affected individuals. Write this response in the space next to the

statement, “I will use this technology.”

12. Ask students to respond to the statement, “I chose this technol-

ogy because.”

Students should have reasoned that cells are too small to be seen

with the naked eye but can be seen easily using a light microscope.

In other words, the resolution of a light microscope is sufficient to

see individual cells. Record the response on the transparency.

13. Ask students to state a hypothesis.

There is (or is not) evidence of disease in muscle cells.

14. Ask students what two results they would expect.

Either abnormal muscle cells will be seen in affected individuals or

they will not. Record this response on the transparency.

15. Ask students what question they would answer next if they

observe abnormal muscle cells in affected individuals.

They would proceed to Question 2 on Master 3.1, Memo from the

Director, Is the disease caused by an infectious agent? Record this

response on the transparency.

16. Ask students what question they would answer next if they do

not observe abnormal muscle cells in affected individuals.

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and Hears

Molecular Biology

There is no single response to this question. Students can use their

imagination.

Encourage students to use the Science Reference Manual to learn about

muscle and blood cells. Examples of normal muscle and blood cells

are included in the reference material. Information about the size

of cells, bacteria, and viruses is also provided, as well as the various

technologies students will investigate in this activity.

17. Ask students to complete all tasks except those dealing with dis-

covery of a drug to treat the disease (Question 6 on Master 3.1,

Memo from the Director, Global Science and Health Organization).

18. Instruct students to begin their studies. They should make care-

ful observations at each step and record all of their observations.

They should follow their research plan.

Circulate among groups as students work. Ensure that students are

proceeding according to a rational plan they have developed. You may

want to quiz students about why they selected a specific technology,

what they hoped to see, how they interpret what they did see, or why a

technology is appropriate for solving a specific problem.

Teacher notes:

1. Selecting a technology activates a short animation. For example, after

clicking on the light microscope, the animation changes from a view of

the whole instrument to the view students would have looking through

the eyepiece. Then, a small window opens over an interactive screen.

This window contains information about the samples available for inves-

tigation, such as what the sample is (for instance, tissue or protein), and

the source of the sample (that is, from a person with the disease or from

an unaffected individual). Samples are coded, and students should record

the coding information.

2. The light microscope and the transmission electron microscope are

interactive. Students should begin by selecting a sample and adjust-

ing the brightness by moving the brightness slider. Magnification of the

sample can be changed. Students can move most cell and tissue images

up and down and to the left and right. Students may take a snapshot of

a field they are viewing by clicking on the “View Snapshots.” Clicking

on an individual snapshot produces a larger image that can be compared

with another on-screen image (that is, an image on the microscope or an

image in the Reference Manual). The “View Snapshot” window may be

moved to allow easier comparison of images. Up to 12 snapshots may be

stored.

3. Using the cryo-EM, students should click on “Affected” and “Unaf-

fected.” They should record their observations of what appears in the

78

electron microscope (left monitor) and in the three-dimensional recon-

struction (right monitor).

4. After clicking on “X-ray Crystallography,” students see a detailed

animation of the process. We indicate that the data were obtained from

three different orientations of the protein crystal, which is far fewer than

the thousands of different orientations actually used in a research labora-

tory. Students begin by making observations of the X-ray crystallography

patterns that appear on screen. All that students—or scientists, for that

matter—can judge at this point is that the patterns for the affected and

unaffected proteins are different from one another for each orientation.

Making sense of these data requires processing by high-speed computers

using specialized software. Finally, students compare three-dimensional

models of the affected and unaffected proteins. They should use the

slider to rotate the proteins and record their observations of the differ-

ences and similarities of the proteins’ structures.

19. When students have completed their work and answered Ques-

tions 1 through 5 on Master 3.1, Memo from the Director, Global

Science and Health Organization, reconvene the class.

20. One at a time, have groups share their findings with the rest of

the class.

Content Standard A:

Formulate and revise

Presentations need not be long. However, students should demon-

scientific explanations

strate an understanding of scale, resolution, and selecting the right

and models using

tool for the job. Members of each group should share the respon-

logic and evidence.

sibilities of presenting the group’s information. Students should be

encouraged to question the hypotheses, research plans, and inter-

Content Standard A:

pretations of others. Remind students that science is a collaborative Recognize and analyze process in which scientists must be able to support their ideas.

alternative explana-

tions and models.

Teacher notes:

Content Standard A:

1. The Science Reference Manual contains information that is very help-

Communicate and

ful to students, and they should consult it early in their investigations.

defend a scientific

For instance, students can view light micrographs of normal muscle.

argument.

They will also find information on two common pathogens, bacteria and

viruses, thus limiting the pathogens they search for. Additionally, key

information about technologies is presented.

2. Students should reason that light microscopy can be used to look

for the presence of abnormal muscle cells in affected individuals. Stu-

dents generally know that cells are too small to be seen by the naked eye,

although they can be seen easily with a light microscope. If necessary,

ask students to think about the information on Master 1.1, Searching for

Scale, (the size of cell) and what they discovered in Lesson 2, Activity

1: Probing for Answers (start with the largest probe, in this case visible

light). In this activity, unaffected individuals have normal muscle cells.

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Individuals susceptible to disease have abnormal muscle cells.

3. The Science Reference Manual lists two common pathogens: bacte-

ria and viruses. Students should focus on the 10- to 100-fold difference

in size between bacteria and viruses. Light microscopy can be used to

resolve bacteria, but not viruses. Students should understand that they

are following a plan analogous to the one developed in Lesson 2. They

are starting with the largest probe available (visible light) to find out

about the largest possible structures that can be resolved.

4. No bacteria are visible in either muscle or blood samples. Therefore,

students should use transmission electron microscopy to see whether

viruses are present in any of the tissue samples. Viruses are readily visible

with this technique, which uses a probe (electrons) that is smaller than

the probe they used initially (visible light).

5. Transmission electron microscopy demonstrates the presence of

viruses in blood and muscle tissue samples from one affected and one

unaffected individual. A second set of unaffected blood and muscle sam-

ples does not contain viruses. This observation is a key finding for this

activity, although it may be confusing to some students. How do students

interpret the presence of virus and the absence of disease? How might

this relate to how the virus produces disease in susceptible individuals?

They can consult their Science Reference Manual for helpful information.

A possible reasoned scenario is 1) virus is present in muscle tissue of

both affected and unaffected individuals because the virus binds to a pro-

tein receptor in that tissue, 2) the virus nucleic acid codes for a protein

produced by the muscle cells, 3) the virus protein binds to a key muscle

protein in cells of affected individuals, which causes the disease, 4) the

virus protein does not bind to the muscle protein in cells of unaffected

individuals, 5) the affected muscle protein has a different structure from the unaffected protein, and 6) this difference in structure allows the

affected muscle protein to interact with the virus protein.

