The Human Side of Science: Edison and Tesla, Watson and Crick, and Other Personal Stories behind Science's Big Ideas (2016)

God touches DNA. Used with permission from Sidney Harris.

The greatest single achievement of nature to date was surely the invention of the molecule DNA.

—Lewis Thomas¹

JAMES WATSON'S DNA NOBEL PRIZE SELLS FOR $4.8M

Nobel medal. Courtesy of Anubis3, from Wikimedia Commons.

Yes, this headline from the December 5, 2014, BBC News involves the same James Watson who loved being around Leo Szilárd because he “got excited about something before it was true.” How in the world did Watson get a Nobel Prize for work he did at the tender age of twenty-five? And why did he sell the medal, the first living Nobel winner to do so? The answers to these questions involve several other people, and feature more than a few foibles, misunderstandings, competition among groups, faulty communications, and misjudgments—in other words, the usual suspects.

LEADER OF THE PACK

Let's start with the oldest of the participants in this drama, someone who turns out to be a key player—but at a distance: John Turton Randall (1905-1984)

John T. Randall (1905-1984). From BioMed Central Blogs, On Biology, Sept. 2, 2013.

John T. Randall was born in quite modest surroundings in Lancashire, England. At the University of Manchester, he earned a first-class physics degree in 1925 and an MSc in 1926. After graduation, Randall worked for General Electric Company, where he did research involving luminescent powders used in discharge lamps. Progress in identifying fundamental mechanisms responsible for luminescence earned him a Royal Society fellowship to the University of Birmingham, where he worked in Professor Marcus Oliphant's physics lab, starting in 1937. Oliphant's group at Birmingham included some fascinating characters, one of whom became so intertwined with Randall that the two cannot be separated: Maurice Wilkins (1916-2004).

SECOND IN COMMAND

Maurice Wilkins (1916-2004). From Wikimedia Commons, user Materialscientist.

Wilkins was born in New Zealand in 1916. When he was six years old, the family moved to Birmingham. Wilkins attended St. John's College, Cambridge, and earned his bachelor's degree in 1938. The degree was second-class, so he couldn't stay at Cambridge. He went home to Birmingham and approached Oliphant, who had been his instructor at Cambridge, telling Oliphant of his desire to pursue a research interest in luminescence. Since Randall had just joined Oliphant's group with the same research interest, Wilkins was hired, and he worked for Randall on a luminescence project for his dissertation.

The anticipated war helped catalyze some very interesting developments at the University of Birmingham. Professor Oliphant was asked by the British Admiralty to develop a compact, powerful microwave transmitter for radar use. Randall and his colleague Harry Boot worked on the radar problem, leaving Wilkins and his dissertation project minimally supervised. That was fine with Wilkins, who got a chance to meet a few physicists who had been funneled to Birmingham by the war. They included Klaus Fuchs, Rudolph Peierls, and Otto Frisch. You may recall from chapter 12 that Fuchs turned out to become a Russian spy, and Peierls and Frisch (Lise Meitner's nephew) made the critical mass calculation that showed the feasibility of the uranium-235 bomb. Since these physicists were all foreign nationals, security didn't allow them to work on radar.

Randall and Boot quickly produced a functional transmitter, which was improved upon by General Electric engineers, and revolutionized radar systems used by both England and the United States during the war. Meanwhile, Wilkins plodded along on his thesis project and produced two significant papers; he also coauthored with Randall, although Wilkins pointed out that Randall did none of the work. The papers were sufficient to get Wilkins his PhD in 1940.

With the radar problem under control, Randall left to teach for a year at the Cavendish Laboratory in Cambridge, continuing his transition from industry toward his eventual goal of academic life. The rest of Oliphant's group, including Wilkins, Peierls, Frisch, and Fuchs, went to the United States to work on the Manhattan Project. Wilkins worked at Berkeley on the uranium isotope separation problem and Peierls, Frisch and Fuchs went to Los Alamos. While in Berkeley, Wilkins married an art student named Ruth, who became pregnant and then divorced Wilkins before the baby, a son, was born.

