Crick & Watson 2

FRANCIS CRICK:

Born Francis Harry Compton Crick in Northampton, on 8 June 1916, elder of

two sons of Harry Compton Crick, successful boot and shoe manufacturer, and

Annie Elizabeth Wilkins. Attended Northampton Grammar School, and aged 14

won scholarship to Mill Hill School in North London. Four years later

entered University College, London, and received 2nd class degree in physics

in 1937. Remained at University College for graduate studies, conducting

research on viscosity of water at high temperatures, but work was

interrupted in 1939 by outbreak of WWII.

In 1940, Crick given civilian job at British Admiralty Research Lab, and

spent war yrs working on development of magnetic mines for use in naval

warfare. Same year, he married Ruth Doreen Dodd, and had son, Michael. In

1945, Crick was assigned to scientific intelligence at Admiralty HQ in

Whitehall to design weapons - worked on this for two years, and was during

this period that he read Schrodinger's 'What Is Life? The Physical Effects

of the Living Cell' (1944) - passage "How can the events of space and time

which take place within the . . . living organism be accounted for by

physics and chemistry?" Crick found bk so stimulating (although he laer

recognized its limitations in its neglect of chemistry), that - according to

what he called his "gossip test", which said that one should work on the

things one is talking and thinking about - the two subjects which he settled

on in 1947 for his life's work touched on problems which, in many circles,

seemed beyond the power of science to explain. "What attracted me to them

was that each contained a major mystery - the mystery of life and the

mystery of consciousness. I wanted to know what, in scientific terms, those

mysteries were."he decided to abandon plans for further degree in particle

physics and instead turned to biology - cd be seen as marking birth of new

discipline of biophysics.

Through support of Archibald V. Hill, in 1947 (now 31 - same yr divorced

wife) Crick obtained a Medical Research Council Studentship and began

working at the Strangeways Research Lab at Cambridge under direction of

Arthur Hughes. Here researched the physical properties of cytoplasm in

cultured chick fibroblast cells, meanwhile taking classes in biology,

organic chemistry, and techniques of X ray diffraction (method used to

determine 3D structure of molecules). In 1949 (yr married art student Odile

Speed), Crick moved to Cambridge's Medical Research Council Unit for

Molecular Biology at the Cavendish Labs, and became a research student for

the second time, being accepted as a member of Caius College, Cambridge. At

Cavendish Labs, he worked under chemists Max Perutz and John Kendrew on his

doctorate on molecular structure of proteins using X ray diffraction, and

there became interested in the genetic code for the amino acid sequence of

protein molecules. (Amino acids - of which are 20 types - are building

blocks of proteins). Fascinated by what he called "the division between the

living and the nonliving", Crick began looking for the chemical basis of

genetics, which he suspected cd be found in deoxyribonucleic acid.

By 1940s, researchers had discovered that genes are made of one of the

nucleic acids, DNA, and had also proved that genes or DNA direct the

biosynthesis, or production with living organisms, of cellular proteins

called enzymes, and thus control the biochemical processes of the cell. By

time Crick started Ph.D., was known that nucleic acids consist of DNA and

RNA (ribonucleic acid); that each is constructed of five-carbon sugar

molecules (deoxyribose or ribose), phosphate, and four nitrogen-containing

bases - adenine, thymine, guanine and cytosine (in RNA, uracil replaces

thymaine); and in 1950 Erwin Chargaff showed that DNA contains equal numbers

of adenine and thymine and of guanine and cytosine.

In 1951, Crick joined at Cavendish by biologist James Watson, visiting

American trained by Italian physician Salvador Edward Luria and member of

the Phage Group - group of scientists studying bacterial viruses

(bacteriophages, or phages). Like other phage biologists, Watson was

interested in discovering the fundamental substance of genes, and believed

that unravelling the structure of DNA was most promising solution to problem

of its role in the hereditary determination of the structure and function of

each cell. Crick and Watson soon developed informal partnership - Crick

brought knowledge about X ray diffraction and protein structure, while

Watson brought info on phage and bacterial genetics.

