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For anything and everything on science from India | ||||||
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Dr
Subodh Mahanti |
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The year 2003 is the fiftieth year of the discovery
of the DNA structure—the double helix. However, the debate
about the share of credit due to Rosalind Elsie Franklin for the
discovery of the structure of DNA continues. And perhaps it will
continue. Crick, Watson and Wilkins who shared the Nobel Prize in
Physiology or Medicine in 1962, did not refer the contributions
of Franklin in their Nobel Lectures. Watson in his personal account
of the discovery of the DNA structure, which was published in 1968
under the title The Double Helix: A Personal Account of the Discovery
of the Structure of DNA, dismissed Franklin as unattractive, unfriendly
and unimaginative. In any case Watson’s account was statedly
one-sided. Watson did not attempt to hide this fact. He wrote what
he felt. However, it should be pointed out that if one reads Watson’s
account carefully one would realize that Watson did not try to undermine
the importance of Franklin’s contribution. Anne Sayre, a friend
of Franklin, in her book, Rosalind Franklin and DNA, published in
1975, established Franklin as feminist icon who was cheated of due
recognition for the discovery of the DNA structure. In a recent
book titled Rosalind Franklin: The Dark Lady of DNA by Brenda Maddox
it has been argued that Franklin was instrumental in discovering
the structure of DNA and her contribution was not altogether ignored.
Maddox has argued that Franklin would have got the Nobel Prize,
if, she was not dead. The Nobel Prize is not given out posthumously.
Franklin was an outstanding scientist. She was totally devoted to
science. In those days it was not easy for a woman to pursue a scientific
career. Franklin had to face opposition from her own family members
when she decided to pursue higher studies in science. There is ample
evidence that being woman she was at disadvantage while working
at Cambridge. She died of cancer at the age of 37. And there is
no denying the fact that the importance of Franklin’s was
lost of sight because of her untimely death. In this article our
attempts would be to give some glimpses of what have been written
on Franklin’s life and work, with the hope that readers will
be motivated to know more about this remarkable woman, and a highly
accomplished scientist. Franklin’s work on tobacco mosaic virus was very important. It was Franklin who first showed that the tobacco mosaic virus (TMV) was not solid, as had been thought but a hollow tubular structure. After TMV Franklin started working on polio virus. Rosalind Franklin was born on July 25, 1920 to prosperous Jewish parents, Ellis Franklin and Muriel Franklin (nee Waley). Franklin’s father was a prominent banker. Her family was active in community service. Franklin attended the St Paul’s Girls’ School, one of the few girl’s school in London that taught science. At school Franklin was an excellent student and she developed a strong liking for science. She decided to become a scientist. However, her father did not like her decision, as he was not in favour of higher education for women. He was of the view that women should marry and do charitable work. So Franklin’s decision created a family dispute and after being persuaded by other family members Franklin’s father relented. She was allowed to attend a college of her choice. She attended the Newnham College in Cambridge, from where she graduated with a BA in 1941. After getting a research scholarship from Newnham, she started doing her research work for her PhD degree under the guidance of Ronald George Wreyford Norrish (1897-1978). However, she did not work with Norrish for long. The second world war was in progress. Franklin was keen to take her part in the war effort. Towards this end she joined the staff of the British Coal Utilisation Research Association (CURA) as Assistant Research Officer in 1942. The CURA was an industrial organization. It was established in 1938. At CURA Franklin worked on the problem of making coal more efficient. Her work concerned the microstructures of coal. She published five research papers while working at the Coal Utilisation Research Association. Based on this work Franklin obtained a PhD degree of the Cambridge University in 1945. In 1947 Franklin moved to the Laboratorie Centrale des Services Chimique de L’Etat in Paris. Here she learned about X-ray diffraction, at that time it was considered as a relatively new and promising technology. When Franklin took up X-ray diffraction work, the subject was little more than 30 years old and it was expanding rapidly. She established herself as an expert in creating and analyzing the photographs of biological molecules. In Paris she mostly worked with Jacques Mering. She published a seires of important papers on graphitising and non-graphitising carbons. On her work on coal J. D. Bernal wrote in London Times (April 19, 1950): “She (Rosalind) discovered in a series of beautifully researches the fundamental distinction between carbons that turned on heating into graphite and those that did not. Further she related this difference to the chemical constitution of the molecule from which carbon was made. She was already a recognized authority in industrial physico-chemistry when she chose to abandon this work in favour of the far more difficult and more exciting fields of biophysics.” In 1951 Franklin accepted a three-year research
position at King’s College, London. At King’s College
she was specifically recruited to work on biological molecules.
