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July 29, 2004


AGBIOVIEW NEWS FLASH: Francis Crick Dies; Co-Discoverer of DNA Structure


AGBIOVIEW NEWS FLASH: Francis Crick Dies; Co-Discoverer of DNA Structure

Francis Crick Dies


Francis Crick, who helped discover the double-helix structure of DNA, died 28 July after a long battle with colon cancer. He was 88. The discovery earned Crick and colleagues James Watson and Maurice Wilkins the 1962 Nobel Prize for medicine and revolutionized the fields of genetics and molecular biology.

Born in Northampton, England, in 1916 to a shoe manufacturer and his wife, Crick took to science early, conducting his first experiments before he was a teenager. He received a bachelor of science degree in physics from University College London in 1937, helped develop magnetic and acoustic mines for the British Navy during World War II, and earned his Ph.D. in 1954 at the University of Cambridge for using x-ray crystallography to decipher protein structures.

Crick met Watson at Cambridge in 1951, where they soon began working on one of the great mysteries of science: What was the structure of the molecule that stored each person's genetic information? Watson and Crick used their respective knowledge of genetics and x-ray diffraction, along with x-ray images from Rosalind Franklin and Maurice Wilkins, to determine the now iconic twisted ladder structure of DNA. The structure, published in 1953, immediately suggested a mechanism for DNA replication and has been the basis for everything from cloning to genetic engineering.

After the discovery, Crick continued to work on DNA, illuminating the mechanism by which DNA codes for proteins. Crick left the United Kingdom in 1976 to become a professor at the Salk Institute in La Jolla, California, where he began investigating the nature of human consciousness. In 1994, he published The Astonishing Hypothesis, a book that suggested that all aspects of human emotion and behavior could be understood by studying neural networks in the brain.

"He will go down as one of the most influential biologists of the 20th century," says Richard Murphy, president of the Salk Institute and a colleague of Crick's. Christof Koch, who collaborated with Crick on his consciousness studies, describes Crick as "the living incarnation of what it is to be a scholar," noting that the scientist continued to edit a manuscript on his death bed. According to Murphy, a new Crick-Jacobs Center for Computational and Theoretical Biology will be established at the Salk Institute to continue Crick's quest to understand the brain. Says Murphy, "His name will be listed among Darwin and Mendel as one of the true greats of science."



Francis Crick – Biography


Francis Harry Compton Crick was born on June 8th, 1916, at Northampton, England, being the elder child of Harry Crick and Annie Elizabeth Wilkins. He has one brother, A. F. Crick, who is a doctor in New Zealand.

Crick was educated at Northampton Grammar School and Mill Hill School, London. He studied physics at University College, London, obtained a B.Sc. in 1937, and started research for a Ph.D. under Prof E. N. da C. Andrade, but this was interrupted by the outbreak of war in 1939. During the war he worked as a scientist for the British Admiralty, mainly in connection with magnetic and acoustic mines. He left the Admiralty in 1947 to study biology.

Supported by a studentship from the Medical ResearchCouncil and with some financial help from his family, Crick went to Cambridge and worked at the Strangeways Research Laboratory. In 1949 he joined the Medical Research Council Unit headed by M. F. Perutz of which he has been a member ever since. This Unit was for many years housed in the Cavendish Laboratory Cambridge, but in 1962 moved into a large new building - the Medical Research Council Laboratory of Molecular Biology - on the New Hospital site. He became a research student for the second time in 1950, being accepted as a member of Caius College, Cambridge, and obtained a Ph.D. in 1954 on a thesis entitled «X-ray diffraction: polypeptides and proteins».

During the academic year 1953-1954 Crick was on leave of absence at the Protein Structure Project of the Brooklyn Polytechnic in Brooklyn, New York. He has also lectured at Harvard, as a Visiting Professor, on two occasions, and has visited other laboratories in the States for short periods.

In 1947 Crick knew no biology and practically no organic chemistry or crystallography, so that much of the next few years was spent in learning the elements of these subjects. During this period, together with W. Cochran and V. Vand he worked out the general theory of X-ray diffraction by a helix, and at the same time as L. Pauling and R. B. Corey, suggested that the alpha-keratin pattern was due to alpha-helices coiled round each other.

A critical influence in Crick's career was his friendship, beginning in 1951, with J. D. Watson, then a young man of 23, leading in 1953 to the proposal of the double-helical structure for DNA and the replication scheme. Crick and Watson subsequently suggested a general theory for the structure of small viruses.

Crick in collaboration with A. Rich has proposed structures for polyglycine II and collagen and (with A. Rich, D. R. Davies, and J. D.Watson) a structure for polyadenylic acid.

In recent years Crick, in collaboration with S. Brenner, has concentrated more on biochemistry and genetics leading to ideas about protein synthesis (the «adaptor hypothesis»), and the genetic code, and in particular to work on acridine-type mutants.

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 is now a non-resident Fellow of the Salk Institute for Biological Studies, San Diego, California.