Meanwhile, in 1951-52, biochemists Maurice Wilkins and Rosalind Franklin at

King's College, London were using X ray diffraction to study the structure

of DNA and had demonstrated that phosphate groups probably lay outside the

molecule. Crick, learning of their work, urged F&W to build models - like

Linus Pauling had done to solve problem of alpha helix of proteins, thereby

demonstrating that proteins had a 3D structure and were not simply linear

strings of amino acids - but Wilkins and Franklin preferred more deliberate

experimental approach over theoretical, model-building scheme. Thus, while

working on their own projects, C & W spent next 2 yrs intermittently

discussing and arguing about problem until, in early 1953, they decided to

build own models of DNA. Using Franklin's X ray diffraction data (shown to

them, without her permission, by Wilkins) plus much trial and error, they

proposed a 3D structure for the DNA molecule that conformed both to London

group's findings and to Chargaff's data, and month later constructed a model

from beads, pieces of wire, and cardboard - model consisted of two

intertwined helical (spiral) strands of sugar and phosphate (deoxyribose

phosphate), joined by pairs of bases inside the helix, one adenine paired

with every thymine, and one guanine paired with every cytosine - the bases

attached to one another by hydrogen bonds. From this model, C&W theorized

(and other researchers went on to prove) on the replication of DNA: that two

parts of same molecule separate at the points of hydrogen bonding (similar

to opening of a zip), and that one new molecule is then synthesized opposite

each half of the old one - the sequence of bases acting as a template, or

mould, for the new molecule.

EB: "This copying process explained replication of the gene and, eventually,

the chromosome, known to occur in dividing cells. Their model also indicated

that the sequence of bases along the DNA molecule spells some kind of code

"read" by a cellular mechanism that translates it into the specific proteins

responsible for a cell's particular structure and function."

During spring and summer of 1953, Crick and Watson wrote 4 papers about the

structure and supposed function of DNA, first of which appeared in 'Nature'

on 25 April - accompanied by papers by Wilkins, Franklin and colleagues

presenting experimental evidence that supported the Watson-Crick model.

Watson won coin toss that placed his name first in the authorship, so now is

known as "Watson-Crick" discovery. First paper contains v. famous

conservative sentence: "It has not escaped our notice that the specific

pairing we have postulated immediately suggests a possible copying mechanism

for the genetic material." This paper was then followed up by more

speculative one a month later, that clearly argued for fundamental

biological importance of DNA. Both papers discussed at the 1953 Cold Spring

Harbor Symposium and received enthusiastic response; within a year,

Watson-Crick model began to generate broad spectrum of important research in

genetics.

After receiving his Ph.d. for a thesis entitled "X-ray diffraction:

polypeptides and proteins", Crick took leave of absence from Cambridge for

academic year 1953-1954 to work on the Protein Structure Project at the

Brooklyn Polytechnic in Brooklyn, New York, and also lectured on DNA

discovery at several universities (incl. Harvard) in U.S. He returned to

Cambridge in 1954, and continued research at Medical Research Unit at the

Cavendish, turning his attention to the relationship between DNA and the

genetic code. One of first projects was collaboration with Vernon Ingram,

leading to latter's 1956 demo that sick cell hemoglobin differed from normal

hemoglobin by a single amino acid. Ingram's research showed that a

"molecular genetic disease", caused by a Mendelian mutation, cd be connected

to a DNA-protein relationship. This hugely important for influence on

Crick's thinking re function of DNA, as it estbalished the first function of

the "genetic substance" in determining the specificity of proteins.

In 1956, the geneticist and molecular biologist Syndey Brenner joined Crick

at the Cavendish, and together they began exp. research on genetic mutations

in bacteriophage particles (viruses that infect bacterial cells) as a means

of working on "the coding problem" - i.e. how the sequence of DNA bases

would specify the amino acid sequence in a protein. This work was first

presented in 1957 in important theoretical paper given by Crick to Symposium

of the Society for Experimental Biology entitled "On Protein Synthesis", in

which he put forward group's ideas on the basis of the genetic code ("that

the specificity of a piece of nucleic acid is expressed solely by the

sequence of its bases, and that this sequence is a (simple) code for the

amino acid sequence of a particular protein"), and also correctly predicted

the mechanism for protein synthesis - that the first step, transcription, wd

be the transfer of information in DNA to RNA, and the second step,

translation, wd be the transfer of information from RNA to the protein -

hence, genetic message is "transcribed" to a messenger, and that message is

eventually "translated" into action in the synthesis of a protein.