Sir John Randall, Director of the Biophysics Unit of the Medical
Research Council at King’s College, where Franklin was appointed,
had specifically instructed her to work on DNA using the X-ray crystallographic
techniques she had learned at France. As we know this technique
provides a pictorial mapping of atoms. After coming to King’s,
she soon learned that Maurice Wilkins, another researcher at King’s
College, was already working on DNA, using X-ray and other methods
In the absence of proper communication Wilkins assumed Franklin
as his subordinate. Sayre has described the situation in the following
way: “It seems never to have been clearly defined what Rosalind
was to do at King’s—which would not have mattered, of
course, if such general friendliness had prevailed that definitions
were unnecessary. But Rosalind had her own idea of what she was
there for, Wilkins may well have had a somewhat different one, and
the uneasiness naturally produced by such differing notions was
not soothed, or clearly resolved, by Randall, who was probably unaware
of the uneasiness until it had developed into a good deal more than
that.” Franklin felt unable to cooperate with Wilkins and
she had not much respect for the early attempts of Watson and Crick
towards working out of the structure of DNA at Cambridge. So from
the start the relation between Franklin and Wilkins was bad. It
never improved, rather with the passage of time it worsened. If
they had developed a good working relation then the history of double
helix would have written in a different way. Perhaps there could
have been a number of reasons for the hostility between Franklin
and Wilkins. The most important reason was, as mentioned above,
that nobody really knew what Franklin’s exact duties were
at King’s College. She was told by Randall to work on DNA
but then Wilkins was already working there on DNA. So one side Wilkins
thought that Franklin was supposed to assist him but on the other
side Franklin felt no reason to work under Wilkins, as she was specifically
brought there to work on DNA because of her experience in the field.
Rosalind had to develop her filed on her own at King’s. At
the time Rosalind came to King’s there was no strong X-ray
diffraction group. It had to be created. She had to make suitable
equipment for her studies. So she legitimately felt no reason to
work under someone. Many people would tend to blame Randall for
this misunderstanding. The other important reason was that Franklin
was a woman. Today this statement may seem to be quite illogical.
Women are not discriminated in universities or research institutions,
at least officially. Things were different in those days. The presence
of women in scientific pursuit was not welcome, rather it was considered
as an intrusion by their male counterpart. So she had to face a
male hostility, though invisible on the face of it. In those days
in Cambridge women were not allowed in university dining rooms and
many of her colleagues went to male-only pubs for after-work socializing.
To quote Sayre: “Rosalind was not a man…from the start,
she was dealt with at King’s less as a scientist than as a
woman, hence inferior. This inferiority has been deduced, but there
is evidence which implies it. It is minor thing, but perhaps not
so very minor, that in those days the male staff at King’s
lunched in a large, comfortable, rather clubby dining room, though
the female staff—of any age or degree of distinction whatever—lunched
either in the student hall, or off the premises… The lunching
arrangements at King’s virtually insured that, for women staff,
encounters with their male counterparts were formal and unprofitable,
and that such arrangements existed at all said a good deal, implicitly
about the status assigned to women, not one that could be described
as equal.” Despite such unsatisfactory circumstances in which
Franklin found herself in, Franklin started her work in real earnest.
It may be noted that DNA is a difficult substance to work on; a
sticky, colloidal nucleic acid, its precise properties depend upon
its origin and history. Armed with her rich experience in handling
awkward biological materials, Franklin designed an X-ray camera
suitable for low-angle reflections. She used specimens of DNA which
were drawn into thin fibres under carefully controlled conditions,
notably of hydration. Eventually she did obtain excellent photographic
images of DNA. She was a perfectionist. Franklin (jointly with her
student Ramond G. Goshling) published five papers on DNA during
1953-55. The first two papers were sent for publication in March
1953 even before she came to know about the Watson-Crick model.
