Rosalind Franklin's Legacy

Within reach

NOVA: How close did Franklin actually come to deciphering the structure of DNA?

Elkin: She was very close. She had all the parameters of the helical backbone. She was the one who figured out that there were two forms of DNA, which made solving the whole structure possible. She had figured out that backbone of the A form is antiparallel. It wouldn't have been very long before she figured out that the B form backbone was antiparallel as well.

The other thing was base-pairing, which was Watson's brilliant idea, made possible by chemical information supplied by Jerry Donohue. But if you look at her notebooks, she was very, very aware of hydrogen bonding. She was very, very aware of the difference between enol and keto forms, which were the key to base-pairing. She was aware of Chargaff's ratios. She was aware of Donohue's work. All the stuff that circled around base-pairing.

How soon might she have worked it out if Watson and Crick hadn't gotten her data?

Well, at one time Crick estimated that it would have taken her three months. I don't know how long it would have taken her, but I think the critical thing with the timing is that she was about to publish her paper on the B form. That's the March 17th draft that Aaron Klug discovered. And that paper was written well before March 17th, and then after the Watson-Crick structure was figured out, she modified it very minimally, and it became the third Nature paper.

"After Watson saw Photo 51, he went out to dinner with Maurice Wilkins and pressed him for the interpretation of it."

There is no way without her data that Watson and Crick could have figured out the structure before [her March 17th draft] got published. Now, if that had gotten published first and then they figured it out—remember, she talked about the double helix in that paper—then even though they had figured out the actual structure, they would have had to incorporate her information and credit her properly, and she would not have been written out of history.

Picture perfect

What did Watson actually get out of Photo 51 beyond the idea that the "X" signified a helix?

After Watson saw Photo 51, he went out to dinner with Wilkins and pressed him for the interpretation of it—the 34-angstrom measurements and so on. At that early date Watson didn't know how to interpret a diffraction photo, other than that an "X" meant helix. In terms of getting measurements out of it, he hadn't the foggiest—at that point. It was Wilkins who told him how to interpret it. [For a closer look at the image, see Anatomy of Photo 51.]

What about the idea that the sugar-phosphate groups were on the outside? Did Watson get that from Photo 51?

No. That was from the MRC report. Watson and Crick got a tremendous amount of information from that MRC report. Now, they persisted in wanting to put the bases on the outside. And it's absurd—you don't put a hydrophobic thing on the outside of a structure in a cell. You put the hydrophobic stuff on the inside where it's protected, and the hydrophilic phosphates and sugars on the outside.

As a chemist Franklin knew that automatically, and so did even a graduate student at King's, Bruce Fraser, when he tried building a model. But Watson and Crick, being weak in their knowledge of chemistry, kept putting it on the outside. And Wilkins said, "You know, Rosalind said it should be on the inside." So Wilkins once again was telling them information that he knew from Rosalind. They kept resisting, however, because to put it on the inside, it seemed very difficult to know how to pack things.

But when Crick saw the MRC report—in which Franklin had not only said that the phosphates are on the outside but had offered measurements of the interphosphate distances—even he couldn't argue with that anymore. So when Watson once again was trying to build a model and it wasn't working, Crick said, "Why don't you put the phosphates on the outside, like Rosalind said?"

Great potential

So the big question is, if Franklin had lived, would she or should she, instead of Wilkins, have received the Nobel Prize with Watson and Crick?

There's a big difference between "would" and "should." Should she have? Absolutely. One of the things I proposed last year at AAAS [the American Association for the Advancement of Science annual meeting] is that I think it should be called the Watson-Crick-Franklin structure. As far as I'm concerned, she was a de facto collaborator. Maybe she didn't give them her information directly. But every time they hit a stumbling point, it was her information that they got from Wilkins that straightened it out. So do I think should she have? Absolutely.

Would she have? I'm not so sure. The Nobel Prize could be very political, and often the Nobel Committee would put great emphasis on those who started the research, which in this case was Wilkins. But even Watson begrudgingly says that she should have gotten it.

"I considered her a genius, and I don't use that word lightly."

Do you believe Franklin had good intuition and that her careful science held her back from making big leaps of imagination, such as might have brought her to the structure of DNA faster than Watson and Crick?

I don't think she had the intuition of someone like Crick or Dorothy Hodgkin, maybe not even of Watson. But she had very good intuition, and she could interpret her own data. She could see things, but unless she could prove them, she wouldn't publish them.

Now, from my point of view, being careful before you publish is a good thing. I've never considered that a liability. I think that's an asset. For someone of her age [Franklin died at age 37], her publication record was phenomenal. It would be phenomenal if she had retired at the age of 75.

You see, what Watson and Crick did was they guessed. They had intuition, their work was brilliant, they guessed. But there were things wrong with the structure they proposed that had to be refined by Wilkins. So it's a double-edged sword. I don't think she had intuition to the level of Crick, but I think very few people in the world ever have had intuition to the level of Crick. Crick and Linus Pauling were in a class by themselves.

Franklin would be 79 now if she had lived. What might she have accomplished in her career? Was she on a trajectory to be a Nobel Prize-winning scientist in her own right?