ACADEMICS FOR REAL

Back in Scotland, Randall was appointed Professor of Natural Philosophy at St. Andrew's. He wrote to Wilkins and offered him a job in biophysics research. The recently divorced Wilkins accepted and sailed back across the Atlantic, which was then freed of U-boats. Wilkins told Britain's Encounter radio program in 1999: “After the war I wondered what I would do, as I was very disgusted with the dropping of two bombs on civilian centres in Japan.”²St. Andrew's was a bit out of the academic mainstream, and although the department thrived, Wilkins's personal research did not go well. Soon, he began exploring other avenues, principally around London and Cambridge. There were a few rows between Wilkins and Randall, but nothing serious. Fortunately, King's College London offered Randall the job of department head of physics and director of the Biophysics Research Unit. Randall accepted, and Wilkins joined him. Randall's Lab (referred to as Randall's Circus) was built in a bomb crater in the college's quadrangle. Money flowed in from many sources as government committees recalled the pivotal role of new ideas in wartime—especially Randall's radar. Randall's relaxed management style and the infusion of plenty of research grant money made for a happy and productive group.

ANOTHER KEY PLAYER

Francis Crick (1916-2004). Courtesy of Materialscientist, from Wikimedia Commons.

Wilkins's initial research efforts involved ultrasonic probes of many organic molecules, including DNA, but they met with little success. One day Wilkins was approached by a physics graduate student of similar age, Francis Crick (1916-2004). Crick's bachelor's degree was in physics from University College London, but his PhD work was cut short by the war. His dissertation topic was the viscosity of water at high temperatures, which he labeled “the dullest problem imaginable.”³

During the Battle of Britain, a bomb fell through the laboratory roof and destroyed Crick's experimental apparatus. Crick worked on underwater mines that could escape detection by minesweepers during the war. After the war, Crick became interested in applying physics to living systems and worked to determine the physical properties of cytoplasm at Cambridge's Strangeways Research Laboratories. Crick approached Wilkins, looking for a job in Randall's group. Wilkins took an immediate liking to him, regarding him as bright and energetic. The two became personal friends. When Wilkins told Crick of his personal research interests, Crick suggested Wilkins concentrate on proteins, not DNA. In spite of Wilkins's personal recommendation, Randall decided not to hire Crick, saying he was too boisterous and brash. Soon after, Crick joined the Cavendish Laboratory and explored the structure of proteins using X-ray diffraction.

DNA'S SIGNIFICANCE UNCOVERED

One of the King's College researchers, Geoffrey Brown, brought early news of key experiments that showed that DNA was the carrier of genetic information, so Wilkins's microscope research efforts were reduced so he could work more on DNA. Although he wasn't familiar with the techniques of X-ray crystallography, Wilkins was able to obtain very high-quality DNA samples for their research from Professor Rudolf Signer of Switzerland, a London conference participant. The only X-ray equipment the lab owned was designed to study relatively large single crystals, and so it was a bit large for the tiny DNA fibers. Nevertheless, research student Raymond Gosling (1926-2015) mastered the equipment, while Wilkins was able to prepare strands of the DNA on a tungsten wire frame. Randall suggested that air in the camera be replaced by hydrogen to sharpen the images, and part of a condom was used to seal the camera's hydrogen contents. The apparatus seemed cobbled together, but the results were the sharpest X-ray diffraction pictures yet. Not long after, the war surplus X-ray tube burned out, but the Chemistry Department offered the use of their large Raymax equipment so the work could continue. Some of the patterns obtained by Gosling implied that DNA might be wound into a helical (spiral) form. Reaching the limit of their equipment, they ordered a new fine-focus X-ray tube, along with a special micro-camera.

THE NEXT KEY PLAYER

To improve the lab's X-ray capability, in late 1950, an experienced X-ray researcher was added to the staff: Rosalind Franklin (1920-1958).

Franklin showed exceptional scholastic abilities from an early age and excelled at science, Latin, and sports. She went to Newnham College, Cambridge, and was awarded a fellowship to study physical chemistry at the University of Cambridge. She worked on classification of coals for fuels and gas masks, and earned her PhD in 1945. Next, she worked in Paris, applying X-ray crystallography to amorphous substances. Three years later, she accepted a fellowship to join Randall's group at King's College, London. Her original assignment was to work on X-ray diffraction from proteins and lipids in solution, but this initial assignment was redirected before it started.

Rosalind Franklin (1920-1958). From BioMed Central blogs, On Biology, July 25, 2013.

