Moving Evolution Education Forward: Why Evolution and Evolutionary Thinking are Integral Components of Molecular Biology of the

Cell
NRC/NAS Convocation on Thinking Evolutionarily: Evolution Education Across the Life Sciences October 26, 2011 Bruce Alberts, University of California, San Francisco (UCSF) Editor-in-Chief, Science magazine

Watson

Roberts

Raff

Lewis

Bray

Alberts

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

The joy of textbook writing

Learning from writing for teaching:

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

5th edition in Antarctica 2008

In the process of writing, we all learned a great deal about the cell
From the preface of our 4th edition: We are no longer as confident as we were 18 years ago that simplicity will emerge from the complexity. The extreme sophistication of cellular mechanisms will challenge cell biologists throughout the new century, which is very good news for the many young scientists who will succeed us.

How I and my fellow students viewed the cell in 1960

As chemists, we were impressed by the enormous collision rate of molecules. For example, the active site on an
enzyme 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 individual macromolecules that were freely diffusing and colliding randomly.

The cell is nothing like a test tube!

One example: intracellular compartmentation without membranes

A simple example: the whiskers on the red protein here (called formin) allow the actin filaments in cells to grow at rates faster than diffusion controlled
(from T. Pollard et al)

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

What life is really like: A cartoon from a 2011 review

My conclusion: The chemistry in cells is enormously

sophisticated, and it will probably take most of this century to gain a true understanding of how cells and organisms work

Because of evolution, the shortest path for working out the mechanisms in human cells will often start with molecular studies in simpler model organisms !

I can give you a personal example

I was a high school student, when the revolution in Watson biology began with the Watson and Crick structure for DNA in 1953

Crick

The Watson-Crick model for information transfer: DNA templating through complementary base pairs
A problem for the DNA replication mechanism: the two DNA strands run in opposite chemical directions

The next major breakthrough: the discovery of the enzyme that synthesizes DNA
1) The DNA polymerase enzyme was discovered by Arthur Kornberg and earned him a Nobel Prize. 2) This protein will add a new nucleotide to the end of one DNA strand (the primer strand ) only if that strand is paired to a complementary strand that can serve as the template (the template strand ).

The DNA polymerase in action

How we viewed DNA replication in the 1960 s

primer strand
5 3 DNA polymerase adds  one nucleotide and then dissociates

template strand
A second DNA polymerase molecule adds the next nucleotide

My dismal career as a graduate student, Harvard 1961-1965

Can we get the DNA double helix to replicate in a test tube? I did many experiments trying to see how this might happen using only the DNA polymerase enzyme. They all failed.

When I moved to Geneva Switzerland as a post-doctoral fellow in 1965, I discovered that DNA replication must require much more than the DNA polymerase

Bacteriophage T4, a large bacterial virus, had about 100 genes discovered by genetics by 1965

A major mystery in 1965: why were there at least 7 T4 genes that were absolutely required 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 to produce the T4 bacteriophage DNA polymerase. 3) Why are at least 6 additional proteins needed for any replication of the T4 chromosome when the virus infects the E. coli bacterium? 4) Clearly, DNA replication must involve at least 7 proteins and be much more complicated than anyone had imagined!

Result of 20 years of research at Princeton and UCSF

A protein machine

The magic of protein machines is best appreciated by a movie that shows such a machine in action. The movie was made by Bruce Stillman at the Cold Spring Harbor Laboratory, as part of the 50 year DNA celebration there. Download by Googling: YouTube Garland Science DNA.

We now know that the same basic mechanism is used to replicate DNA from large viruses, like T4 bacteriophage, to mammals
However, as more complex organisms

evolved, each function in T4 was carried out by more proteins For example, bacteria use 13 protein molecules instead of 7, and humans use about 40!

Two lessons learned in the last 20 years

1) Because of evolution, there are remarkable homologies between living things; therefore use model organisms wherever possible. 2) Nearly all cell processes will be:

driven by 10 to 20 proteins, organized as a protein machine and incorporating ordered protein movements driven by the energy of ATP hydrolysis based on elegant mechanisms that are too complex to predict.

An Important Challenge for the Next Generation of Cell Biologists

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 many hundreds of protein machines from their purified components, so that their detailed chemistry can be deciphered through reactions studied in a test tube. Then, we will also need to work out the many interactions between different protein machines

A cell is the fundamental unit of life What underlies its chemistry?

food in

waste out

Bacterial cells on the tip of a pin

Today s cells are very complex!