In 1940 Crick married Ruth Doreen Dodd. Their son, Michael F. C. Crick is a scientist. They were divorced in 1947. In 1949 Crick married Odile Speed. They have two daughters, Gabrielle A. Crick and Jacqueline M. T. Crick. The family lives in a house appropriately called «The Golden Helix», in which Crick likes to find his recreation in conversation with his friends.


Francis Crick, DNA pioneer and English gentleman, dies

By Steve Connor http://news.independent.co.uk/uk/this_britain/story.jsp?story=546112

30 July 2004

Tributes were paid yesterday to Francis Crick, the British scientist and DNA pioneer who died at his home in California on Tuesday after a long battle with cancer. He was 88.

Crick shared the Nobel Prize in 1962 with James Watson, with whom he made the most momentous discovery in modern biology. He and Watson were working at the Cavendish Laboratory in Cambridge when, in 1953, they realised that the DNA molecule consisted of a double helix, a structure that opened up an explanation for the inheritance of genes.

Watson was seen as the brash young American, but Crick was the quintessential English gentleman, although he was radical enough never to accept the knighthood both were offered. Watson, a former head of Cold Spring Harbor Laboratory on Long Island, New York, said: "I will always remember Francis for his extraordinarily focused intelligence and for the many ways he showed me kindness and developed my self-confidence.

"He treated me as though I were a member of his family. Being with him for two years in a small room in Cambridge was truly a privilege. I always looked forward to being with him and speaking to him, up until the moment of his death. He will be sorely missed."

In addition to a Nobel Prize, Crick had a string of academic achievements. He became a fellow of the Royal Society in 1959 and won the Copley Medal in 1975, the Royal Society's premier scientific award.

Lord May of Oxford, the president of the Royal Society, said yesterday: "Francis Crick made an enormous contribution to science and his discoveries helped to usher in a golden age of molecular biology. His death is a sad loss to science."

Crick, whom Watson had once jokingly described as a man never known to be in a modest mood, was, in fact, a self-effacing man who did not court publicity. In his later years, he moved from Cambridge to the Salk Institute for Biological Studies in La Jolla, California, investigating the nature of human consciousness.

Richard Murphy, the Salk's president, said Crick will be remembered as one of the most brilliant and influential scientists of all time. "He will be missed a gentleman, a role model and a person who has contributed so much to our understanding of biology and the health of mankind," Dr Murphy said. Crick realised human consciousness was perhaps the biggest outstanding mystery of life on Earth. He said he wanted to excite younger minds than his to study the problem.

Professor Kristof Koch, a neuroscientist who collaborated closely with Crick at the Salk institute, said he never lost his impish ways. "Francis delighted in playing the important role of devil's advocate for several generations of young researchers," he said.

Crick, who was born in Northampton in 1916, started as a physicist and worked briefly for the Admiralty during the Second World War then returned to Cambridge to study for a doctorate. Asked in 1997 why he went into the study of DNA, Crick said that at the time he did not really know what he wanted to do.

"I used what I call the 'gossip test' to describe what I wanted to do. The gossip test is simply that whatever you find yourself gossiping about is what you're really interested in," he said. "I had found my two main interests I discussed the most were what today would be called molecular biology, what I referred to as the borderline between living and the non-living, and the workings of the brain."

Professor Steve Jones, the geneticist, said Crick was the Darwin of the 20th century, and the science writer Matt Ridley said Crick made more than one great discovery. "He found that genes are digital codes written on DNA molecules, he found that the code is written in three-letter words and he was instrumental in cracking the code," Dr Ridley said. "Any one of those would have got him a place in the scientific pantheon. Discovering all three places him alongside Newton, Darwin and Einstein."

David Giachardi, the chief executive of the Royal Society of Chemistry, said Crick's work on DNA cannot be underestimated. "He and Watson performed a gigantic service for humanity, and it the astonishing strides taken since his pioneering work are just the very beginning of a scientific journey for mankind," Dr Giachardi said.

Dr Roger Pederson, of Cambridge University, said: "What we owe Francis Crick cannot be said briefly because it is so vast. His legacy will be remembered for centuries."

Professor Richard Gardner, of Oxford University, said: "From my contact with him at Cambridge, I would rank Francis Crick as one of the greatest minds of the 20th century. He was a theoretician rather than an experimentalist, and was extremely perceptive."


Francis Crick dies


The master of science and arguably the founder of molecular biology was 88 | By Pete Moore

Francis Crick, known for his discovery with James Watson of the double helix but described as a biologist colleague as "the absolute master in a way that nobody else in that generation was," died yesterday (July 28) in San Diego, California. He was 88.

"If all you think of with Francis Crick is the double helix, then you don't know the man," Crick's Cambridge contemporary and Nobel prize winner Aaron Klug told The Scientist. Although Crick did perform many of the intellectual somersaults that revealed DNA's double helix – work for which he shared the 1962 Nobel Prize in Physiology or Medicine – that was only one of the world-changing discoveries that littered his career, according to Klug. While many of his achievements are now so established that they are the stuff of the school curriculum, in their time each was the pinnacle of scientific achievement.