By 1961 Crick and group had provided evidence: by this time, 3 types of RNA

had been discovered - messenger RNA, ribosomal RNA, and transfer (or

soluble) RNA. From their exps, Crick et al suggested way in which the

genetic code cd be read - according to Crick's theory, messenger RNA

receives genetic info from DNA in the nucleus of the cell and conveys it to

ribosomes (the sites of protein synthesis) in the cytoplasm, or nonnuclear

portion, of the cell. transfer RNA carried amino acids to the ribosomes;

messenger and ribosomal RNA then cooperate to join amino acids in the

correct sequence to form protein molecules. Crick described the genetic code

as consisting of triplets of DNA and RNA bases for each of the 20 amino

acids, with genes consisting of many base triplets - which Crick called

"codons". In other words, "each group of three bases (a codon) on a single

DNA strand designates the position of a specific amino acid on the backbone

of a protein molecule." (EB)

In 1962, Crick, Watson and Wilkins shared the Nobel Prize for Physiology or

Medicine "for their discoveries concerning the molecular structure of

nuclear acids and its significance for information transfer in living

material". Same year, Crick became director of the Molecular Biology Lab at

Cambridge, and a non-resident fellow of the Salk Institute for Biological

Studies in San Diego, Calif. During the 1960s, Crick and Brenner turned to

problems in developmental biology, eventually studying the structure and

possible function of histones, the class of proteins associated with

chromosomes. In 1966 he published 'Of Molecules and Man', which discussed

implications of the revolution in molecular biology.

In 1976, while on sabbatical leave from the Cavendish, Crick was offered a

permanent position as Kieckhefer Professor at the Salk Institute, where he

has remained ever since. Here, Crick began studies in neurobiology -

studying workings of brain, subject he had been interested in since

beginning of career. Meanwhile, working on book with Leslie Orgel entitled

'Life Itself: Its Origin and Nature' (1981), in which he pointed out

remarkable similarity among all life forms: wrote, "With the exception of

mitochondria the genetic code is identical in all living things so far

examined". Citing discoveries in molecular biology, paleontology, and

cosmology, he hypothesized that life on earth may have originated from

microorganisms that were disseminated through space from another planet

eventually reaching Earth and "seeding" it, and that this dispersal event

has been caused by the action of "someone" - theory he and Orgel named

"directed panspermia". Crick himself remained ambivalent about theory, but

he and Orgel proposed it as an example of how a speculative theory might be

presented.