Here is a portion of the letter from Randall to Franklin:

4th December, 1950

Dear Dr. Franklin,

I am sorry I have taken so long to reply to your letter of November 24th. The real difficulty has been that the X-ray work here is in a somewhat fluid state and the slant on the research has changed rather since you were last here.

After very careful consideration and discussion with the senior people concerned, it now seems that it would be a good deal more important for you to investigate the structure of certain biological fibres in which we are interested, both by low and high angle diffraction, rather than to continue with the original project of work on solutions as the major one.

Dr. Stokes, as I have long inferred, really wishes to concern himself almost entirely with theoretical problems in the future and these will not necessarily be confined to X-ray optics. It will probably involve microscopy in general. This means that as far as the experimental X-ray effort is concerned there will be at the moment only yourself and Gosling, together with the temporary assistance of a graduate from Syracuse, Mrs. Heller. Gosling, working in conjunction with Wilkins, has already found that fibres of desoxyribose [sic] nucleic acid derived from material provided by Professor Signer of Bern gives remarkably good fibre diagrams.

CONFUSION BEGINS

This letter started the ball rolling on a misunderstanding that led to some significant consequences. Here's the next step in this dysfunction: When Rosalind Franklin began working at King's College, London, the first staff meeting wasn't attended by Wilkins, who was on holiday with a very attractive au pair who worked for some artist friends. Initial communication between Wilkins and Franklin was zero. For the next few months, Franklin cleaned up a few loose ends from her Paris assignment, then worked on setting up and fine-tuning the new X-ray apparatus and micro-camera. Franklin/Wilkins communication: still nothing substantive about DNA. Then, Wilkins made a presentation at Cambridge to protein X-ray workers, including Francis Crick. The talk included conjecture of the possible helical shape of the DNA molecule, its size, and its possible significance.

Wilkins DNA slide. Used with permission of King's College London © Raymond Gosling.

As Wilkins left the building, the first significant communication between him and Franklin occurred. Franklin told Wilkins in no uncertain terms that he should stop doing X-ray work on DNA. She said he should “go back to your microscopes!” In fairness to both Franklin and Wilkins, there was one phrase in Randall's letter to consider: “as far as the experimental X-ray effort is concerned there will be at the moment only yourself and Gosling.” Wilkins, on the other hand, had never seen the letter, nor had the issue been discussed with Randall.

Prior to this shocker, Wilkins had cemented himself firmly in DNA research by making interesting contacts with participants in DNA's past and future. Randall had been scheduled to speak at a conference held at the Zoological Station in Naples. The press of work was too great, so he sent his second-in-command, Wilkins, to summarize the activity at King's. Wilkins's talk was well received. He showed a slide that demonstrated clear X-ray diffraction of the DNA molecule in a photo taken by Raymond Gosling under Wilkins's direction.

In attendance was William Astbury, the pioneer in X-ray diffraction studies of DNA. Astbury had produced a similar photograph in 1939, but he acknowledged that Wilkins's results were much clearer. Also present was an extremely young fellow from America who was very excited about the potential crystalline structure of DNA as evidenced by the X-ray diffraction photograph. His name: James D. Watson.

THE LAST KEY PLAYER

James Dewey Watson was born in Chicago in 1928. As a youth, he never tired of asking why and spent hours poring over the World Almanac. He attended public schools and once won $100 on the TV program Quiz Kids. He was knocked out by a Jewish girl, Ruth Duskin (Feldman) on a Bible question.

Watson used the money to buy binoculars to continue the bird-watching hobby he shared with his father. In his own words, he was “far from the child genius,”⁴ but he entered the University of Chicago at age fifteen because Robert Hutchins, president of the University of Chicago, believed in “getting the kids into college two years earlier.”⁵

His first two years were not all that successful grade-wise, but Watson says they taught him three valuable things: read original sources, organize facts into rational schemes, and learn to think as opposed to relying on memorization. Dreams of ornithology took a backseat to genetics when Watson read Erwin Schrödinger's book What Is Life? in his senior year. By 1950, Watson had earned a PhD in zoology from Indiana University (at age twenty-two) and was hot on the trail of the molecule that controls genes: DNA. Postdoctoral work in the laboratory of biochemist Herman Kalckar focused too much on chemistry to satisfy Watson's DNA interests. But then came the meeting in Naples where Wilkins's X-ray slide captured Watson's imagination.

unidentified, James Watson, and Ruth Duskin (Feldman) in 1942. Reprinted from Whatever Happened to the Quiz Kids? Perils and Profits of Growing Up Gifted, by Ruth Duskin Feldman.