Born on June 8, 1916 in Northampton, UK, Francis Harry Compton Crick in 1937 got a degree in physics at University College London, before spending World War II devising ways of sweeping German magnetic mines for the British Admiralty, and designing circuits for British magnetic and acoustic mines. During the war he also married Ruth Dodd, and the couple had a son, Michael.

Around the time that the war ended, so too did his marriage. In 1947 he married Odile Speed, and the couple had two daughters, Gabrielle and Jacqueline. 1947 also marked a significant change in his working life, as Crick moved to Strangeways Laboratory, Cambridge, where he studied the physical properties of cytoplasm in cultured fibroblast cells, a task he found intellectually limiting.

"He always knew who to go and talk to about problems," recalled Cambridge physiologist Horace Barlow. "He sought me out because he knew that I was interested in neuroscience. He was already working on a problem in cell biology, but he didn't think it was very important - all he wanted to do was get that finished with. He wondered whether to go into neurosciences."

After much thought, Crick headed for what is now called molecular biology. "He took his choice - and he was obviously right. He could have persuaded me to go into molecular biology, but I was such a bad chemist," Barlow said. So, in 1949 Crick joined the Medical Research Council research group in Cambridge. He wanted to bring science to the mysteries at the border between living and non-living. The team was led by Max Perutz, and Crick worked on protein structure, ending up doing a PhD on X-ray diffraction of proteins.

In 1951 James Watson arrived in Cambridge fresh from receiving his PhD at Indiana University in Bloomington, and the two instantly joined forces. Crick once said that their collaboration worked largely because they were never afraid to rigorously question each other's ideas, and the result was their Nature paper on April 25, 1953 that revealed the structure of DNA.

In 1957 Crick became excited about the Central Dogma, his theory that DNA passed its information to RNA, and this was then used to generate specific proteins. "Watson had something similar in his notebook, but Crick went around preaching it as certainty," said Richard Henderson, who first met Crick when he joined the Cambridge team as a PhD student in 1966. Then came the 'adapter hypothesis,' in which Crick realized that small molecules were involved in translating the RNA code-sequence into amino acids. These adapters turned out to be tRNA.

In 1958 he published a paper with his student David Blow in which they showed how to determine the structure of proteins using heavy atom derivatives. "The method dominated the field for decades," said Henderson, and Crick's 1959 election as a Fellow of the Royal Society confirmed his status in the field.

Crick began studying structure and function of histones in 1960. At the time, he thought that histones held the two chains of DNA apart for transcription. "That was wrong," Klug said, "but what Crick realized was that the 25 different histones were post-synthetic variants of four (it turned out to be 5) major types of histones."

The triplet codon became his next target, in 1966. Working with Sydney Brenner, Crick determined that each amino acid in a protein related to three bases in the genetic code. "That is the most beautiful elegant paper," Klug said.

Crick then came up with the wobble hypothesis. This theorized that while the first two bases in a triplet were always stringently complemented during tRNA's binding with mRNA, the third one was often less critically followed – there was an element of 'wobble' in the way that the code was translated into protein.

With thirty years of experience in molecular biology, and some 87 papers bearing his name, Crick made a radical shift in 1977. A long-standing colleague, Leslie Orgel, persuaded him to move to the Salk Institute in la Jolla, California, where he started studying neurobiology. "I thought he was the most brilliant guy, and it would be intellectually stimulating for all of us to have him around," Orgel told The Scientist.

With Graeme Mitchison, he investigated dreams, suggesting they were mechanisms for clearing out the debris of unwanted experience. With Orgel, he toyed with Panspermia – the theory that life developed on a far away planet and arrived on earth aboard a spaceship. But it was his interest in determining the neuronal correlates of consciousness that was his main passion over the following three decades. "He had a big influence in the Salk in building up their neuroscience program. It is now probably the foremost centre in the States, if not the world," Henderson said.

"When he started his work on consciousness, this was something no neuroscientist wanted to touch, it was not respectable," said Tomaso Poggio, professor of vision sciences and biophysics at MIT. "Now he has managed to make it work, to ask scientific questions about it to encourage others to do experiments on it. So, I think it has been an important contribution."

Starting in 1984, Crick started working extensively with neuroscientist Christof Koch, and together they co-authored most of Crick's papers associated with neuroscience. "Our theory was that consciousness involves specific neurons, firing in a specific way and sitting in a specific part of the brain," Koch told The Scientist. Their work focused on the visual system, and their working hypothesis is that while the primary visual cortex is important for vision, it does not generate ultimate conscious perception – in other words, the correlates are not in the primary visual cortex.

Back in Cambridge his absence was noted – particularly in seminars where he gained a reputation for grilling presenters. "He gave no quarter," said Klug. "He subjected you to criticism and expected you to stand up, though he was fairly kindly to young people. He didn't suffer fools kindly - that sums him up."

Crick's scientific method was rigorous. According to Klug, he learned it from the professor in charge of the Cambridge laboratory when Crick first arrived. He learnt sift though vast mounds of information and identify the reliable data. "He could reduce it to its essence" said Klug. "Then he was in a position to design experiments to test it, or else look for pieces of evidence from other people's work."