Main thrust of his work has been entirely rationalist and fiercely reductive

however, based on

In his neurobiological studies at the Salk, during 1980s Crick chose to

study consciousness through the study of the mechanism of vision, and also

through the study of the function of dreams. In 1983 he and mathematician

Graeme Mitchison proposed that dreams are a side effect of a process through

which the human brain discards redundant or useless associations made during

waking hours - form of "reverse learning", which takes place, they

suggested, in order to prevent an overloading of neural circuits. Went on to

study mechanism of vision with Christof Koch, a computation and

neural-systems specialist from California Institute of Technology,

speculating on how the brain uses past experience - "either its own or that

of our distant ancestors, which is embedded in our genes" - to help

interpret the information coming into our eyes. Exps suggested that visual

awareness - and perhaps consciousness itself - involved the cortex and also

the thalamus

Crick published his autobiography, 'What Mad Pursuit: A Personal View of

Scientific Discovery' in 1988. This followed in 1994 by 'The Astonishing

Hypothesis: The Scientific Search for the Soul', in which he examined

whether what we commonly regard as soul or consciousness is actually a

neural machine, a neural machine. And he implores the scientific community

to tackle "the experimental study of consciousness and its relationship, if

any, to the hypothetical immortal soul." His "astonishing hypothesis" is

that all of our interior states, joys and sorrows, our memories and

ambitions, even our personal identity and the cherished notion of free will,

are no more than the behavior of a vast assembly of nerve cells" (idea thus

a "head-on contradiction to the religious beliefs of billions of human

beings alive today"), and in same book he claims to have located the seat of

free will inside the brain. This latter claim result of account he'd read by

colleague, well-known neurologist Antonio Damasio, of a woman who prior to

recovery from brain damage had suffered a loss of will - damage turned out

to be near anterior cingulate sulcus, region which receives many inputs from

higher sensory regions and is at, or near, the higher levels of the motor

system where movements are planned. Idea compounded by case histories he

then read regarding "alien hand" syndrome: kind of brain damage in which one

of patient's hands makes simple movements apparently against will of patient

• damage again in or near same region in brain. Appears to be directing much

effort towards total debunking of religion etc., but realizes that problem

of consciousness (100,000 yrs old) - being far more recent in evolution than

DNA (3 and half billion yrs old) - is likely to be far more complex and

difficult to solve. Predicts that while scientists "are basically tolerant

of religion, that may not last. There eventually will be conflict. We might

even see religious science wars. One would hope that could be avoided."

People outside the scientific culture, Crick says, "are naturally beginning

to feel threatened by scientists. And they are wise to feel that. They will

be threatened." - ie by idea soul a machine, no afterlife etc etc. Argues,

however, that though mystery may eventually go, science meanwhile replaces

this with awe for size of universe and complexity of life.

Awards etc.: Crick was made an F.R.S. in 1959. He was awarded the Prix

Charles Leopold Meyer of the French Academy of Sciences in 1961, and the

Award of Merit of the Gairdner Foundation in 1962. Together with J. D.

Watson he was a Warren Triennial Prize Lecturer in 1959 and received a

Research Corporation Award in 1962. With J. D. Watson and M. H. F. Wilkins

he was presented with a Lasker Foundation Award in 1960. In 1962 he was

elected a Foreign Honorary Member of the American Academy of Arts and

Sciences, and a Fellow of University College, London. He was a Fellow of

Churchill College, Cambridge, in 1960-1961, and received Royal Medal (1972)

and Copley Medal (1976) of the RS. Crick is still with second wife, Odile

Speed, now an established artist, with whom has two daughters, Gabrielle and

Jacqueline. Family lives in house named "The Golden Helix" at La Jolla,

where he has office and wife has studio. Has computer, but uses it for

accounting and domestic functions - prefers to work out scientific theories

in longhand.

JAMES DEWEY WATSON:

Born in Chicago, Illinois on 6 April 1928, only son of businessman James D.

Watson, and Jean Mitchell. Received early education at the Horace Mann

Grammar School and South Shore High School: was soon recognized as child

prodigy, and aged 12 was chosen to be one of the original Chicago Quiz Kids

(June 1940) on the NBC radio show of same name - appeared on it three times.

(Each week, five children between ages of 5 and 15 bombarded with questions

that wd stump most adult: top three scorers wd be on next programme - Watson

off after 3 goes cos cd not answer questions on Shakespeare and OT).

Shortly afterwards, in 1943, he enrolled at the Univ. of Chicago with

scholarship, aged only 15. Here pursued his interest in ornithology, and

received a B.S. in zoology from the Univ. of Chicago in 1947. As an

undergraduate he studied neither genetics nor biochemistry, an although

instructed by well-known population geneticist Sewall Wright at Chicago he

was still primarily interested in birds (ambition then to be curator of

birds at NYC's American Museum of Natural History), and in summer 1946 took

course in advanced ornithology at Univ. of Michigan. Did not become

interested in genetics until he read Erwin Schrodinger's book 'What is

Life?' (1944) in late 1946 - by amazing coincidence same bk that inspired

Crick etc. separated by more than decade in age and in 2 different

continents.

In 1947, Watson enrolled at Indiana University for graduate work: here was

Max Delbruck (mentioned in Schrodinger), German physicist who had trained as

physicist and immigrated to US in 1937, now working on bacteriophages and

member of American Phage Group. Watson studied under geneticist Hermann J.