Oh, sure. I think she would have ended up doing the virus work, probably with Klug, and they probably would have shared a Nobel Prize for that work. That would be the most obvious thing. Lord knows what else she would have done.

If one looks in the records, in all the archives, the way people talked about her was phenomenal. One of the coal researchers wrote a letter about her to Bernal after she died, and in that letter he said, "I considered her a genius, and I don't use that word lightly." She was so young and so brilliant, and she wasn't the kind of person who pooped out. She just gained acceleration and quality in her work as she got older.

Cut short

Do you think her X-ray work contributed to the ovarian cancer that killed her?

I think for sure, though there's no knowing one way or the other. For one thing, she probably had the ovarian cancer gene. I know that there's cancer in the family. But she was also in the X-ray beam a lot. Gosling talked to me about that. When they were physically putting the X-ray diffraction device together, they had practical difficulties. He said he would be lying on the floor holding the apparatus together, and she would spend hours adjusting the specimen. He thought, "Gee, she's in that X-ray beam an awfully long time," because the beam had to be on to do the adjustments.

So is there proof of it? No. Do all X-ray crystallographers end up with cancer? No. I don't think most of them spend as much time aligning the specimen as she did. And she didn't wear lead aprons. It was just beginning to be thought that you ought to do stuff like that.

So did she know that it was potentially dangerous?

It was beginning to be thought that it would be, but I don't think a lot of them took it seriously. I got to know Anne and David Sayre very well. Anne told me an anecdote about how she came to have lunch with David one day, and there was this X-ray source sitting on his desk. Anne was very, very well-read, and she said, "You put that thing in a lead box, or I'm divorcing you tomorrow." David is healthy as a horse today.

At any rate, I know a lot of old crystallographers, so it's not an automatic thing, and it depends on how much you handle the specimen. I think the combination of the specimens and the gene did Rosalind Franklin in.

Glossary

antiparallel: parallel but upside down with respect to each other

base-pairing: In a key insight on the road to discovering DNA's structure, Watson figured out that the four basic chemicals in DNA paired up as follows: adenine with thymine and guanine with cytosine.

John Desmond Bernal: An acclaimed crystallographer, Bernal was head of the physics department at Birkbeck College when Franklin joined the staff in March 1953. It was Bernal who wrote Franklin's obituaries.

Chargaff's ratios: Regarding DNA's base pairs, Erwin Chargaff discovered in 1952 that the total amount of adenine and guanine always equaled the total amount of thymine and cytosine.

coal researchers: Franklin worked on the molecular structure of coal early in her career.

Francis Crick: Co-discoverer, with James Watson, of the structure of DNA.

Jerry Donohue: Chemist sharing an office with Watson and Crick who suggested to Watson that he try modeling DNA with the enol rather than keto forms of the base pairs.

enol and keto forms: The four chemical bases come in two forms, enol and keto, each of which makes an oxygen atom available for bonding in a different position.

Franklin-Wilkins Building: Part of King's College London, where Franklin and Maurice Wilkins worked on the structure of DNA, this is the home of the college's Department of Pharmacy. Opened in 2000, it provides teaching and research facilities for 4,500 students.

Raymond Gosling: A doctoral candidate at King's College London, Gosling assisted Franklin in her X-ray diffraction work.

helical backbone: The basic structure, or scaffolding, of DNA is a double helix.

Dorothy Hodgkin: A crystallographer, Hodgkin won the Nobel Prize in chemistry in 1964.

hydrogen bonding: DNA's four chemical bases are bonded together by hydrogen atoms.

Aaron Klug: Chemist who collaborated with Franklin on her virus work in the mid-1950s. Klug received the Nobel Prize in chemistry in 1982.

March 17th draft: Written in March, 1953, by Franklin, this paper summarized Franklin's findings about the double-helix backbone in the B form of DNA. It was published alongside Watson and Crick's famous paper in the April 25th, 1953, issue of Nature.

MRC report: Franklin's portion of a 1952 Medical Research Council report inspired Watson and Crick to cease trying to put the bases on the outside of their burgeoning model of DNA.

Linus Pauling: The foremost chemist of his day, Pauling was trying to determine the structure of DNA at the same time as Watson and Crick. Pauling is the only person to ever win two Nobel Prizes—chemistry in 1954 and peace in 1962.

Anne and David Sayre: Anne Sayre published a biography of her good friend Franklin in 1975 (Rosalind Franklin and DNA, Norton). David Sayre, her husband, is a crystallographer.

sugar-phosphate groups: DNA's backbone is made up of sugar-phosphate groups to which the four bases adhere and point toward the helical axis.

34-angstrom measurements: Crystallographer William Astbury determined that DNA's base pairs lay flat, 3.4 angstroms apart, and that the distance between each turn of the helix is 34 angstroms.

two forms of DNA: Franklin discovered that DNA comes in two forms, which she labeled "A" and "B."

James Watson: Co-discoverer, with Francis Crick, of the structure of DNA.

Maurice Wilkins: A physicist at King's College London who was Franklin's immediate boss when she worked there. Wilkins shared the Nobel Prize in physiology or medicine with Watson and Crick in 1962.

X-ray work: Franklin used X-ray diffraction techniques to study the structure of DNA.