6. On the basis of the scenario presented above, a hypothesis might be

as follows: the structure of the affected muscle protein is different from

that of the unaffected muscle protein. An extension of this hypothesis is

that the virus protein binds to the affected muscle protein and not the

unaffected muscle protein because of differences in structure between the

two muscle proteins.

7. On the basis of the scenario presented above, students can use cryo-

EM to generate a three-dimensional reconstruction of the virus attached

to the muscle to see whether the virus attaches to affected muscle fibers

and not unaffected muscle fibers, and they can use X-ray crystallography

to compare the structures of affected and unaffected muscle proteins.

80

8. To students—and to trained scientists, as well—the X-ray crystal-

lography patterns are a collection of spots that do not themselves present

a clear and obvious picture of a molecule’s structure. Students can note

that the patterns differ from one another in spot location and intensity.

They should understand that each pattern is unique because the structure

being investigated is unique; that is, different patterns are produced both

by different orientations of the same molecule and by different molecules.

Students should also see the value of computer technology in providing

three-dimensional molecular structure from a series of X-ray crystallogra-

phy patterns. Please note that many more than three X-ray crystallogra-

phy patterns are required to produce a three-dimensional structure. The

process has been simplified for this activity.

9. Students should evaluate how the structure of the affected muscle

protein compares with the unaffected muscle protein. The only visible

difference between the two proteins is seen in the view along the z-axis

(that is, from the top looking down). The affected muscle protein has an

opening that is not present in the unaffected muscle protein.

Part 2, Applying Technology . . . Again

1.

On behalf of the Global Science and Health Organization, thank

students for their efforts. They have provided answers to some

important questions. However, one very important question

remains: Is there a drug to treat or prevent the disease?

Content Standard A:

Scientists conduct

2.

Ask students how the structural data on the affected and unaf-

investigations for a

fected muscle proteins, obtained by X-ray crystallography, sug-

wide variety of rea-

gest a way that the virus could cause the disease.

sons, such as to dis-

cover new aspects

Accept all responses. It is possible that the affected muscle protein

of the natural world,

can interact with the virus protein because its structure is different

to explain observed

from that of the unaffected muscle protein. Students might wonder

phenomenon, or to

how this interaction could occur. They might speculate that the

test conclusions of

virus protein interacts with parts of the affected muscle protein

prior investigations or

around the opening that exists. It also may be that the virus protein predictions of current interacts with some other region of the affected muscle protein.

theories.

Alternatively, students may hypothesize that the virus causes the

hole in the affected muscle protein. In other words, this action

of the virus produces a muscle protein of changed structure and,

therefore, changed function.

3.

How might a drug be used to treat the disease?

This is another opportunity for students to relate structure to func-

tion. They might reason that the affected muscle protein inter-

acts with the virus protein and not the unaffected muscle protein

because the two muscle proteins have different structures. This

81

Student Lesson 3

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Molecular Biology

difference appears to be characterized primarily by an opening

in the affected muscle protein. Therefore, perhaps a drug can be

developed to change the affected muscle protein’s structure to one

more like the unaffected muscle protein. A simple possibility is to

develop a drug to close the opening. Students may suggest other

possibilities as well. Do not limit their thinking or try to guide the

discussion one way or another.

4.

Direct student groups to their computers. Tell them that the

director of the Global Science and Health Organization has

requested that they evaluate four new drugs that are believed to

have potential to treat the disease.

5.

Give each student a copy of Master 3.4, Drug Discovery Evalua-

tion Form. They should use this form to record their observations and interpretations.

6.

Ask students to click on the link “Drug Discovery Laboratory” on

the unit’s desktop.

A memo appears that gives students the instructions for this activ-

ity. Students compare the unaffected muscle protein with a complex

formed by combining a drug molecule with the affected muscle

protein. Four different drug molecules are available. When students

close the memo, a short animation comes on that leads to a screen

on which appear the unaffected protein, the affected protein, and

the four drug molecules. Students can make observations about

their structures. Clicking on a drug molecule attaches that drug

to the affected protein. Students should use the slider to rotate the

two proteins and compare their structures.

The instructions to students are purposely general. Students should

conclude that the drugs have been designed such that they either

do or don’t convert the structure of the affected muscle protein to

one more like the unaffected protein. Students will observe that

none of the drugs interacts with the affected muscle protein to form

a structure that is exactly the same as the unaffected muscle pro-

tein. This, too, is purposeful and is intended to stimulate student

thinking.

Depending on the class time you have available, you can assign

groups all four molecules to evaluate or a limited number of mol-

ecules (one or two) to evaluate.

Part 3, Wrapping It Up

1.

Reconvene the class. Ask groups to share their drug evaluations.

What were the drugs apparently designed to do? Do any drugs

show promise for treating the disease?

82

This discussion allows students to share thoughts about what they

have done. They should focus on results and interpretations. Stu-

dents should understand that the path to solving a scientific prob-

lem is long and complex and that technology plays a key role in the

process. They also come to realize that there are not always neat

solutions to problems.

2.

Instruct students to prepare a report that summarizes their work.

They are to present their group’s work, from development of a

research plan to drug discovery. It is acceptable for students to add

Content Standard A:

their own touches to the group effort, based on class discussions

Formulate and revise

and further reflection. They should focus on

scientific explanations

• justifying their choice of technology to solve specific problems,

and models using

• demonstrating an understanding of specimen size and resolu-

logic and evidence.

tion, and

• indicating a logical flow for using technologies of increasing

resolution to solve problems.

For classrooms using the print version of this activity

Teacher note: The print version of this activity is a “thought”

activity. It does not make use of the graphics found in the Web

activity, since these graphics do not always reproduce well. This ver-

sion of the activity is more open-ended than the Web version. It allows

students more latitude in formulating a research plan, since they are not

restricted by available resources. Most important in this activity is the

students’ reasoning. Why do they propose to use a given technology?

What results do they expect? How will this lead them to the next step in

their plan? Students work in groups to increase interaction and collabo-

ration.

Part 1, What Is It?

1.

Divide the class into groups of three or four students each, and

give each group a copy of Master 3.1, Memo from the Director,

Global Science and Health Organization.

2.

Ask students to read the memo.

3.

Show students the transparency of Master 3.5, Available Technologies.

Tell students that to help them answer the questions raised by the

director of the Global Science and Health Organization, the fol-

lowing technologies are available: observation by naked eye, light

microscopy, transmission and cryo-electron microscopy, and X-ray

crystallography. Remind them (as stated in the memo) that tissue

samples from affected and unaffected individuals will be available.

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4.

Give each group a copy of Master 3.6, Science Reference Manual.

Explain to students that as scientists, they need reference materi-

als to help them develop a logical and realistic research plan.