THE TEAMS ARE IN PLACE

The Medical Research Council Unit for the Study of Structure of Biological Systems got a new member in September 1951: James D. Watson. Located in the Cavendish Lab at Cambridge, the small group was headed by Max Perutz, a chemist who had been collecting X-ray diffraction data on hemoglobin molecules for ten years. Head of the entire Cavendish Lab was Sir Lawrence Bragg, a Nobel Prize-winner in Physics for being the pioneer of X-ray crystallography. Bragg still participated in the research, trying to interpret the experimental results in terms of molecular structure. The unit also included John Kendrew and Hugh Huxley, who mostly worked on muscle cells. Rounding out the unit was Francis Crick, whom we met earlier in this chapter.

Recall that Crick had been a physicist before and during the war, but he changed to biophysics, possibly influenced by his reading of Schrödinger's book. At the Cavendish, Crick's thesis topic was protein crystallography, but his wide interests and ebullient personality carried him far afield. Although he was pleasant and polite, he visited many different labs and offered his opinions about theory at high volume to anyone who was interested. His explosive laughter made it impossible for him to hide, not that he was wont to do so. Crick and Watson shared an office at Cavendish, and Watson tried his best to interest Crick in his DNA quest. Crick had worked on protein structure for two years and wasn't prepared to jump ship quickly. Besides, DNA structure was being studied in another lab at King's College London by the disjoint team of Wilkins and Franklin. Complicating the competitive picture between the Cavendish and Randall King's group was the personal friendship between Crick and Wilkins.

FIRST SCORE: KING'S TEAM

Working away on X-ray diffraction, Franklin soon discovered that there are two distinct forms of DNA. One form was labeled “A,” in which the molecules are less hydrated and shorter, while the other, more heavily hydrated form consisted of longer molecules and was labeled “B.” Wilkins took the opportunity to suggest to Franklin that they work together, but Franklin angrily refused. Randall imposed a settlement by assigning research on the A form to Franklin using the excellent Signer DNA samples, while Wilkins would work with the B form using samples obtained from biochemist Erwin Chargaff at Columbia University. The Chargaff samples turned out to be too degraded for effective X-ray studies, so Wilkins made little progress.

CAVENDISH TEAM'S TURN

Meanwhile, at the Cavendish, Watson and Crick decided to take a new approach. Although neither one was technically assigned to analyze DNA, their fascination drove them to take a page from a master's book. Earlier in 1951, American chemist Linus Pauling at Caltech had scooped everyone, but most irritatingly the Cavendish lab, by discovering the basic structure of proteins—the alpha helix. This was just the latest triumph for Pauling over Bragg, who was Pauling's chief competitor. Part of Pauling's solution technique was building physical models of the molecular components, then fitting them together.

In November of 1951, Crick and Watson built a physical model of the DNA molecule as a three-chain helix with phosphate groups on the outside. Part of the basis of the model was Watson's recollection of the water content of the molecule in a presentation by Franklin. Crick invited Wilkins to come to the Cavendish to see the model. Wilkins accepted and brought his collaborators Bill Seeds, Bruce Fraser, Franklin, and Gosling the following day. The visit was a disaster for Crick and Watson. Franklin pointed out that the water content was all wrong (faulty memory of Watson) and the molecule wasn't proven to be helical in her research. In her view, model building should only be attempted when the structure is well known, which it certainly was not.

BRAGG'S MORATORIUM

As a direct result of the meeting, Bragg, directed that Crick and Watson should give up their DNA work and leave the DNA analysis to King's. Crick and Watson showed evidence of their cooperation by sending copies of the metal jigs they had used for model building.

Photo 51. Used with permission of Kings College London, © Raymond Gosling.