The first two papers were published in Acta Crystallographica. These
papers described their observations on the types of X-ray diffraction
patterns given by highly orientated specimen of sodium DNA under
different humidities. They also described the nature of two forms
of DNA (A and B forms) and how they can be prepared. One of these
early two papers reproduced the beautiful X-ray photographs, which
were letter used in analyzing both the forms. The quantitative measurements
on the X-ray pattern of the A form were also described. Franklin’s
third paper on DNA was published in the same issue of Nature (April
25, 1953), which contained the announcement of the Watson-Crick
model of DNA. The fourth paper published in Nature in July 1953
concussively demonstrated that the A form of DNA also contained
two- chain helical structure and though the helical parameters of
the A form were somewhat different but it was essentially the same
type as found in the B form. Unfortunately this important paper
of Franklin was often overlooked. The fifth paper published in Acta
Crystallographica published in 1955 presented an interpretation
of the three dimensional Patterson function of the A form. They
deduced the orientation of the helical molecules in the unit cell.
The Patterson function basically presents the information content
in the X-ray pattern in a generally more useful form for interpretation
in terms of structural models. It does not involve any assumption
and it uses only the observed intensities. This paper also presented
detailed picture of the arrangement of the phosphate groups. Wilkins, who was not at all in good terms with Franklin, welcomed Watson and he even managed to give glimpse of a photograph of Franklin. Commenting on his first impression after seeing the photograph, Watson later commented: “The instant I saw the picture my mouth fell open and my pulse began to race. It was unbelievably simpler than those obtained previously (`A’ form). Moreover, the black cross of reflections which dominate the picture could arise only from helical structure.” He further continued: “Afterwards in the cold, almost unheated train compartment, I sketched on the blank edge of my newspaper what I remembered of the B pattern…By the time I had cycled back to college and climbed over the back gate, I had decided to build two-chain models. Francis would have to agree. Even though he was a physicist, he knew the important biological objects came in pair.” There has been lot of discussion on whether Wilkins was right or not in making available the photograph to Watson without the knowledge of Franklin. Wilkins had his own reasons. Thus in an interview to Sayre, Wilkins told: “ Perhaps I should have asked Rosalind’s permission, and I didn’t. Things were very difficult. Some people have said that I was entirely wrong to do this without her permission, without consulting her, at least, and perhaps I was….If there had been anything like normal situation here, I’d have asked her permission, naturally, though if there had been anything like a normal situation the whole matter of permission wouldn’t have come up…I had this photograph, and there was a helix right on the picture, you could’t miss it. I showed it to Jim (Watson), and I said, “Look, there’s the helix, and that dammed woman just won’t see it.” He picked it up, of course.” For Watson and Crick, Wilkins was not the only source for getting an insight of Franklin’s data. They got the information from the other sources as well. The biophysics committee of the Medical Research Council held a meeting at King’s College in December 1952. In this meeting Randall, who was also a member of the committee, circulated a report on the recent work done in his laboratory at King’s College. This report, alongwith other works, also included a summary of Franklin’s X-ray studies on calf thymus DNA. Max Perutz, Head of the Medical Research Council Unit at the Cavendish Laboratory, was also a member of the committee. In due course, Perutz received a copy of the report., which he handed over to Crick without the knowledge of Franklin. It may be noted that though the report was not marked confidential but then it was not supposed to be a public document. Perutz later wrote: “As far as I can remember, Crick heard about the existence of the report from Wilkins, with whom he had frequent contact, and either he or Watson asked me if they could see it. I realized later that, as a matter of courtesy, I should have asked Randall for permission to show it to Watson and crick, but in 1953 I was inexperienced and casual in administrative matters, and since report was not confidential, I saw no reason for withholding it.” Today Franklin’s photograph of B-form of DNA (now famous as photograph No. 51), which according to one her biographers, `sparked off a scientific revolution’, has become a part of every important book on molecular biology. However, at the beginning she was not given due credit. At the time of giving out the Nobel Prize for thee discovery