Tip from the field test: Field-testing indicated that it is very useful

for teachers to introduce students to the Science Reference Manual

early in this activity (see Teacher note 1 on page 79). This resource

Content Standard A:

contains valuable information to help students formulate their

Design and conduct a

hypotheses, such as sizes of biological structures and resolution

scientific investigation.

limits of various technologies. It also contains information about

unfamiliar technologies, such as X-ray crystallography, as well as

about blood cells, muscle cells, and pathogens and how they cause

disease. At a minimum, you should introduce students to the Table

of Contents of the Science Reference Manual and point out the

information provided there.

5.

Ask students how they will begin their studies. What should

they do first? Encourage student participation and accept all

responses.

Teacher note: Even though students are in smaller groups of three

or four, work with the class as a whole through Step 14 to help

them understand the process they will follow.

This question to students is purposely vague. Its intent is to engage

the students and their imagination. Responses may vary consid-

erably. Some students may suggest beginning at the lowest level

of resolution, the eye, and visually confirming the presence of ill

individuals. They may suggest talking with healthy and ill individu-

als to gain clues about the nature of the disease. They may want

more details about symptoms. Indicate to students that while gain-

ing additional information by talking with affected and unaffected

individuals might be helpful, there is no time to travel. They need

to get down to business and begin investigating the issues raised in

the director’s memo.

6.

Direct students to the first question in the director’s memo.

Choosing from the available technologies, and using tissue sam-

ples from affected and unaffected individuals, how can they con-

firm the presence of disease at the cellular level in the affected

population?

If students ask what tissue samples are available, ask them to con-

sider which tissue samples they would want and why. Students

should reason that light microscopy can be used to look for the

presence of abnormal muscle cells in affected individuals. Unaf-

fected individuals should have normal muscle cells. Students

should provide a reason for wanting to look at any other tissue

samples.

84

7.

Ask students, “Why would you use light microscopy to confirm

the presence of disease?”

Students should know that cells are too small to be seen by the

naked eye, although they can be seen easily with a light micro-

scope. If necessary, ask students to think about the information on

Master 1.1, Searching for Scale (the size of a cell) and what they

discovered in Lesson 2, Activity 1: Probing for Answers (start with

the largest probe, in this case visible light).

8.

After deciding on a starting point (light microscopy), students

should begin to create their detailed research plan. Master 3.2,

Research Plan, presents an example of how a research plan can be

organized.

Either give each student a copy of Master 3.2 or make a transpar-

ency of Master 3.2 to show the class. It is important for students to

see how information flows as an investigation proceeds and how

what is done at one step depends on results from previous steps.

The research plan is constructed as a modified decision tree: if I see

(result 1), I will do (next task); or, if I see (result 2), I will do (next

task).

9.

Use the transparency of Master 3.2, Research Plan, to demon-

strate how the research plan is constructed. Use Master 3.3,

Example Research Plan, as your guide.

10. Begin by writing the question, Is there evidence of disease at the

cellular level (in muscle cells)?, in the space next to the state-

ment, “To answer the question.” Ask students to help you deter-

mine which technology to use to answer this question.

Students should begin their studies with light microscopy to look

for the presence of abnormal cells in the muscle tissue of affected

individuals. Write this response in the space next to the statement,

“I will use this technology.”

11. Ask students to respond to the statement, “I chose this technol-

ogy because.”

Students should reason that cells are too small to be seen with the

naked eye but can be seen easily using a light microscope. In other

words, the resolution of a light microscope is sufficient to see indi-

vidual cells. Record the response on the transparency.

12. Ask students to state a hypothesis.

There is (or is not) evidence of disease in muscle cells.

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13. Ask students what two results they would expect.

Either abnormal muscle cells will be seen in affected individuals or

they will not. Record this response on the transparency.

14. Ask students what question they would answer next if they

observe abnormal muscle cells in affected individuals.

Students would proceed to Question 2 on Master 3.1, Memo from

the Director, Is the disease caused by an infectious agent? Record

this response on the transparency.

15. Ask students what question they would answer next if they do

not observe abnormal muscle cells in affected individuals.

There is no single response to this question. Students can use their

imagination.

16. Inform students that they are ready to begin their studies. They

should create their research plans in a manner similar to that

demonstrated.

17. Inform the class that results indicate the presence of abnormal

muscle cells in tissue samples from affected individuals but not

in unaffected individuals. First, they will address the question of

whether or not the disease is caused by an infectious agent.

Students now begin working in smaller groups.

18. The Science Reference Manual lists two common pathogens: bacteria and viruses. How could they identify one or the other as a

potential cause of the disease (that is, as being present in affected

individuals and not present in unaffected individuals) using the

technologies available to them?

They should name the technology they would use, justify their

choice based on the size of the objects they are looking for and the

resolving power of the technology, and indicate possible results

and what their next step would be. Allow groups no more than five

minutes to formulate their plan.

19. Ask a group to present its research plan very briefly.

Students should focus on the 10- to 100-fold difference in size

between bacteria and viruses. Light microscopy can be used to

resolve bacteria but not viruses. Students should understand that

they are following a plan analogous to that developed in Lesson 2.

They start with the largest probe available (visible light) to find out

about the largest possible structures that can be resolved.

86

20. Ask whether any groups have a different research plan.

Ask groups with a different research plan to make a brief presentation.

Use class discussion to resolve differences or reinforce similarities.

21. Inform the class that light microscopy did not demonstrate the

presence of any structures resembling bacteria in tissue samples

from affected or unaffected individuals. On the basis of this

result, students should now formulate the next step in their

research plan.

As before, students should name the technology they would use,

Content Standard A:

justify their choice on the basis of the size of the objects they are

Formulate and revise

looking for and the resolving power of the technology, and indicate

scientific explanations

possible results and what their next step would be. Allow groups

and models.

two to three minutes to confirm their plan.

22. Ask a group to present its research plan very briefly.

Students should use transmission electron microscopy to see

whether viruses are present in any of the tissue samples. Viruses are

readily visible with this technique, which uses a probe (electrons)

that is smaller than the probe they used initially (visible light). Ask

students to justify any other approach they suggest.

23. Ask whether any groups have a different research plan.

Ask groups with a different research plan to make a brief presentation.

Use class discussion to resolve differences or reinforce similarities.

Part 2, How Does It Work?

1.

Inform the class of the following results:

• transmission electron microscopy demonstrated the pres-

ence of viruses in blood and muscle tissue samples from both

affected and unaffected individuals,

• no other tissue samples contained viruses,

• there were more viruses in muscle of affected people than in

unaffected people, and

• the viruses appeared to be associated with actin filaments in

the muscle.

2.

Ask students to consider these results as they develop their plan

to answer Questions 4 and 5 on the director’s memo (Master 3.1).

For instance,

• How do students interpret the presence of virus and the

absence of disease?

• How might this relate to how the virus produces disease in

susceptible individuals?

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echnology to Study What Your

Cellular Ear

and Hears

Molecular Biology

This may be a tough issue for students to deal with. It is not impor-

tant for them to come up with our scenario. It is important for

them to reason properly and use the available technologies to solve

whatever problem they perceive exists. They should consult their Sci-

ence Reference Manuals for helpful information.