All was quiet for most of 1952. Crick worked on his thesis topic, the structure of hemoglobin; Watson took up the topic of the tobacco mosaic virus (TMV), a convenient cover since it has a substantial DNA component; and the King's group continued their X-ray diffraction experiments. Franklin's work provided no confirmation of a helical structure for DNA. She sent Alex Stokes (mentioned above in Randall's letter to Franklin) and Wilkins a prank notification of the death of the DNA helix. Wilkins and Stokes took this joke somewhat more seriously than intended, however. In fact, Franklin could find no good evidence for helical structure in the A-form, but she never suggested the B-form was anything but helical. In fact, one of the photographs taken by Gosling in May of 1952, the now-famous Photo 51, showed very clearly the helical nature of the B-form of DNA.

CATALYSTS

In chemistry, a catalyst is a substance that assists a chemical reaction without becoming a permanent part of the products. In 1952, there were two human catalytic agents whose actions had a direct bearing on the determination of DNA structure. The first was Rosalind Franklin, when she chose to leave King's. In June, Franklin decided to spend the third year of her fellowship at Birkbeck in the lab of Professor J. D. Bernal. Randall was notified, asked Franklin to leave all her DNA work at King's and to not continue studying DNA at her new position. The second catalyst consisted of two young Americans who arrived in the late fall to work at Cavendish: Peter Pauling (oldest son of Linus Pauling) and Jerry Donohue. Donohue shared the office with Watson and Crick, and Pauling spent a lot of time with the group. These catalysts combined to help win the DNA structure race for Bragg's Cavendish laboratory.

Hang on, the slow pace of normal research is now accelerated as rapid progress was then made, culminating in the determination of the structure of DNA.

· Christmas 1952: Linus Pauling announced in a letter to his son Peter that he has solved the structure of DNA. Peter passed this along to Watson and Crick, who were disheartened but pressed on regardless. They had agreed not to work on DNA, but they couldn't stop thinking about it.

· January 28, 1953: Rosalind Franklin, at her last seminar before leaving, summarized her work on the A-form of DNA but made no mention of a helix or anything else about the B-form.

· January 28, 1953: Two preprints of Pauling's paper arrived, one to Peter and one to Bragg. Watson grabbed Peter Pauling's copy and scanned it hurriedly. He was overjoyed to note that Pauling's model was quite similar to the Watson/Crick model from 1951—and therefore, wrong. On the other hand, Pauling was on the trail, and it probably wouldn't take him long to correct his errors.

· January 30, 1953: Watson rushed to King's and offered to show Pauling's paper to Franklin. In a scene judged to be confrontational by Watson, Franklin implied that she was busy and not interested in more faulty DNA structure arguments. Watson beat a hasty retreat and ran into Wilkins. Wilkins was interested in Pauling's error, and showed Watson Photo 51, which had been given to him by Gosling. Instantly, the strong X-pattern revealed to Watson the helical nature of the DNA molecule.

· February 1953: Cavendish lab director Bragg turned Watson and Crick loose to allow them to return to building a DNA model. He was not about to lose another competition to Pauling. Wilkins also agreed that Watson and Crick could go back to working on DNA. As their model building ran into snags, Jerry Donohue suggested they use a structural variation on their molecular bases. It worked beautifully.

Watson and Crick with DNA model. © A. Barrington Brown / Science Source.

· Early March: After a bit of fiddling, the Watson/Crick model of DNA was complete. They invited many to see it, and it withstood all criticisms. The full paper is available online.⁶

In 1962, the Nobel Prize in Physiology or Medicine was awarded to Crick, Watson, and Wilkins “for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material.”⁷ The chemistry prize was given to Perutz and Kendrew, “for their studies of the structures of globular proteins.”⁸ Linus Pauling wasn't shut out completely. He won the 1962 Nobel Peace Prize.

Bonus Material: Franklin/Wilkins Internet interview. See To Dig Deeper for details.

AFTERMATH

The exclusion of proper Nobel credit for the critical work of Rosalind Franklin created a controversy in the mid-1960s, but Franklin's death from ovarian cancer in 1958 precluded any real Nobel credit, since the prize is awarded only to living scientists. Her work at Birkbeck on the tobacco mosaic virus was top-notch, and she amassed well-deserved credit. Franklin remained scientific and personal friends with Francis Crick and his wife, Odile, until her death.