"Crick said to me in the early 70s that it difficult to imagine a problem that would not be solved in 25 years," said Michael Levitt of Stanford University, California. For Crick, he said, the trick was correctly formulating the question. For example, in 1998 he wrote a paper with Koch in which he sets out his rational for tackling the issue of consciousness. He beings by defining a few critical questions, at the same time as listing areas that are not worth approaching, because science is not ready to formulate questions.

"He was intellectually penetrating and rational, in a way that has been more successful than anyone else," Orgel said. This enabled him frequently to be decades ahead of the game. "He worked out the coil-coil structure of proteins before he sorted out DNA, but no one took much notice of it until a few years ago when it was shown to be quite correct – I thought that was really fun."
Links for this article
Francis Crick


Francis Harry Compton Crick (1916-2004)


Francis Harry Compton Crick, who co-discovered the helical structure of the DNA molecule in 1953 and went on to shape the early agenda of molecular biology, died this week in La Jolla, California. He was 88 years old.

Last year, the fiftieth anniversary of his DNA discovery, made with James D. Watson, was marked by celebrations around the world—an anniversary that coincided with the completion, more or less, of the sequencing of the human genome.

In honor of Crick’s contributions to DNA science and genomics, GNN highlights two entries about his work from our Genetics and Genomics Timeline.

In a landmark address to the British Society of Experimental Biology, entitled "On Protein Synthesis," Francis Crick proposed ideas that proved of the greatest importance to DNA research. Written for a general audience as much as for biochemists and molecular biologists, the paper became a classic that, as Horace Freeland Judson wrote in a historical appraisal, "permanently altered the logic of biology."


1953—Crick and Watson discover that the structure of DNA meets the unique requirements for a substance that encodes genetic information

Genes, by mid-twentieth century, were located to the chromosomes, known to be composed of protein and deoxyribonucleic acid, or DNA. The discovery of its molecular structure, by Francis Crick and James Watson, immediately suggested that DNA—not a protein, as was widely imagined—was the master molecule that contains the genes, self-replicates and recombines during reproduction.


A Visit With Dr. Francis Crick

Access Excellence Classic Collection, http://www.accessexcellence.org/AE/AEC/CC/crick.html
What follows is a transcript of a visit with Dr. Francis Crick, co-discoverer of the structure of the DNA molecule. Dr. Crick offers a fascinating look at the world of science at the time of this important discovery, as well as an equally fascinating glimpse into the thought processes of a brilliant scientist and thinker. This transcript is provided courtesy of Carolina Biological Supply Company.

Narrator: The 1953 discovery by Dr. Francis Crick and James Watson of the structure of the huge DNA molecule, the molecule which we now know stores the genetic information for all life, has been cited by many scientists as the single most important development in biology of the 20th century. Watson and Dr. Francis Crick's breakthrough, and the ensuing investigations into the nature of the genetic code and its transmission of information from generation to generation, have redefined the study of genetics and virtually created the science of molecular biology. For their work James Watson and Dr. Francis Crick, along with physicist Maurice Wilkins, were awarded the 1962 Nobel Prize in Medicine. Dr. Francis Crick recalls the award with his characteristic good humor.

Dr. Francis Crick: Well, I certainly didn't think I would win the prize. It's unclear whether Jim was thinking about it. He says in his book he was, but he never in those years mentioned it to me or to any other of my colleagues that I know of. It never occurred to me that it was prizeworthy until about three years later when someone mentioned it to me. And it indeed struck me this is just the sort of thing people get prizes for.

Narrator: Perhaps no one individual epitomizes the scientific theorist as does Dr. Francis Crick. Throughout his career in molecular biology, and later in neurobiology, Dr. Francis Crick has frequently eschewed experimentation preferring instead to concentrate his considerable genius on reading, thinking and talking his way to a problem's solution. Dr. Francis Crick's verve for a project has often been interpreted as immodesty, but his candid questioning of his colleagues, of himself, and most importantly, of their scientific methods has been instrumental in radically changing our world. His inquisitive nature has been apparent since childhood.

Dr. Francis Crick: I think I was always interested in science as early as I can remember. I don't think it was due to my parents. My father was a businessman. He never went to the university. My mother had been a teacher but she really didn't know about science. Whereas I wanted to know what is the world made of. And because I asked so many questions they bought me something called Children's Encyclopedia. And that covered all subjects. It covered history and literatures and music as well as science. And it had articles about the nature of the galaxy and chemistry and how things were made of atoms and so on. And I absorbed this with great enthusiasm and I think I must have at that stage decided to be a scientist. But I did confide to my mother, I said, "You know by the time I grow up everything would have been discovered." She said, "Don't you worry! When you grow up there will be plenty left for you to discover." So I think that is really how it happened.

Narrator: The young Crick attended Northhampton Grammar School and busily inquired into the nature of the world around him. At the age of 14 he entered Mill Hill School in North London - - where he obtained a thorough basic education in chemistry, physics and mathematics. Crick's undergraduate studies were at University College London where he received a degree in physics in 1937.