A possible reasoned scenario is 1) virus is present in muscle tissue

of both affected and unaffected individuals because the virus binds

to a receptor in that tissue, 2) the virus nucleic acid codes for a

protein produced by the muscle cells, 3) the virus protein binds to

a key muscle protein in cells of affected individuals, which causes

the disease, 4) the virus protein does not bind to the muscle pro-

tein in cells of unaffected individuals, 5) the affected muscle protein

has a different structure from the unaffected protein, and 6) this

difference in structure allows the affected muscle protein to interact

with the virus protein.

3.

Ask groups to form a hypothesis based on their assessment of the

data presented in Step 1 of Part 2.

On the basis of the sample scenario presented in Part 2, Step 2,

one hypothesis might be as follows: the structure of the affected

muscle protein is different from that of the unaffected muscle pro-

tein. A related hypothesis might be that the virus protein binds to

the affected muscle protein and not the unaffected muscle protein

because of differences in structure between the two muscle pro-

teins. Another hypothesis is that the virus can attach to affected

muscle fibers and not to unaffected muscle fibers. There are many

possible hypotheses. It is important that each student hypothesis be

a testable statement that predicts a result.

4.

Ask groups to formulate a plan to test their hypothesis. They

should use only the techniques available to them.

On the basis of the sample scenario presented in Part 2, Step 2, stu-

dents might propose to do the following:

• use cryo-EM to generate a three-dimensional reconstruction

of the virus attached to the muscle to see whether the virus

attaches to affected muscle fibers and not unaffected muscle

fibers,

• use cryo-EM to produce three-dimensional reconstructions of

both the affected and unaffected muscle proteins to look for dif-

ferences in structure between the two,

• use X-ray crystallography to compare the structures of affected

and unaffected muscle proteins, or

• use either cryo-EM or X-ray crystallography to look at the struc-

ture of any virus-muscle protein combination that might form

(that is, a virus protein-affected muscle protein combination or a

virus protein-unaffected muscle protein combination).

88

Students might come up with other possibilities depending on the

hypothesis they formulate.

5.

Ask a group to present its hypothesis and research plan.

Content Standard A:

Members of each group should share the responsibilities of present-

Communicate and

ing the group’s information. Students should be encouraged to ques- defend a scientific tion the hypotheses and research plans developed by others. Remind argument.

students that science is a collaborative process in which scientists

must be able to support their ideas.

6.

Ask whether any groups have a different hypothesis or research

plan.

Ask groups with a different research plan to make a brief presenta-

tion. Use class discussion to resolve differences or reinforce similari-

Content Standard A:

ties. On the basis of feedback from their fellow scientists, groups

Recognize and analyze

should be allowed to revise their hypotheses and research plans.

alternative explana-

Part 3, What Can We Do about It?

tions and models.

1.

Thank students, on behalf of the Global Science and Health Orga-

nization, for their efforts so far. They must now think about devel-

oping a drug to treat this newly discovered disease.

2.

If the hypothesis students developed in Part 2 of this activity

(about how the virus might produce disease) is supported by exper-

imental data, how could students use a drug to treat the disease?

Even though students are still in groups, use this as an opportunity

for class discussion. Accept all responses. This question is inten-

tionally vague to stimulate student thinking. If students do not

understand the concept of drug targeting (that is, designing a drug

to interact specifically with another molecule, such as a host protein

or a molecule produced by a pathogen), direct them to review the

final item in Master 3.6, Science Reference Manual. The drug-specific

molecule can be one associated with the pathogen, such as a bacte-

rial or viral surface protein, or a protein produced by the pathogen.

Alternatively, the drug-specific molecule can be one associated with

the host, such as a receptor for the pathogen, or a molecule with

which a pathogen-produced substance interacts.

3.

Tell students that new data have been obtained. Provide each

group with a copy of Master 3.7, Muscle Protein Structures Deter-

mined by X-Ray Crystallography. Alternatively, use a transparency of this master for the class.

4.

Inform the class that the director of the Global Science and

Health Organization wants them to evaluate these structures with

89

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Molecular Biology

their fellow scientists (the other group members) and answer a

series of questions, which you will write on the board.

• How does the structure of the affected muscle protein compare

with the unaffected muscle protein? Are there differences?

The one difference between the two proteins is seen in the view

along the z-axis. The affected muscle protein has an opening

that is not present in the unaffected muscle protein.

• Do these results support a way that the virus could cause the

disease?

They could. It is possible that the affected muscle protein can

interact with the virus protein because its structure is different

from that of the unaffected muscle protein. Students might won-

der how this interaction could occur. They might speculate that

the virus protein interacts with parts of the affected muscle pro-

tein around the opening that exists. It may also be that the virus

protein interacts with some other region of the affected muscle

protein.

• On the basis of these results, what approach might be taken to

develop a drug to treat the disease?

This is another opportunity for students to relate structure to

function. They might reason that the affected muscle protein

interacts with the virus protein and not the unaffected muscle

protein because the two muscle proteins have different struc-

tures. This difference appears to be characterized primarily by

an opening in the affected muscle protein. Therefore, perhaps a

drug can be developed to change the affected muscle protein’s

structure to one more like the unaffected muscle protein. A

simple possibility is to develop a drug to close the opening.

Students may suggest other possibilities as well. Accept any

response that students can justify.

• Using the technologies available, how could potential drugs be

tested for effectiveness before using them to treat humans?

Responses will depend on the approach taken. For example, X-

ray crystallography would be an obvious choice for students who

want to demonstrate that a drug has returned the structure of the

affected muscle protein to that of the unaffected muscle protein.

Accept all responses as long as students justify their use.

5.

Allow groups 10 to 15 minutes to work on their responses. After

this time, reconvene the class and ask each group to present their

answers.

90

Part 4, This, Too, Is What Science Is All About

1.

Remind students that reporting their results is also an important

part of doing science. That is what they must do now.

Content Standard A:

2.

Instruct students to prepare a report that summarizes the work

Scientists conduct

done within their group.

investigations for a

wide variety of rea-

Students are to present all of their group’s work, from development

sons, such as to dis-

of a research plan to drug discovery. It is acceptable, based on class

cover new aspects

discussions and further reflection, to add their own touches to the

of the natural world,

group effort. Student reports should

to explain observed

• focus on justifying their choice of technology to solve specific

phenomena, or to

problems,

test conclusions of

• demonstrate an understanding of specimen size and resolution,

prior investigations or

and

predictions of current

• indicate a logical flow in which they use technologies of

theories.

increasing resolution to solve problems.

91

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How Y

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and Hears

Molecular Biology

Lesson 3 Organizer: Web Version

Activity 1: Putting Technology to Work

What the Teacher Does

Procedure Reference

Part 1, Solving the Problem

Divide the class into groups of two.

Pages 75–76

• Give each group a copy of Master 3.1, Memo from the

Steps 1–5

Director, Global Science and Health Organization.