In his 1968 book The Double Helix, James Watson tends to caricature Franklin, referring to her as “Rosy,” and “Wilkins’ assistant.”⁹ In response, a book written by Anne Sayre (Rosalind Franklin and DNA [New York: W. W. Norton, 2000]), a personal friend of Franklin's, set the record straight, pointing out that “Rosy” was an aunt in the Franklin family, not a preferred nickname for Rosalind, and that Franklin was hired as a far more experienced X-ray analyst than Wilkins, and not just an assistant.¹⁰

Some think the pendulum has swung too far, and Franklin, as her younger sister Jenifer Glynn puts it, “has become ‘the forgotten heroine.’ Her story has been adopted by feminists as a symbol of a woman struggling and unacknowledged in a man's world. This would, I think, have embarrassed her almost as much as Watson's account would have upset her. It suited the feminism of the 1960s and 1970s to portray her as a victim of male dominance, but she would have thought of herself simply as a scientist whose achievements should have been judged on their own terms.”¹¹

KUDOS

John Turton Randall was knighted in 1962 and retired to Edinburgh in 1970.

Used with permission from Sidney Harris.

Maurice Wilkins became a Fellow of the Royal Society in 1959, the same year he married Patricia Chidgey. Wilkins remained at King's College London until he retired in 1981. He became president of the British Society for Social Responsibility in Science in the late sixties and continued in that position for twenty years. In 2003, he released his autobiography, The Third Man of the Double Helix.

Raymond Gosling was a fellow in an awkward position: supervised by two people who didn't get along and dependent on them to get his PhD. Fortunately, he had a good sense of humor. He called Randall “JT” or “the old Man” or “King John.” When he was assigned to Franklin, Gosling said he was “the slave boy handed over in chains.” He called Wilkins “uncle Maurice.”¹² Since he was involved in taking so many critical X-ray diffraction pictures, Gosling might have written a book titled The Fourth Man of DNA, but he didn't. He received his degree in 1954 and lectured in physics at St. Andrew's and the University of the West Indies. He then became a lecturer and reader at Guy's Hospital Medical School, London.

Francis Crick completed his dissertation and received his PhD in 1954. He did his postdoctoral work at Brooklyn Polytechnic, then went back to Cambridge until 1976. Later, he went to La Jolla, California, to the Salk Institute and worked on neuroscience, eventually studying consciousness.

James Watson taught biology at Harvard from 1956 to 1976. In 1968, he wrote the book The Double Helix. In the preface, he notes: “I have attempted to re-create my first impressions of the relevant events and personalities rather than present an assessment which takes into account the many facts I have learned since the structure was found.”¹³ The book delivers on this promise and generated much controversy in the process. Some of the “Rosy” comments are detailed above, but Francis Crick was none too happy with the book either. Watson seems comfortable with controversy, self-generated or not. Fellow Harvard professor Edmund O. Wilson called Watson “the most unpleasant human being I had ever met.”¹⁴

Watson became director of Cold Spring Harbor Laboratory, New York, in 1968 and continued in that position until 2007. In that same year, he was quoted in the Times of London as saying “[I am] inherently gloomy about the prospect of Africa [because] all our social policies are based on the fact that their intelligence is the same as ours—whereas all the testing says not really.”¹⁵ He went on to say that despite the desire that all human beings should be equal, “People who have to deal with black employees find this not true.”¹⁶ The furor this quote generated led the trustees of Cold Spring Harbor to ask for his retirement. He is now Director Emeritus of Cold Spring Harbor Laboratory.

And as for auctioning the Nobel medal, it was bought by Alisher Usmanov, a major shareholder in the Arsenal Football Club and said to be the richest man in Britain. In a ceremony, the medal was returned to Watson, and the tycoon said he was “distressed” that Watson felt forced to sell it.¹⁷

So, what was the motivation for the sale? Several quotes from Watson have a bearing here:

“No-one really wants to admit I exist.”

“I want to re-enter public life.”

“I really would love to own a [painting by David] Hockney.”¹⁸

Another possible influence might relate to the fact that Francis Crick's seven-page handwritten letter to his son explaining the DNA discovery had just sold in 2013 for six million dollars, an all-time record for the auction of a letter.

Oh, one last thing. Watson served as head of the Human Genome Project from 1988 to 1993. That project and its aftermath are the subject of the next chapter.