Dr. Francis Crick: As for the teaching, I studies physics with some mathematics. I didn't do chemistry because I didn't find that a very appealing subject. And I didn't do biology because people with my sort of background didn't do it in those days. I think the teaching was a little old-fashioned.

Narrator: Crick continued on at University College doing graduate work in physics until his research was interrupted by Word War II. After the war, however, he found himself less interested in physics and at a loss for a career. Meanwhile as interest in biology was ignited by Erwin Schrodinger's book What is Life? The Physical Aspect of the Living Cell. Crick became convinced that many fundamental problems in biology could be examined using the precise concepts and methods of physics and chemistry. In particular, he was eager to attack the doctrine of "vitalism" the notion that life processes are due to a vital principle not explicable by the laws of science.

Dr. Francis Crick: Well, I think what led me into biological research was really because I felt there was a mystery which I thought to be explained scientifically. And one of these areas was the borderline between the living and the nonliving and the other one was the problem of how the brain works - - the problems of consciousness. Of course nowadays we call those areas molecular biology and neurobiology, but those terms weren't known at that time. So after the war when I decided I would like to go back and go into scientific research, I realized I could start again and choose whatever field I wanted. And I found I was talking to friends about these particular problems. Although I knew nothing about them I was gossiping about them. And I thought that showed I was really interested. And then, after thinking about it further, I narrowed it down to what we call molecular biology and I looked around to see how I could start in that.

Narrator: For two years Francis Crick worked as a physicist, read and studied biology extensively, and bided his time until the opportunity presented itself to become involved in biological research. On his application for studentship to the prestigious Medical Research Council, Crick indicated his special interest in the division between the living and the nonliving. Thus, in 1949, one of the key performers in the search for the secrets of life found himself at the famed Cavendish physics laboratory in Cambridge, where many successful discoveries had occurred previously. Here scientists, working under the supervision of Sir Lawrence Bragg, were hoping to apply the working techniques of X-ray crystallography to better understand protein structure. At midcentury many scientists still believe that the family of macromoloecules called proteins contained the key to understanding the chemical basis of genetics. It was generally accepted that almost every cell has a complete set of instructions located in its genes and which determines how the cell grows, metabolizes and otherwise functions in relation to other cells. It was also thought that these genes reside on the cells chromosomes which were know to consist of both protein and deoxyribonucleic acid (DNA). Unlike most of his colleagues, however, Francis Crick remained unconvinced that proteins would hold the key to passing on genetic information.

Dr. Francis Crick: I think I first realized that the replication of genes was an important problem. And in that context one naturally wondered what genes were made of and one of the possibilities was DNA but it wasn't at all clear at that time that genes were partly made of DNA. There was some evidence which suggested that at least genes were partly made of DNA but no evidence to show they were entirely made of DNA. And so it was really in gene structure and gene replication I was interested in. And DNA was really only part of it.

Narrator: As Crick continued to learn about proteins and X-ray diffraction for his Ph.D. thesis, the second of the key characters in the search for the secret of life appeared at the Cavendish. In 1951 James D. Watson, a brash young American on a postdoctoral fellowship, and with a background in genetics appeared. The synergic charge of energy between the two men was instantaneous. Two scientists with complementary backgrounds found they shared a conviction that DNA, not proteins, was the critical factor in passing on genetic information from generation to generation. They both believed that solving the structure of DNA would lead to an explanation of the self-replication of genes. And they both were eager to learn quickly whatever was necessary to find answers. However, their pursuit of the DNA structure would encounter several obstacles.

Dr. Francis Crick: The major obstacle we had to overcome I think was ignorance. We didn't know much about the various things which you had to know in order to solve such a structure. So we had to teach ourselves. Course I knew about crysytallography and Jim learned about it. And we had to learn about organic chemistry. And we had to learn a lot of biological things to see if DNA was likely to be important. And we had to try to put all those together and avoid mistakes; and of course if you read what happened it's really a saga of our getting over one mistake after another until finally we cleared all the mistakes out of the way and then it was easy.

Narrator: Crick and Watson's efforts to understand what role, if any, DNA played in the replication of the gene required their assimilation of considerable bits of information from many sources. For example, by the turn of the century it was know that nucleic acids were present in all cells. Also established by then were the three essential ingredients of nucleic acids: a sugar (ribose or deoxyribose), a phosphate and various bases (made for the most part from nitrogen and carbon atoms). By this time also the five important bases had been identified: two structurally similar purines, called guanine (G) and adenine (A) and three structurally similar pyrimidines, called thymine (T) cytosine (C) and uracil(U). By the early 1920s it had been proven that there were actually two nucleic acids, ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). The structures of these different molecules are similar except that (1) the sugar in DNA (deoxyribose) has one less oxygen atom that the sugar in RNA (ribose) and (2) the thymine base of DNA is replaced by uracil in RNA.

Then, in 1944, Oswald Avery and his colleagues made a critical discovery that became a landmark for the fledgling science of biochemistry. Avery showed that purified DNA, not proteins, was the primary carrier of genetic information. (See Access Excellence Classic Collection: The Structure of DNA) Although it took years before Avery's discovery would be accepted by many scientists, the stage was set for Crick and Watson to investigate the role of DNA in the gene.