• Ask students to read the memo.

• Explain that they will begin by formulating a research plan.

• Have students access the activity and click on the link to

the reference manual.

• Briefly review the contents of the reference manual.

Help students develop a research plan.

Pages 76–78

• Ask students how they would begin their studies.

Steps 6–16

• Guide students to the use of light microscopy to confirm

the presence of disease at the cellular level in affected

people.

• Give each student a copy of Master 3.2, Research Plan.

• Use a transparency of Master 3.2 to demonstrate how a

research plan is developed.

• With student input, fill in the required information on

the transparency. Use Master 3.3, Example of a Research

Plan, as a guide.

• In the space next to the statement, To answer the ques-

tion, write the question, Is there evidence of disease at

the cellular level (in muscle cells)? Ask students to help

you determine which technology to use to answer this

question.

• Ask students to respond to the statement, I chose this

technology because.

• Ask students to state a hypothesis.

• Ask students what two results they would expect.

• Ask students what question they would answer next if

they do not observe abnormal muscle cells in affected

individuals.

92

Instruct students to begin their studies. They should construct

Pages 78–79

their research plans in a manner similar to that demonstrated.

Steps 17–20

They should complete all tasks except the one dealing with drug

discovery (Question 6 on Master 3.1, Memo from the Director,

Global Science and Health Organization). Have groups share

their findings.

Part 2, Applying Technology . . . Again

Remind students of the final question to be answered: Is there

Page 81

a drug to treat or prevent the disease?

Step 1

Ask students,

Pages 81–82

• how the structural data on the affected and unaffected

Steps 2–3

muscle proteins, obtained by X-ray crystallography, sug-

gest a way that the virus could cause the disease and

• how a drug might be used to treat the disease.

Direct students to computers.

Page 82

• Tell students that they are to evaluate four new drugs

Steps 4–6

that are believed to have potential to treat the disease.

• Give each student a copy of Master 3.4, Drug Discovery

Evaluation Form, on which they should record their

observations and interpretations.

• Ask students to click on the link for the Drug Discovery

Laboratory on the unit’s desktop and complete the

activity.

Part 3, Wrapping It Up

Reconvene the class. Ask groups to share their drug evaluations.

Pages 82–83

• What were the drugs apparently designed to do?

Step 1

• Do any drugs show promise for treating the disease?

Instruct students to prepare a report that summarizes their

Page 83

work.

Step 2

= Involves copying

= Involves using

= Involves using

a master.

a transparency.

the Internet.

93

Student

Student L

L essons

esson 3

How Y

Usingour

T Brain Understands

echnology to

What

Study

Your

Cellular Ear

and Hears

Molecular Biology

Lesson 3 Organizer: Print Version

Activity 1: Putting Technology to Work

What the Teacher Does

Procedure Reference

Part 1, What Is It?

Divide the class into groups of three or four.

Pages 83–84

• Give each group a copy of Master 3.1, Memo from the

Steps 1–4

Director, Global Science and Health Organization.

• Ask students to read the memo.

• Show students the transparency of Master 3.5, Available

Technologies.

• Give each group a copy of Master 3.6, Science Reference

Manual.

Ask students how they will begin their studies. Direct attention

Pages 84–85

to the first question on the director’s memo. Ask,

Steps 5–7

• “Choosing from the available technologies and using tis-

sue samples from affected and unaffected individuals,

how can you confirm the presence of disease at the cel-

lular level in the affected population?”

• “Why would you use light microscopy to confirm the

presence of disease?”

After deciding on a starting point, students should begin con-

Pages 85–86

structing their research plan.

Steps 8–16

• Use the transparency of Master 3.2, Research Plan, to

demonstrate how the research plan is constructed.

• With student input, fill in the required information on

the transparency. Use Master 3.3, Example of a Research

Plan, as a guide.

• In the space next to the statement, To answer the ques-

tion, write the question, Is there evidence of disease at

the cellular level (in muscle cells)? Ask students to help

you determine which technology to use to answer this

question.

• Ask students to respond to the statement, I chose this

technology because.

• Ask students to state a hypothesis.

• Ask students what two results they would expect.

• Ask students what question they would next answer if

they do not observe abnormal muscle cells in affected

individuals.

94

Inform the class that results indicate the presence of abnormal

Pages 86–87

muscle cells in tissue samples from affected individuals but not

Steps 17–20

in unaffected individuals.

• The class will first address the question of whether or

not the disease is caused by an infectious agent.

• Their science reference manual lists two common patho-

gens: bacteria and viruses.

• Ask students how they could identify one or the other as

a potential cause of the disease using the technologies

available to them.

• Ask a group to present its research plan.

• Ask if any groups have a different research plan.

Inform the class that light microscopy did not demonstrate the

Page 87

presence of any structures resembling bacteria in tissue samples

Steps 21–23

from affected or unaffected individuals.

• On the basis of this result, students should now formu-

late the next step in their research plan.

• Ask a group to present its research plan.

• Ask whether any groups have a different research plan.

Part 2, How Does It Work?

Inform the class of the following results:

Page 87

• transmission electron microscopy demonstrated the

Step 1

presence of viruses in blood and muscle tissue samples

from both affected and unaffected individuals;

• no other tissue samples contained viruses;

• there were more viruses in muscle of affected people

than in unaffected people; and

• the viruses appeared to be associated with actin

filaments in the muscle.

Ask students to consider these results as they develop their

Pages 87–88

plan to answer Questions 4 and 5 on the director’s memo. For

Step 2

instance,

• how do students interpret the presence of virus and the

absence of disease, and

• how might this relate to how the virus produces disease

in susceptible individuals?

Ask groups

Pages 88–89

• to form a hypothesis based on their assessment of the

Steps 3–4

data presented in Step 1, Part 2, and

• to formulate a plan to test their hypothesis.

95

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Molecular Biology

Ask a group to present its hypothesis and research plan.

Page 89

Step 5

Ask if any groups have a different hypothesis or research plan.

Page 89

Step 6

Part 3, What Can We Do About It?

Inform the class that they must now think about developing a

Page 89

drug to treat the disease.

Step 1

On the basis of the hypotheses they developed in Part 2, how

Page 89

might students use a drug to treat the disease?

Step 2

Tell students that new data have been obtained. Give each

Page 89

group a copy of Master 3.7, Muscle Protein Structures Deter-

Step 3

mined by X-Ray Crystallography, or use a transparency for the

class.

Inform the class that they are to evaluate these structures and

Pages 89–90

answer a series of questions, which you write on the board.

Step 4

• How does the structure of the affected muscle protein

compare with the unaffected muscle protein?

• Do these results support a way that the virus could

cause the disease?

• What approach might be taken to develop a drug to

treat the disease?

• Using the technologies available, how could potential

drugs be tested for effectiveness before using them to

treat

humans?

Allow groups 10 to 15 minutes to work on their responses.

