Moving Evolution Education Forward

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Moving Evolution Education Forward: Why Evolution

and Evolutionary Thinking are Integral Components of

Molecular Biology of the Cell

NRC/NAS Convocation on Thinking Evolutionarily: EvolutionEducation Across the Life Sciences

October 26, 2011

Bruce Alberts,

University of California, San Francisco (UCSF)Editor-in-Chief, Science magazine


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Watson Roberts Raff Lewis Bray Alberts

Writing a textbook for 33 years : the first set of authors


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The joy of textbook writing


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Learning from writing for teaching:

The authors have all learned a great dealfrom 30 years of writing this large textbook


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From the preface of our 4th edition:

We are no longer as confident as we were

18 years ago that simplicity will emergefrom the complexity. The extremesophistication of cellular mechanisms willchallenge cell biologists throughout thenew century, which is very good news forthe many young scientists who willsucceed us.

In the process of writing, we all learneda great deal about the cell


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How I and my fellow students viewed

the cell in 1960As chemists, we were impressed by the enormouscollision rate of molecules. For example, the active site on anenzyme that binds a substrate molecule present at 0.5mM will experience

500,000 random collisions with that substrate per second, even though

there is only one substrate molecule for every 100,000 water molecules.

We therefore thought of the cell as a tiny test tube,

composed of an enormously concentrated mixture of individualmacromolecules that were freely diffusing and colliding

randomly.


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The cell is nothing

like a test tube!


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One example: intracellular

compartmentation without membranes


10/59Figure 16-38 Molecular Biology of the Cell( Garland Science 2008)

A simple

example: the

whiskers on theredprotein here

(called formin)

allow the actin

filaments in cellsto grow at rates

faster than

diffusion

controlled

(from T. Pollard et al)


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What life is really like:

A cartoon from a 2011 review


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My conclusion: The chemistry in cells is enormouslysophisticated, and it will probably take most of this

century to gain a true understanding of how cells andorganisms work

Because ofevolution, the shortest path for workingout the mechanisms in human cells will often startwith molecular studies in simpler model organisms !


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I can give you a personal example


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I was a highschool student,

when therevolution inbiology began withthe Watson and

Crick structure forDNA in 1953

Watson

Crick


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The Watson-Crick model for information transfer: DNA

templating through complementary base pairs

A problem for the DNA replication mechanism: the two DNAstrands run in opposite chemical directions


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1) The DNA polymerase enzyme was discoveredby Arthur Kornberg and earned him a Nobel

Prize.

2) This protein will add a new nucleotide to the endof one DNA strand (the primer strand) only ifthat strand is paired to a complementary strand

that can serve as the template (the templatestrand).

The next major breakthrough: the discovery of

the enzyme that synthesizes DNA


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The DNA polymerase in action


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3

5

template strand

DNA polymerase addsone nucleotide and then

dissociates

A second DNApolymerase molecule

adds the next nucleotide

primer strand

3

5

How we viewed DNA replication in the 1960s


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My dismal career as a graduate

student, Harvard 1961-1965

Can we get the DNA double helix toreplicate in a test tube?

I did many experiments trying to see howthis might happen using only the DNA

polymerase enzyme. They all failed.


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When I moved to Geneva Switzerland as apost-doctoral fellow in 1965, I discovered

that DNA replication must require muchmore than the DNA polymerase


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Bacteriophage T4, a large bacterial virus, had about

100 genes discovered by genetics by 1965


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A major mystery in 1965: why were there atleast 7 T4 genes that were absolutelyrequired for replication of the T4 virus?

1) These 7 T4 genes had been given numbers: 32, 41,43, 44, 45, 61, 62.

2) One of these, the gene 43, had been shown toproduce the T4 bacteriophage DNA polymerase.

3) Why are at least 6 additional proteins needed forany replication of the T4 chromosome when thevirus infects the E. coli bacterium?

4) Clearly, DNA replication must involve at least 7proteins and be much more complicated than

anyone had imagined!


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Result of 20 years of research at Princetonand UCSF

A protein machine


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The magic of protein machines is best

appreciated by a movie that shows such amachine in action.

The movie was made by Bruce Stillman at theCold Spring Harbor Laboratory, as part of the50 year DNA celebration there. Download byGoogling:YouTube Garland Science DNA.


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We now know that the same basic mechanismis used to replicate DNA from large viruses,

like T4 bacteriophage, to mammals

However, as more complex organismsevolved, each function in T4 was carried outby more proteins

For example, bacteria use 13 proteinmolecules instead of 7, and humans use about40!


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Two lessons learned in the last 20 years

1) Because of evolution, there are remarkablehomologies between living things; therefore usemodel organisms wherever possible.

2) Nearly all cell processes will be:

driven by 10 to 20 proteins, organized as a proteinmachine and incorporating ordered protein movements

driven by the energy of ATP hydrolysis

based on elegant mechanisms that are too complex topredict.


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1) Obtaining the information needed to

accurately describe the mechanism of every type

of protein machine in a cell.

This will require the reconstitution of manyhundreds of protein machines from their purified

components, so that their detailed chemistry can

be deciphered through reactions studied in a testtube.

Then, we will also need to work out the manyinteractions between different protein machines

An Important Challenge for the Next

Generation of Cell Biologists


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A cell is the fundamental unit of life

What underlies its chemistry?