To suspect that DNA played a role in heredity was one thing; to determine exactly what that specific role was meant solving the structure of the DNA molecule. How big was the molecule? What shape? How could the structure of the molecule determine its ability to replicate itself and thereby pass information on from generation to generation? Surprisingly, Crick and Watson's backgrounds did not necessarily parallel their insights.

Dr. Francis Crick: What you might guess were the roles was not the case. It was obvious that I knew more about X rays and structures that Jim did and he had more background in biological things which I'd only roughly taught myself. So you might have guessed that I did the structural part and he did the more biological aspect. That really wasn't true. For example, . . . Watson discovered exactly how the base pairs went together, which is structural, he made that discovery. And I was the one who realized that the Chargaff's rules meant that things paired up which you didn't have to know any structure for, just something about the history of science. The things ... in the same amount ... usually go together...

Narrator: But perhaps the crucial ingredient in Watson and Crick's success was their affinity of temperament; both were fun-loving and ambitious, impatient to the point of officiousness and often mercilessly candid.

Dr. Francis Crick: The other thing that was helpful was ... that you have to be on such candid terms that when the other produces an idea you can criticize it very freely without being offensive and so on. So that means that if one of you gets an idea which is cul-de-sac, which gets you in off on a false trail, the other one will pull you back and get you out of it. And I think that's really what helped. That every time one of us had a false idea the other would be very critical about it. And there are a number of cases of that we can actually document.

Narrator: And indeed, like most scientists, Watson and Crick followed their share of false trails. The crucial problem centered around how the four bases could fit together within the core of the molecule. Readily available data from scientist Erwin Chargaff showed that a one-to-one ratio existed between adenine and thymine on the one hand and between guanine and cytosine on the other. However, working out the exact configuration of the base pairs required considerable time. At first using cardboard cutouts and later using metal plates, brass rods and screws provided by the Cadendish machine shop Watson built various trial models to illustrate possible molecular structures.

Dr. Francis Crick: Well, I think we first realized it came in several stages. I realized that we were probably going to see it when Donohue told us that we should have the correct tautomeric forms of the bases. We hadn't got them correct before. I think really we could see it when Jim got the base pairs and I spotted that they got the right symmetry. But of course until we'd actually built the first tentative model which was quite small, incidentally, it was only just half a base pair - until we'd done that we weren't sure. So there was a gap of about two or three days where we did the model building and checked that everything was all right. Then essentially we knew that... we had it. Of course, we were never totally confident it was right. And we actually had that built before we had seen the experimental data, except Jim had just seen this one picture, but we hadn't got any measurements. So the next stage of confidence was when we saw the experimental data and realized it fit very well with our ideas.

Narrator: Of course there were other important participants in the establishing of the double-helical structure of DNA. Maurice Wilkins and his colleague Rosalind Franklin, even though their inability to fully cooperate slowed the process, nevertheless provided the X-ray diffraction data that confirmed the basic model of the DNA molecule. Linus Pauling's remarkable innovation of building three-dimensional models showed the way to determine a molecule's structure with only a minimum of experimental evidence. And there were other contributors, but essentially it was the perseverance of Crick and Watson that led eventually to a moment of epiphany in the spring of 1953.

Dr. Francis Crick: My most vivid memory is the moment when Donohue told us that the bases existed in one tautomeric form. Because I can remember where I was standing which is always what happens in vivid memories. You remember all the irrelevant details. I was at my desk, the two of them were by the board. And I realized then if that was the case then it should be possible for the bases to go together. But I didn't do that. Jim did that the next day. But that was really quite a vivid moment. Of course once we got the idea we were rather euphoric about it because we saw it had the potential for solving so many problems. And we did build a slightly higher model - - not the great big one you see in the photographs - - that was built later. And naturally we told our colleagues and various people came along. Bragg was actually in bed with the flu at the time - - our professor. So he came in about a week later.

Narrator: Watson and Crick's three-dimensional model of DNA molecule exhibits the two sides of a flexible ladder coiled around a common center to form a double helix. Each outside of the ladder, often called the backbone, is invariant throughout the molecule and merely repeats the phosphate-sugar bond over and over again. Attached to the inside of the backbone at the sugar is part of the ladder's rung. This variable part of the DNA molecule consists of one of the four bases: adenine, guanine, thymine or cytosine. It is the exact sequence of these bases along the inside of the ladder that determines the genetic message. The key to Watson and Crick's discovery was the realization that because of its size, shape and chemical makeup, each base on one side of the ladder could pair by hydrogen bonds with only one other base on the other complementary side of ladder. Specifically, the large adenine molecule could pair with only the smaller thymine and the large guanine molecule could pair with only the smaller cytosine. Once this structural simplicity was grasped the mechanism for molecular replication became apparent: Each of the two strands of the double helix could, upon separation at the hydrogen bonds between the base pairs, serve as a template for the synthesis of a new complementary strand. Thus, two new strands - - each a replica of an original to create two double helices. While Dr. Francis Crick feels that he and Dr. Watson deserve credit for their discovery, he also recognizes that an eventual breakthrough was inevitable.