Page 90

Reconvene the class and ask each group to present their

Step 5

answers.

Part 4, This, Too, Is What Science Is All About

Remind students that reporting their results is also a part of

Page 91

doing science.

Step 1

Instruct students to prepare a report that summarizes the work

Page 91

done within their group.

Step 2

= Involves copying a master.

= Involves using a transparency.

96

Lesson 4

Evaluate

Technology: How Much

Is Enough?

Overview

At a Glance

This lesson gives students an opportunity to pull information together

and demonstrate an understanding of the basic concepts discovered in

earlier lessons. In the first of two activities, students use the scenario

from Lesson 3 to evaluate technology from a historical perspective. They

first develop timelines for key developments in biology, medicine, and

technology. They then are asked, If you were a scientist in the mid-1800s,

how much progress would you make in solving the problems in Lesson

3? In the second activity, students consider whether our technology tool-

box is complete. They choose one of three problems and propose a tech-

nology or combination of technologies to solve it.

Major Concepts

New technologies are developed, and old technologies are improved and

refined, continuously. This must be done to meet the demands created by

new and existing problems.

Objectives

After completing this lesson, students will

• be able to describe the need for new or improved technologies;

• be able to explain the general process of developing technologies,

including the need to have input from multiple disciplines.

Teacher Background

See the following sections in Information about Using Technology to

Study Cellular and Molecular Biology:

4 Major Techniques in the Study of Cellular and Molecular Biology

(pages 26–35)

5 Technology and the Origins of Molecular Biology (pages 35–38)

97

Using Technology to Study Cellular and Molecular Biology

In Advance

Web-Based Activities

Activity

Web Version

1

No

2

No

Photocopies

Activity 1

• Master 4.1, Microscopes Across Time, 1 transparency

• Master 4.2, Some Key Developments in Biology, Medicine,

and Technology, 1 transparency

Activity 2

none required

Materials

Activity 1 • 24 sheets of white copying paper

• black marker

• blank transparency; or a string as long as the width of

classroom, 29 paper clips, and 5 sheets of white copying

paper

Activity 2

none required

Preparation

Activity 1

On each of 24 sheets of white paper, use the black marker to write one

of the key developments listed on Master 4.2, Some Key Developments in

Biology, Medicine, and Technology (eight developments are listed in each

of three categories: biology, medicine, and technology). Do not provide

the year of the development or the name(s) of the individual(s) involved.

There are two options for this activity: use a blank transparency to record

student responses as they construct the timeline for developments in

biology, medicine, and technology, or stretch the string across the width

of the classroom and affix it well at both ends. If you choose the second

option, write one of the following on each of five sheets of white paper:

1600, 1700, 1800, 1900, or 2000. Use a paper clip to attach the sheet

indicating 1600 at the near the left end of the string. Attach the sheet

indicating 2000 near the right end of the string. Attach the remaining

sheets with 1700, 1800, and 1900 in order between 1600 and 2000.

Activity 2

No preparations needed.

98

Activity 1: Time Travel

Procedure

1.

Show students the transparency of Master 4.1, Microscopes Across

Time. Ask them to look at the pictures of the microscopes and

describe the differences they observe.

Write student responses on the board. The pictures present micro-

scopes developed over approximately 250 years. Students can

respond to differences in design, such as the development of mul-

tiple objective lenses. Some students may respond with differences

that are implied, such as better optics, electrical components, and

computerized components. The objective of this question is to

engage student thinking about the changing face of science and

technology across time.

2.

Ask the class to imagine that they are scientists or physicians

living in the mid-1800s. How much progress do they think they

would make solving the problems in Lesson 3?

For example, could they have identified the infectious agent?

Could they have determined how the disease was caused? Students

will probably have little specific knowledge of when relevant dis-

coveries were made or when relevant technologies were developed.

Allow the students to wonder about the timeline of scientific dis-

covery. Even though the problems in Lesson 3 are the same as in

any time period, the technologies and knowledge available at a

given time will determine the extent to which the problems can be

solved.

3.

Divide the class into three groups.

One group will focus on biology, the second on medicine, and the

third on technology.

4.

Provide each student in the biology group with one sheet on

which a biology development is written. Provide each member of

the medicine and technology groups with one sheet on which a

Content Standard E:

development appropriate to their group is written.

Science often

advances with new

In classes with fewer than 24 students, you can give students more

technologies.

than one sheet or you can give the group all eight sheets. In classes

with more than 24 students, you can add the following develop-

ments:

• biology: covalent bond described (1916, Gilbert Lewis), gene-

sequencing methods developed (1977, Walter Gilbert and Allan

Maxam, and Fred Sanger and Alan Coulson);

99

Student Lesson 4

Using Technology to Study Cellular and Molecular Biology

• medicine: first vaccination (1796, Edward Jenner), aspi-

rin introduced (1899, Felix Hoffmann);

• technology: protocol allowing different computer net-

works to interconnect and communicate with each

other (1973, Vinton Cerf and Bob Kahn), automated

DNA sequencer introduced (1986, Leroy Hood and col-

leagues).

Other developments can be added at the teacher’s discretion.

5.

Ask students to estimate the year the development on their

sheet occurred.

6.

Ask students to consult with other group members to place

all developments in their category in chronological order.

Allow only a few minutes for students to do this.

7.

Have students report their results.

This can be accomplished two ways. Students can call out

their results to the teacher, who then records the informa-

tion along a line drawn on a blank transparency projected for

the class to see. Alternatively, students can clip their sheets

to the string that spans the width of the room. Sheets should

be placed at a location representing the approximate date of

each development. For instance, a development occurring in

1850 would be placed midway between 1800 and 1900.

8.

Show students a transparency of Master 4.2, Some Key

Developments in Biology, Medicine, and Technology, and

quickly evaluate how students did at constructing their

timeline.

9.

Looking at the timeline, ask students what progress they

could have made in solving the problems in Lesson 3 if

they were working in the mid-1800s.

Students see that technologies available in 1850 were not

capable of providing the information required to solve the

problems in Lesson 3. Students also develop a firmer under-

standing of the relationship between technology development

and the advancement of knowledge.

Activity 2: Is That All There Is?

Teacher note: This activity should follow Activity 1 without a

break in discussion.

100

1.

Ask students if our present technology toolbox is complete. With

a show of hands, how many students believe we need new tech-

nologies?

You might ask students to suggest some new technologies and write

these suggestions on the board. Student responses are less impor-

Content Standard E:

tant than shifting the focus from existing technologies to new ones

Many scientific investi-

(or refinements of existing ones).

gations require contri-

butions from different

2.

Tell students that they will accelerate their journey through time.

disciplines, including

They are now scientists in the year 2052. Since students know

engineering.

that technologies are generally developed by teams whose mem-

bers have expertise in more than one discipline, they now will

Content Standard E:

work in teams.

Creativity, imagination,

and a good knowledge

3.