of the structure of DNA in 1962 Franklin was dead. And Nobel Prize is not given out posthumously. So there is no way of knowing whether she would have got the Nobel Prize or not. There are many scientists, who have not given the Nobel Prize, irrespective of their seminal contribution. What is important is that Franklin’s contributions were ignored. Why? This is again a matter of debate. The fact is that, she was not acknowledged even by such great and sensible scientist like Linus Pauling. To quote Sayre: “That Rosalind missed the Nobel list is no great cause for grief. But what troubles is the other lists she missed. Is it simply because sheer survival has pre-emted claims that an encyclopaedia gives her half a clause in an article on Bernal, simply to call her his pupil, which she was not , or in another half-clause in an article on Wilkins manages to do no more than associate her vaguely with a proudly recorded series of accomplishments….Is it because she failed to live to the age of forty-two that the DNA molecule exhibit in the natural history section of the British Museum omitted Rosalind from the list of people who had contributed to the discovery of the structure until complaints required a change? …And this slow and gentle robbery does not stop. Linus Pauling, certainly a great scientist, and—one would imagine—a careful one, wrote an article for the DNA anniversary issue of Nature in which he, too, hands the credit for the B form photographs of DNA made by Rosalind over to Wilkins, and not once but twice.” In the historic paper of Crick and Watson in Nature
(March 18, 1953) the contributions of Franklin and Wilkins were
limited to a terse statement: “We (Crick and Watson) have
also been stimulated by a knowledge of the general nature of the
unpublished results and ideas of Dr. M.H.F Wilkins, Dr. R.E. Franklin,
and their co-workers at King’s College London.” Watson,
Crick, and Wilkins in their Nobel Lectures cited ninety-eight references
together but none of them referred to Franklin’s work. Wlikins
did mention Franklin’s name in his acknowledgements. It may
be noted that Franklin (jointly with Rammond Goshling) had produced
a draft paper on March 17, 1953, in which she proposed a double
helical structure for DNA. Franklin’s paper did not contain
the crucial idea for base pairing. She also did not realize that
the two chains must run in opposite directions. It may be noted that that everything that was written on Franklin was against her. Aaron Klug , who worked with Franklin made an attempt to put the record straight. In an article in Nature he attempted to put the record straight. Thus at the beginning of this article Klug wrote: “Watson’s account in The Double Helix does not pretend to tell more than one side of the story. The article by Dr. L. D. Hamilton (“DNA: models and Reality”, Nature, May 18, 1968) does no do justice to Franklin’s work. The importance of Franklin’s work has been lost of sight of, partly because of her untimely death. Because, as her last and perhaps closest scientific colleague, I am in a position to fill in the record.” It should be noted that though Franklin reached quite close to solving the structure of DNA and Watson and Crick was helped by her results but in this in no way pre-empt the priority of Watson and Crick or diminish their geniuses. Besides her researches on DNA structure Franklin made important contribution in other fields. As mentioned earlier her work on coal was quite important. She also made important contributions in understanding the structure of viruses. Unhappy at King’s College Franklin moved to Birbeck College, London in 1953, again to work on biological macromolecules but this time not on DNA. She worked on viruses; initially on tobacco mosaic virus. She obtained X-ray photographs superior to any obtained previously and used them to show that the TMV virus is not solid, as had been thought, but a hollow tubular structure. On her work on tobacco mosaic virus J. D. Bernal wrote: “Watson had put forth the hypotheis that the virus structure was…spiral, but one of a different order from that which existed in proteins and deoxyribonucleic acid. Miss Franklin, with the help of very much better X-ray photographs than had hitherto been obtained, was able in essence to verify this hypothesis and to correct it in detail. It was at this point that the extremely fruitful cooperation began between Miss Franklin’s unit and Fraenkel-Conrat at Berkeley, Casper at Yale, and Schamm at Tubingen. Using the method of isomorphous replacement, she showed that the virus particle was not solid, as had previously been thought, but actually a hollow tube…The combined methods of chemical preparation and X-ray examination in the hands of Miss Franklin and her associate was a valuable, and indeed a decisive, weapon in the analysis of these structures.” She had also began working on polio virus. Franklin died on April 16, 1958, at the age of
thirty-seven. Further Reading
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