Dr. Francis Crick: Well, I think as far as we deserve credit in the case of DNA there are perhaps two things. One is for choosing the problem and realizing there was a problem about gene replication and what genes were made of, which most people thought was too difficult and ought to be left on one side. So we chose a difficult problem, course we weren't to know it was going to have such as easy and dramatic answer, but at least we chose the problem. The other thing I think we deserve credit for was persistence and trying and also for learning about a lot of different subjects so we could put it all together. And not many people were prepared to do that. They were prepared to learn about their own part of the subject but they weren't prepared to learn about X-ray diffraction, for example, if they were biochemists. And if they were people doing X-ray diffraction then the details of the biochemistry is often left to somebody else. So I think those were the two things - - choosing an important problem on the one hand and really sticking to it and going at if from many points of view. Well, if Jim and I hadn't discovered DNA, which easily could have happened, I think somebody else was bound to. The structure was there waiting to be discovered. And once you've seen the structure, I think the implications are fairly obvious although possibly if other people had discovered it, it might not have been pushed as much as Jim and I pushed it. The question then is who might have discovered it.

Narrator: After receiving his Ph.D. from Cambridge University in 1953 Dr. Francis Crick continued work to decipher the genetic code. Working with Watson, molecular biologist Sidney Brenner, physicist George Gamov and others, Crick showed how the sequence of four bases in DNA and RNA (ribonucleic acid) instructed the creation of the sequence of 20 basic amino acids which, it turn, coded for the thousands of proteins that direct the processes of life. Of course, the implications of their initial discovery are still being explored.

Dr. Francis Crick: Well, I think the effect has been dramatic because first of all it's laid a very sure foundation for all the molecular events that happened. Although, of course many of them we don't understand yet in detail but we think we understand in principle the sort of thing that proteins do, a nucleic acid does, even if we are finding new variants and so on as we go along. And then problems like those in developmental biology - - how you make a hand. Whole problems of embryology are now being transformed by these new methods and to say nothing of the applied problems, the medical ones. I mean we wouldn't even understand what a virus like AIDS was about if we didn't understand molecular biology. And the discoveries which were made about that type of virus - - the retoviruses - - built on the earlier discoveries.

Narrator: By 1966, feeling that the foundations of the molecular biology were adequately outlined and that it was time for him to pursue other interest, Dr. Francis Clark turned his attention to embryology. Then, in 1976, he went to the Salk Institute in La Jolla, California, for a sabbatical year from the Medical Research Council. The following year, after 30 years and 87 scientific papers, he decided to make a career change from the MRC and moved to the Salk Institute where he pursed his interest in the workings of the brain.

Dr. Francis Crick: When I started to think about the brain I had to decide what sort of things to do. I decided it was probably better not to do experiments.

Although even now there might be some things I might do experiments on, I decided I better do theoretical work. I also decided that I would mainly be interested in our brains and the brains of related animals--the higher mammals shall we say,--because there are many experiments you can't always do on human beings which you can do on rats or monkeys or whatever. And the other thing I decided was that I would try and not merely look at the molecular aspects which is what I knew about, but look at it from all levels from the psychological aspects and neuroanatomy and neurophysiology. Even some of the philosophical things and see if one could build bridges between the different approaches. And that is essentially what I have been trying to do.

Narrator: As part of Dr. Francis Crick's continued interest in the nature of the consciousness he also investigated the complex phenomenon of human dreams.

Dr. Francis Crick: Graeme Mitchison and I got into the business of dreams not because we were thinking about dreams, it was because we were thinking about neural nets. It is a common thought in the subject that you won't understand that brain by just understanding how one single neuro works. You must understand how groups of neurons interact and work together. And people make very crude and simple models of these which they can test their performance in a computer. These are called neural nets. The trouble is that they don't behave terribly well. When you store memories in them the memories are not stored as they are in a computer or a filing cabinet.. They tend to be stored rather on top of each other and they get in each other's way if you put too many in. We were worrying about this and wondered how you could prove that. We invented a mechanism which would, as it were, while the net was off-line, separate out memories which got a bit confused because they were too alive. And then it struck us that this is maybe what happened in sleep and REM, sleep the active sleep when you have dreams. Because the sort of mixtures that you get in nets are the sort of things you have in dreams, And we therefore thought this was some evidence for that.

Narrator: The nature of consciousness especially in the areas of vision memory and dreams still fascinates Dr. Francis Crick and will probably capture most of his attention in the future.

Dr. Francis Crick: Well it is always really difficult to say what you want to do in the future. I certainly would like of course to understand certain aspects of the brain better. But at my time of life it isn't obvious that I will actually do that myself. I might make a contribution myself I might promote other people into doing problems. The problem which I would most dearly like to see understood but I am not sure that will happen so soon is the problem of consciousness what makes us aware and so on.