Muller and the Italian bacteriologist Salvador Edward Luria, latter had fled

to US from Mussolini's Italy and now supervising Watson's doctorate which he

began in 1948. Watson's thesis was on the effect of X rays on the rate of

phage multiplication (bacteriophages = virus particles that infect

bacteria), and was awarded Ph.D. in zoology in 1950. Then received National

Research Council fellowship grant to study bacterial metabolism under

biochemist Herman Kalckar in Copenhagen, Denmark. While there he conducted

research on the biochemistry of DNA in the bacteriophage, but was becoming

increasingly frustrated with phage exps and wanting to learn more about

actual structure of DNA molecules: by this stage (early 1950s) had been

proved that DNA controlled the biochemical processes governing the cell,

neither the structure nor the function of the molecule was understood.

In spring 1951, while attending symposium and studying at Zoological Station

in Naples, Italy, Watson met Maurice H.F. Wilkins, who with Rosalind

Franklin at King's College, London had made X-ray diffraction studies of the

DNA molecule and had suggested that it might be a double helix, resembling a

ladder twisted into a spiral. Talking with Wilkins - who showed him blurred

X ray diffraction pictures of DNA - totally inspired Watson - now knew he

wanted to investigate the structural chemistry of the nucleic acids. Wilkins

suggested Cavendish Labs Cambridge as place to go as had another X-ray

diffraction unit there (belonging to Medical Research Council), and in Oct

1951, with a grant from the National Foundation for Infant Paralysis, he

went to Cavendish Lab at Cambridge Univ. to study the 3D structure of

proteins with John C. Kendrew, under direction of Max Perutz, who was

engaged in the X-ray crystallography of proteins. Here he met Francis Crick,

a physicist 12 yrs his senior who had switched to biology and was completing

his doctoral studies on protein structure.

Watson and Crick hit it off, and began discussing DNA problem. Between 2 of

them, had surprisingly little indepth knowledge of subject: Crick has only 2

yrs biology, Watson had no chemistry and no X-ray diffraction experience.

Nevertheless, both had overweening self-confidence, and in late 1951 they

set out to determine the structure of DNA. In November 1951, after Watson

had attended seminar by Rosalind Franklin at King's, London on her X-ray

diffraction discoveries, they built their first DNA model (both were certain

that answer lay in model-building - W. particularly impressed by Linus

Pauling's use of model-building in determining the alpha-helix structure of

protein). However, this first three-chain model proved totally wrong (as

Franklin pointed out in no uncertain terms when shown), because A-form DNA

F. had been using for photos was dehydrated, so in order to build up true

structure of DNA, one had to allow for added water. Although Watson had done

this, he'd figure wrong - their model had a tenth of the water it should

have done. When news of this reached Bragg, was angry as had broken

gentleman's agreement between Cavendish and King's re not interfering with

their research, and banned any more work on subject by C&W.

Intermittently over next 2 yrs, however, Watson and Crick continued to

theorize about DNA, but little progress as closed out of experimental data

at King's. In 1952 Watson determined the structure of the protein coat

surrounding the tobacco mosaic virus, but still made no great progress with

DNA until Jan 1953 when became galvanized by receiving copy of Pauling's

paper describing his DNA model. As it turned out, this wrong (as Watson

first to realize), and Watson instead inspired to try again with his own: in

spring 1953, having combined existing knowledge (including work by Chargaff,

Wilkins and Franklin's X-ray diffraction photographs - famous photograph 51,

ultra-clear of B-form, shown to Watson by Wilkins in late Jan 1953, without

F.'s knowledge, showing definite helical structure) with their own research,

and after receiving permission from Bragg to work on DNA problem again and

various models tried, Watson suddenly realized that the essential DNA

components - four organic bases - must be linked in definite pairs

(adenine-thymine pair, and guanine-cytosine pair) in a two-chain, rather

than three-chain, pattern. This realization was key factor in enabling W&C

to formulate a molecular model for DNA: month later, on Sat 7 March 1953,

they completed a 3D model of the model of the molecule made from beads, bits

of cardboard, and wire - two-chain model with bases on the inside and

sugar-phosphate backbone on outside. According to Watson-Crick model, DNA is

a double helix consisting of 2 strands of deoxyribose phosphate, joined by

pairs of bases that are analogous to the rungs of a ladder: through hydrogen

bonds, one adenine is paired with each thymine and one guanine is joined

with each cytosine. Method of self-replication explained by W&C as that the

2 parts of the DNA molecule separate from each other at the points of

hydrogen bonding - much like zip unzipping - and new molecule is then

synthesized opposite each half of the old one. Sequence of bases acts as a

template, or mould, for formation of new molecules. Discovery of chemical

structure of DNA widely hailed as most important biological developments of

the century.