A Second Important Challenge for the Next Generation of Biologists

2). Completing our understanding of one type of cell. It is not enough to have a catalogue of all the pieces. We must also be able to explain how these pieces all add up to make a living thing. For this purpose, many laboratories will need to focus on the same, simple cell (for example, Mycoplasma, a tiny bacterium with only 500 genes compared to the 25,000 genes of humans).

The simplest living cell known, a tiny bacterium called Mycoplasma

Dividing cell, about to produce two cells from one

Why did multicellular organisms evolve on the earth?

Multicellularity permits cell specialization, with cells in different places having different functions for the organism as a whole. Consider a plant: the advantages include being able to have root cells deep underground to absorb water and leaf cells in the sun to carry out photosynthesis.

Many cells must cooperate to form a multicellular organism: but cooperation is very difficult!
Single-celled life was all there was on the earth for about 2 billion years. Finally, about 1.5 billion years ago, the first cells learned how to form cooperatives and larger and larger organisms began to evolve.

A simple multicellular organism: a cell cooperative

More complicated

Much more complicated

A very complex multicellular organism!

Thousands of billions of cells

A Third Important Challenge for the Next Generation of Biologists

3). Understanding how cells make decisions in a complex multicellular organism like ourselves. Cells constantly talk to each other. Then each cell integrates what it is hearing to control its behavior for the good of the entire assembly of cells that makes up the organism. We need to understand this complex process of cell thinking .

Signals coming from other cells

Cell signaling

Decision network in
one cell

A Fourth Important Challenge for the Next Generation of Biologists

4). Using our increasingly profound understanding of molecular cell biology to design intelligent strategies for improving human health. For example, rare aberrant cells give rise to the uncontrolled cell proliferation know as cancer. Once we truly understand how cells think , we can make these cells commit suicide without affecting the other, normal cells of the body.

A Fifth Important Challenge for the Next Generation of Cell Biologists

5). Deciphering the complicated pathways by which cells and organisms evolved on the Earth. Some powerful tools: comparative genomics, biochemistry, chemistry.

Learning from evolution: A comparison of genome sequences from Molecular Biology of the Cell

Where do we come from?

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

John s Science as a Way of Knowing series is available at www.SICB.org/dl/saawok.php3 Evolu=onary Biology. 1984. Amer. Zool. 24: 421-534.
Human Ecology. 1985. Amer. Zool. 25: 377637. Gene=cs. 1986. Amer. Zool. 26: 773-914. Developmental Biology. 1987. Amer. Zool. 27: 415732. Form and Func=on. 1988. Amer. Zool. 28: 443738. Cell and Molecular Biology. 1989. Amer. Zool. 29: 483812 Neurobiology and Behavior. 1990. Amer. Zool. 30: 403858. PLUS A Conceptual Framework for Biology Parts I, II, and III. Amer. Zool. 1989, 1990, and 1991 (These 3 total 300 pages!)

(from the Academy s Teaching about Evolu1on and the Nature of Science, 1998)

The chapter that I co-wrote with John

The challenge of science education

Two (sad) true stories: 1). A third grader returning from school, speaking to his scientist mother: Now I understand science. It is the same as spelling: you just have to memorize it because it does not make any sense.

The challenge of science education

Two (sad) true stories: 2). From Focus Groups of college-educated adults convened on behalf of the National Academy of Sciences: Science is what scientists believe; religion is what religious leaders believe. Both are equivalent, dogmatic belief systems and (with respect to evolution) I can chose either one.

Using Science magazine to create more coherence in the field of education

As Jay Labov emphasized this morning, how we teach our introductory college science classes is the key to any redefinition of science education!!

What scien=c socie=es can do

1). Work with other scientific societies to reshape college introductory biology courses so that they address all 4 strands of science proficiency in the National Academies Taking Science to School.
E.g., emphasize the importance of high-quality, low-resource lab modules that stress student inquiry, to replace the standard follow-the-instructions, cooking college laboratories.

2011 contest for best inquiry lab modules for introductory college science

 2). Work with other scientific societies to increase the importance and prestige associated with being a great teacher of science, at all levels.
Remember that Focus Groups suggest that a failure to understand the nature of science (John A. Moore s 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 the revealed truth from scientists has not worked!

Interactive, no lecture science classroom University of Minnesota (Professor Robin Wright)

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