Divide the class into groups of four or five. Ask each group to

base are all required

choose one of the following problems:

in the work of science

• development of a technology to detect and measure concen-

and engineering.

trations of the abnormal protein in affected people from Les-

son 3 (that is, a biosensor),

• development of a technology to determine the structure of a

protein molecule without having to prepare a crystal of the

protein, or

• development of a technology that allows molecules of a drug

to be delivered specifically to the protein of affected people

from Lesson 3 in a way that allows the physician or scientist

to know how much drug is delivered.

4.

Instruct students to work with their group members to outline

the requirements of their technology.

This is a challenging activity for students. However, the key issue is

the rationale students provide for their technology. Students should

consider at least the following:

Content Standard G:

• What disciplines are involved in developing the technology?

Scientific explanations

• Is it a new technology or a refinement of an existing technology?

must meet certain

• What is the level of resolution required?

criteria such as consis-

• How are the issues of scale and probe size dealt with?

tency and accuracy.

• In general terms, how does the technology work?

5.

Reconvene the class. Each group in turn should present its tech-

nology.

Use class discussion to discover problems and weaknesses and to

help group members refine their ideas.

101

Student Lesson 4

Using Technology to Study Cellular and Molecular Biology

6.

As a final means of assessment, ask each student to prepare a

written report describing his or her technology.

Technologies should be described in sufficient detail to indicate the

student’s understanding of the concepts presented in this module.

102

Activity

Lesson 4 Organizer

Activity 1: Time Travel

What the Teacher Does

Procedure Reference

Show students a transparency of Master 4.1, Microscopes Across Page 99

Time. Ask them to look at the microscopes and describe the dif-

Step 1

ferences they observe.

Ask the class to imagine that they are scientists or physicians

Page 99

living in the mid-1800s. How much progress do they think they

Step 2

would make solving the problems in Lesson 3?

Divide the class into three groups.

Pages 99–100

• One group will focus on biology, the second on medi-

Steps 3–7

cine, and the third on technology.

• Provide each student with a sheet of paper on which is

written one development in his or her focus area.

• Ask students to estimate the year the development on

their sheet occurred.

• Ask students to consult with other group members to

place all developments in their focus area in chronologi-

cal order.

• Have students report their results.

Show students a transparency of Master 4.2, S ome Key Develop- Page 100

ments in Biology.

Steps 8–9

• Evaluate how students did at constructing their timeline.

• Ask students what progress they could have made in

solving the problems in Lesson 3 if they were working in

the mid-1800s.

Activity 2: Is That All There Is?

Ask students,

Page 101

• “Is our present technology toolbox complete?”

Step 1

• “How many students believe we need new technologies?”

103

Student Lesson 4

Using Technology to Study Cellular and Molecular Biology

Divide the class into groups of four or five.

Page 101

• Tell students they are scientists in the year 2052.

Steps 2–4

• Ask each group to choose one of the following prob-

lems:

o development of a technology to detect and mea-

sure concentrations of the abnormal protein in

affected people from Lesson 3;

o development of a technology to determine the

structure of a protein molecule without having to

prepare a crystal of the protein; or

o development of a technology that allows mol-

ecules of a drug to be delivered specifically to

the protein of affected people from Lesson 3 in a

way that allows the physician or scientist to know

how much drug is delivered.

• Instruct students to work with their group members to

outline the requirements of their technology, focusing on

concepts learned in earlier lessons.

Reconvene the class and allow each group to present its

Page 101

technology.

Step 5

As a final assessment, ask each student to prepare a written

Page 102

report describing his or her technology.

Step 6

= Involves using a transparency.

104

Lesson 1

Engage

title

Masters

Lesson 1, What Is Technology?

At a Glance

Master 1.1, Searching for Scale

1

copy

per

student

Lesson 2, Resolving Issues

Master 2.1, Probing for Answers Score Sheet

1

copy

per

2

students,

1

transparency

Master 2.2, Probes

1

copy

per

12

students

Masters 2.3 to 2.8, Probing for Answers—Levels 1–6

1 copy of each per 12

or

fewer

students;

2

copies

of

each

for

13–24

students;

3

copies

of

each

for

25–36

students

Master 2.9, Solution to Probing for Answers

1

transparency

( print version only)

Lesson 3, Putting Technology to Work

Master 3.1, Memo from the Director, Global Science

and Health Organization

1

copy

per

group

Master 3.2, Research Plan

1

copy

per

student,

1

transparency

Master 3.3, Example of a Research Plan 1

transparency

Master 3.4, Drug Discovery Evaluation Form

1

copy

per

student

( Web version only)

Master 3.5, Available Technologies

1

transparency

( print version only)

Master 3.6, Science Reference Manual

1

copy

per

group

( print version only)

Master 3.7, Muscle Protein Structures Determined by

X-Ray Crystallography

1

copy

per

group

or

1

transparency

( print version only)

Lesson 4, Technology: How Much Is Enough?

Master 4.1, Microscopes Across Time

1

transparency

Master 4.2, Some Key Developments in Biology,

Medicine, and Technology

1

transparency

105

Searching for Scale

Name:

Date:

Biological

Actual

Size Relative to Cell Object Used to

Measured

Size Relative

Structure

Diameter

Model Biologi-

Size of

to Model Cell

(in Meters)

cal structure

Model Object

(the Room)

Cell

1 × 10–5

1 × 10–5

Room

10 meters

10

= 1

= 1

1 × 10–5

10

Bacterium

1 × 10–6

1 × 10–6

Desk

1 meter

= 1

1 = 1

1 × 10–5 10

10 10

Mitochondrion

5 × 10–7

5 × 10–7 = 1

1 × 10–5 20

Virus

1 × 10–7

Ribosome

1 × 10–8

Protein

5 × 10–9

Glucose

1 × 10–9

molecule

H2O molecule

1 × 10–10

Master 1.1

Probing for Answers Score Sheet

A

B

C

D

E

F

G

H

I

1

2

3

4

5

6

7

8

9

Master 2.1

Probes

Master 2.2

Probing for Answers—Level 1

A

B

C

D

E

F

G

H

I

1

2

3

4

5

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7

8

9

Level 1

Master 2.3

Probing for Answers—Level 2

A

B

C

D

E

F

G

H

I

1

2

3

4

5

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7

8

9

Level 2

Master 2.4

Probing for Answers—Level 3

A

B

C

D

E

F

G

H

I

1

2

3

4

5

6

7

8

9

Level 3

Master 2.5

Probing for Answers—Level 4

A

B

C

D

E

F

G

H

I

1

2

3

4

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8

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Level 4

Master 2.6

Probing for Answers—Level 5

A

B

C

D

E

F

G

H

I

1

2

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6

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Level 5

Master 2.7

Probing for Answers—Level 6

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B

C

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Level 6

Master 2.8

Solution to Probing for Answers

Master 2.9

Memo from the Director, Global Science and

Health Organization

Global Science and

Health Organization

Memo

TO:

Members, Scientific and Health Evaluation Teams

FROM:

Director, Global Science and Health Organization

RE:

New disease

Our Division of Disease Surveillance recently reported a new disease affecting approximately 30% of the persons living in a small rural area of the United States. Affected individuals have a lack of energy and demonstrate a progressive loss of muscle function. Although we have no information yet, we believe the disease is caused by an infectious agent. Consequently, to limit the spread of this disease, immediate intervention is critical.