After W&C published first description of theory (25.4.1953) and then their

model in the Brit journal 'Nature' in April 1953, they began working

separately. After completion of research fellowship at Cambridge, Watson

then spent summer 1953 at Cold Spring Harbor, New York, where biologist Max

Delbruck (one of "phage group") had gathered active group of investigators

working in near area of molecular biology. Later that year, Watson was

appointed senior research fellow in biology at the California Institute of

Technology in Pasadena, Calif., working with Delbruck and colleagues on

problems in phage genetics. He worked briefly with Crick again at Cambridge

(1955-56), on a structure for polyadenylic acid, and then in 1956 was

appointed assistant professor of biology at Harvard University, subsequently

becoming associate professor (1958) and full professor of biology (1961).

Watson, Crick and Wilkins received 1962 Nobel Prize for Physiology or

Medicine. By this time, Watson had essentially abandoned research,

publishing only one more research paper after receiving the prize - by early

60s had turned his attention to writing, began 'The Double Helix' in 1962,

and teaching (though apparently was often cruel and indifferent, though

brilliant, teacher).

While at Harvard, Watson conducted research on nucleic acids' role in the

synthesis of proteins and wrote 'The Molecular Biology of the Gene' (1965),

first widely used university textbook on molecular biology. In 1968, Watson

became director of the Cold Spring Harbor Lab of Quantitative Biology on

Long Island - place devoted entirely to research - while also maintaining

position at Harvard until 1976. While at Harvard, Watson also became v.

involved with science administration (this dominated last two decades of his

career), and esp in politics of science - setting research goals, obtaining

funding for research projects, bringing scientists together to work on

projects, lobbying Congress etc. During Harvard yrs he served in variety of

appointments, e.g. consultant to President's Scientific Advisory Committee,

member of a governmental project on biological warfare, member of a

boll-weevil eradication study group. In 1968 he married Elizabeth Lewis,

former lab assistant, with whom had two sons, and same yr published his

famous personal account of the DNA discovery and the roles of those involved

in it, 'The Double Helix: A Personal Account of the Discovery of the

Structure of DNA' - aroused much controversy, esp concerning his treatment

of Rosalind Franklin and her work.

In 1976, Watson retired as full professor at Harvard to devote himself to

Cold Spring Harbor, which became world centre for research in molecular

biology. In particular, at CSH he made major topic of study there viruses

and the cancers they cause in animals, and recruited some of best scientists

in world on project, created special new lab, got funding etc. In early

1980s he wrote 'The DNA Story' (1981) with John Tooze, and 'The Molecular

Biology of the Cell' (1983) with John Tooze and David Kurtz. Much of his

work has involved neurobiology and the role of viruses and DNA in cancer. In

1989, he was appointed director of the Human Genome Project of the National

Institutes of Health, project to map and decipher all of the genes in the

human chromosome, but resigned (1992) after less than 3 yrs in protest over

policy differences in the operation of this massive project (in EB says

"because of alleged conflicts of interests involving his investments in

private biotechnology companies"). Continues to speak out on various issues

concerning scientific research and is a strong presence concerning federal

policies in supporting research. In addition to sharing Nobel Prize, he had

received numerous honorary degrees from institutions, including one from the

Univ of Chicago, awarded in 1961, when Watson still in early 30s. Was

awarded Presidential Medal of Freedom by Jimmy Carter in 1977.

Candour/bluntness and general combativeness in public forums has often made

him unpopular, but on other hand scientific brilliance attested by Crick,

Delbruck, Luria and others. Still now at Cold Spring Harbor, aged 73.