Narrator: Perhaps more than anything else Dr. Francis Crick was, and continues to be, a creative thinker and adept communicator of ideas. In his book, Life Itself: Its Origin and Nature, Crick propounds the theory of directed panspermia that he and colleague Leslie Orgel developed to explain the origin of life on earth. This notion that life on earth was seeded by microorganisms from a higher civilization and sent through space on unmanned rockets remains outside the mainstream of science; however, the mental exercises that Crick entertains both for and against his theory are stimulating and informative. Francis Crick's most recently published book entitled What Mad Pursuit: A Personal View of Scientific Discovery ostensibly tells a familiar story about the discovery of the DNA double helix. However, the author, with his relaxed and personal style, quickly conveys that his enthusiasm for science for knowledge indeed for life itself has not diminished. Although he may not lead the charge as he did in the early days of molecular biology, Crick is eager to promote research on the brain and the nature of consciousness. In his epilogue he sounds the clarion for young scientists everywhere. The brain sciences have a very long way to go but the fascination of the subject and the importance of the answers will inevitable carry it forward. It is essential to understand our brains in some detail is we are to assess correctly our place in this vast and complicated universe we see all around us.


The Astonishing Hypothesis

From Wikipedia, the free encyclopedia.

The Astonishing Hypothesis is Francis Crick's book about consciousness. The book is mostly concerned with establishing a basis for scientific study of consciousness, but Crick places the study of consciousness within a larger social context. Human consciousness is central to human existence and so scientists find themselves approaching the topic after others have already claimed the territory. Crick does not try to avoid the resulting turf battle between scientists, philosophers, and the Catholic Church.

Public perceptions of science and the questions that scientists are willing to ask are strongly influenced by religion. Crick has discussed the relationship between science and religion in his earlier book What Mad Pursuit. Crick's view of this relationship is that religions can be wrong about scientific matters and part of what science does is confront the errors that exist within religious traditions. For example, the idea of a mechanism for the evolution of life by natural selection is opposed by some who fear that it undermines belief in creation of life by divine intervention. Crick's subtitle for The Astonishing Hypothesis is The Scientific Search For The Soul . Crick argues that traditional conceptualizations of the soul as a non-material being must be replaced by a materialistic understanding of how the brain produces mind. The publicity generated by opposition to scientific ideas such as natural selection or the scientific study of the soul brings such topics out of the rather obscure literature of science and into general public debate. In this book, Crick tries to hold up his end of this debate.

Those who oppose ideas such as natural selection are often frustrated by the difficulty of trying, as outsiders, to influence science and science education. This frustration sometimes results in emotional opposition to specific scientific ideas such as natural selection. The Catholic Church still advises scientists not to question the divine origin of the human soul. Scientists have learned lessons from public debate of topics such as evolution by natural selection. Many scientists now avoid public discussion of any topic that is part of religious doctrine. Crick is not one to avoid a confrontation between religion and science.

Francis Crick was one of the co-discoverers of the molecular structure of the genetic molecule, DNA. Crick served as an important theorist who helped guide the growth of molecular biology, the science that makes it possible for modern medicine to understand and combat diseases such as AIDS. More recently, Crick has become a theorist for neurobiology and the study of the brain. Crick's book The Astonishing Hypothesis boldly announced to the public that the human soul is a subject of scientific investigation.

In his book, Crick presented an idea that has great potential to provoke wide-spread public discussion and opposition. The 1990s were declared the Decade of the Brain by some administrators of science research. Within the rather small brain science community, researchers began discovering mechanisms of brain function that may account for the human soul. Few researchers care to inform the public of the implications of such research for fear of offending those who believe in non-material or eternal souls. Crick, as one of the icons of science, does not have to ask Congress for funding, so he is not afraid to confront the religious implications of modern neuroscience research.

In his review of Crick's book, J. J. Hopfield (Science magazine, 4 February 1994) concluded that, "The book should be read by scientists for its eloquent attempt to put consciousness, which we so much equate with the essence of our humanity, into the realm of science." Crick's book is an heroic attempt to wrest consciousness from the hands of philosophers and place it in the hands of scientists.

Crick's Astonishing Hypothesis is that, "a person's mental activities are entirely due to the behavior of nerve cells, glial cells, and the atoms, ions, and molecules that make them up and influence them." Crick shows how scientific study of the brain during this 1900's has brought us to the point where scientists can now accept consciousness, free will, and the human soul as subjects for scientific investigation.

There are many who feel threatened by the idea (to quote Crick) that, "You, your joys and your sorrows, your memories and your ambitions, your sense of personal identity and free will, are in fact no more than the behavior of a vast assembly of nerve cell and their associated molecules." Crick confronts these fears directly by using an unscientific word, soul. Crick is confrontational in his approach and challenges religious believers with the idea that there is a scientific view of the soul as being just one more manifestation of brain physiology.

For anyone with an interest in how their brain produces conscious experiences, Crick provides a guided tour of this largely unexplored territory. Crick argues that we need not fear this exploration. In coming decades, science may reveal the mechanisms of mind and provide humans with powerful means to control their brains. Crick's book is an invitation to understand this brave new world.

The Astonishing Hypothesis: The Scientific Search For The Soul (Scribner reprint edition, 1995) ISBN 0684801582