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food in

waste out


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Bacterial

cells on thetip of a pin

Todays cells are very complex!


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Today s cells are very complex!


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2). Completing our understanding of one typeof cell.

It is not enough to have a catalogue of allthe pieces. We must also be able to explainhow these pieces all add up to make aliving thing.

For this purpose, many laboratories willneed to focus on the same,

simple

cell(for example, Mycoplasma, a tiny bacterium

with only 500 genes compared to the 25,000genes of humans).

A Second Important Challenge for the Next

Generation of Biologists


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The simplestliving cell

known, a tiny

bacteriumcalled

Mycoplasma

Dividingcell, aboutto producetwo cellsfrom one


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Why did multicellular

organisms evolve on theearth?

Multicellularity permits cell specialization, with cells indifferent places having different functions for theorganism as a whole.

Consider a plant: the advantages include being ableto have root cells deep underground to absorb waterand leaf cells in the sun to carry out photosynthesis.


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Many cells must cooperate to form amulticellular organism: but cooperation

is very difficult!

Single-celled life was all there was on the earth forabout 2 billion years.

Finally, about 1.5 billion years ago, the first cellslearned how to form cooperatives and larger and

larger organisms began to evolve.


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A simple multicellular organism:

a cell cooperative


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More complicated


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Much more complicated


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A very complex multicellular organism!

Thousands ofbillions of cells

A Thi d I t t Ch ll f th N t


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3). Understanding how cells make decisions in acomplex multicellular organism like ourselves.

Cells constantlytalk

to each other. Then eachcell integrates what it is hearing to control its

behavior for the good of the entire assembly ofcells that makes up the organism.

We need to understand this complex process ofcell thinking.

A Third Important Challenge for the Next


Signals coming


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Cell signaling

Decision

network inone cell

Signals comingfrom other cells

A F th I t t Ch ll f th N t


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4). Using our increasingly profound understandingof molecular cell biology to design intelligent

strategies for improving human health.

For example, rare aberrant cells give rise to theuncontrolled cell proliferation know as cancer.

Once we truly understand how cells think, we canmake these cells commit suicide withoutaffecting the other, normal cells of the body.

A Fourth Important Challenge for the Next


A Fifth I t t Ch ll f th N t


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5). Deciphering the complicated pathways by

which cells and organisms evolved on the

Earth.

Some powerful tools: comparative genomics,

biochemistry, chemistry.

A Fifth Important Challenge for the Next

Generation of Cell Biologists

L i


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Learningfrom

evolution:A comparison

of genomesequences

fromMolecular

Biology of the

Cell

Wh d f ?


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Where do we come from?

John A Moore and the Science as a Way of Knowing


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John A. Moore and the Science as a Way of Knowing(SAAWOK) Cell Biology crowd in 1989


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JohnsScienceasaWayofKnowingseriesis

availableatwww.SICB.org/dl/saawok.php3

Evolu=onaryBiology.1984.Amer.Zool.24:421-534.HumanEcology.1985.Amer.Zool.25:377637.

Gene=cs.1986.Amer.Zool.26:773-914.

DevelopmentalBiology.1987.Amer.Zool.27:415732.

FormandFunc=on.1988.Amer.Zool.28:443738.

CellandMolecularBiology.1989.Amer.Zool.29:483812

NeurobiologyandBehavior.1990.Amer.Zool.30:403858.

PLUS

AConceptualFrameworkforBiologyPartsI,II,andIII.Amer.Zool.1989,1990,and1991(These3total300pages!)

The chapter that I co-wrote with John


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ThechapterthatIco wrotewithJohn(fromtheAcademysTeachingaboutEvolu1onandthe

NatureofScience,1998)


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The challenge of scienceeducation

Two (sad) true stories:

1). A third grader returning from school, speaking to

his scientist mother: Now I understand science. Itis the same as spelling: you just have tomemorize it because it does not make any sense.


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The challenge of scienceeducation

Two (sad) true stories:

2). From Focus Groups of college-educated adults

convened on behalf of the National Academy ofSciences: Science is what scientists believe;religion is what religious leaders believe. Both areequivalent, dogmatic belief systems and (with

respect to evolution) I can chose either one.


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UsingScience

magazine to

create more

coherence inthe field of

education


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As Jay Labov emphasized this morning,how we teach our introductory college

science classes is the key to anyredefinition of science education!!


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1). Work with other scientific societies toreshape college introductory biology courses

so that they address all 4 strands of science

proficiency in the National Academies TakingScience to School.

E.g., emphasize the importance of high-quality, low-resource

lab modules that stress student inquiry, to replace thestandard follow-the-instructions, cooking college laboratories.

Whatscien=ficsocie=escando

2011 contest for best inquiry lab modules for


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2011 contest for best inquiry lab modules for

introductory college science


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2). Work with other scientific societies to

increase the importance and prestigeassociated with being a great teacher of

science, at all levels.

Remember that Focus Groups suggest that a failureto understand the nature of science (John A. Moores

science as a way of knowing) lies at the heart of the

evolution versus creationism debate in the US.

Our teaching of college science as therevealed truth from scientists has not worked!

Interactive no lecture science classroom


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Interactive, no lecture science classroom

University of Minnesota (Professor Robin Wright)

(22 tables, each with 9 chairs, two computers, overhead screen)


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Documents

Moving Evolution Education Forward