We need your expertise to answer these questions:

1.

Is there evidence of disease at the cellular level? If so,

2.

Is the disease caused by an infectious agent? If it is,

3.

What is the infectious agent?

4.

Does the infectious agent attack muscle tissue?

5.

How might the infectious agent cause the disease?

6.

Is there a drug to treat or prevent the disease?

Blood and muscle tissue samples from unaffected and affected individuals are waiting for you. The microscopy and X-ray crystallography facilities at GSHO are being readied for your arrival. In order to gain information as quickly as possible, please develop a solid research plan before beginning your investigations.

Good luck!

Master 3.1

Research Plan

Name:

Date:

1.

To answer the question,

2.

I will use this technology:

3.

I chose this technology because

4.

My hypothesis is

5.

I expect one of the following two results:

6.

Observations (actual results) and interpretation:

Master 3.2

Example of a Research Plan

1.

To answer the question, Is there evidence of disease at the cellular level (in

muscle cells)?

2.

I will use this technology: Light Microscope

3.

I chose this technology because its resolution level allows me to see muscle cells.

4.

My hypothesis is There is evidence of disease in muscle cells.

5.

I expect one of the following two results: I will see abnormal muscle cells in affected individuals OR I will see NO abnormal muscle cells in affected individuals.

6.

Observations (actual results) and interpretation:

Result 1—Muscle cells from affected individuals are different from normal muscle

cells and those from unaffected individuals; interpreted as evidence of disease in

muscle of affected individuals. Proceed to next question.

1.

To answer the question, Is the disease caused by an infectious agent (bacteria)?

2.

I will use this technology: Light Microscope

3.

I chose this technology because its resolution level allows me to see bacteria.

4.

My hypothesis is (continue as above).

OR

6.

Observations (actual results) and interpretation:

Result 2—Muscle cel s from affected individuals appear the same as normal muscle cel s and muscle cel s from unaffected individuals. Interpreted as lack of evidence of disease in muscle cel s of affected individuals. Look for evidence of disease in other tissues.

1.

To answer the question, Is there evidence of disease at the cellular level (blood)?

2.

I will use this technology: Light Microscope

3.

I chose this technology because its resolution level allows me to see blood cells.

4.

My hypothesis is (continue as above).

Master 3.3

Drug Discovery Evaluation Form

Name:

Date:

Molecule 1: Evaluation of X-ray crystallography, protein structure data:

Molecule 2: Evaluation of X-ray crystallography, protein structure data:

Molecule 3: Evaluation of X-ray crystallography, protein structure data:

Molecule 4: Evaluation of X-ray crystallography, protein structure data:

Overall evaluation: Is there a drug you would recommend to treat the disease? Justify your response.

Master 3.4

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Master 3.5

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Science Reference Manual

Section 3: Blood

Section 4: Muscle

Muscle Structur

Muscle Pr

Muscle Contraction

Section 5: Drug Discovery

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Section 1: T

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Section 2: Infectious

Disease Causative Agents

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Muscle Structure

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fibers, each of which extends the length of the muscle (up to 2.5 feet long).

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Science Reference Manual

a light micr

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Master

get cellular

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om

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Rational Basis for New Drug Development

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Cr

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two thin actin filaments (right).

The key to rational drug design is understanding the structur

biological molecules involved in disease development. T

disease, scientists sear

and molecular factors that play a r

drug design, including micr

analyses, and simulations.

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Science Reference Manual

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Muscle Proteins

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Muscle Contraction

es actin, myosin, and other pr

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equir

e made up of many dif

e twisted into a double helix to form an actin filament.

. Their arrangement and individual pr

oteins stabilize the filament.

ectly involved in muscle contraction and r

e dir

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a specific way

muscle to function. Some pr

ar

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thin filaments of the cells.

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these chains ar

Specialized pr

At the tip of the myosin molecule is a cleft that binds to the actin filament. The

lever arm of the myosin pushes the myosin molecule along the actin filament.

Muscle contraction r

mineral calcium, and ener

Master

Muscle Protein Structures Determined by

X-Ray Crystallography

Muscle protein from affected people

Along z-axis

Along x-axis

Along y-axis

Muscle protein from unaffected people

Along z-axis

Along x-axis

Along y-axis

Master

Master 3.7

Microscopes Across Time

1754

1850

1909

Culpepper microscope

Ross microscope

Leitz Wetzler microscope

1948

2004

Spencer microscope

Modern research microscope

Master

Master 4.1

Some Key Developments in Biology,

Medicine, and Technology, by Year

BIOLOGY

1665

Cells first described (Robert Hooke).

1839

Proposal made that animal tissues are composed of cells (Theodor Schwann).

1869

DNA discovered (Friedrich Miescher).

1911

Structure of the atom discovered (Ernest Rutherford).

1942

Myosin and actin reported to be the main structural proteins of muscle (Albert Szent-Gyorgi and colleagues).

1953

Double helix model of DNA proposed (James Watson and Francis Crick; their model was supported by X-ray crystallography done by Maurice Wilkins and Rosalind Franklin).

1953

Structure of hemoglobin determined using X-ray crystallography (Max Perutz and John Kendrew).

2000

Atomic structure of the large subunit of a bacterial ribosome resolved using X-ray crystallography (Thomas Steitz and colleagues).

MEDICINE

1862

Germ theory published: infection is caused by bacteria (Louis Pasteur).

1868

First diagnosis made of a complex disease, multiple sclerosis (Jean Martin Charcot).

1892

Viruses discovered (Dimitri Ivanovsky).

1892

White blood cells identified (Elie Metchnikoff).

1893

First modern American medical school opens (Johns Hopkins University, Baltimore, Md.).

1895

First pharmaceutical research laboratory founded (Parke-Davis Company, Detroit, Mich.).

1928

Penicillin discovered (Alexander Fleming).

1959

First major drug to treat leukemia invented (Gertrude Elion).

TECHNOLOGY

1593

Thermometer invented (Galileo).

1883

First induction motor constructed, the basis of generating electricity (Nicola Tesla).

1895

X-rays discovered (Wilhelm Conrad Roentgen).

1912

X-ray crystallography invented (William Bragg).

1923

First electric refrigerator produced (Electrolux, Old Greenwich, Conn.).

1927

First working model of television (Philo Farnsworth).

1932

Electron microscope invented (Max Knoll and Ernst Ruska).

1969

First microprocessor designed, the basis for computer development (Marcian Hoff).

Master

Master 4.2

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