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Musings of a Cancer Doctor
Wide-ranging views and perspective from George W. Sledge, Jr., MD
Thursday, July 31, 2014
The Also-Rans

Recently, in preparation for a lecture I gave on writing scientific papers, I had the opportunity to re-read Watson and Crick’s original 1953 Nature paper, “Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid.” It is not just the most important scientific paper in biology written in the last century, it is also one of the most beautifully written: concise, clear, jargon-free, and with the greatest punch line for any paper in the scientific literature: “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” Try and top that for a discussion section.

 

I downloaded the paper from the Nature website, which required me to go to the actual April 25, 1953 issue. My eyes wandered for a few seconds over the table of contents for the issue, and suddenly I had a thought: I wonder what it was like to publish a paper in that issue of Nature if your name wasn’t Watson or Crick? To be remembered, forever in the annals of science, as one of the also-rans.

 

There are many equivalents, both inside and outside science: giving a talk at the Linnaean Society in 1858 in the same session where Darwin and Wallace’s first papers on evolution were presented. Or, perhaps, being the back-up act on the 1964 Ed Sullivan Show for the Beatles. A wonderful trivia question, by the way: Las Vegas entertainers Allen & Rossi, and the impressionist Frank Gorshin, in case you want to wow someone at a dinner party.

 

6 Articles, 23 Letters

So who were the also-rans? There were six articles and 23 letters in the issue. Of the six articles, three were about the structure of DNA. In addition to the Watson and Crick article, there was Maurice Wilkins’ “Molecular Structure of Nucleic Acids: Molecular Structure of Deoxypentose Nucleic Acids” and Rosalind Franklin’s “Molecular Configuration in Sodium Thymonucleate.”

Franklin’s paper includes the beautiful x-ray crystallography that has become a commonplace for biology texts ever since, a ghostly X of salmon DNA.

 

The Wilkins and Franklin papers represented important support to the Watson-Crick modeling paper, which is why the two Cambridge researchers had encouraged their King’s College colleagues to submit papers at the same time.

 

The interaction of Watson and Crick with Wilkins and Franklin (both of King’s College. London), and for that matter the fraught relationship of Wilkins and Franklin, are part of the lore of molecular biology. Watson and Crick ran no experiments, relying instead on the work of others, most prominently Rosalind Franklin’s X-ray diffraction studies of DNA, which they correctly interpreted as evidence in favor of a double helix. It was a crucial piece of experimental data, and one that both Wilkins and Franklin had misinterpreted. Watson’s classic memoir, The Double Helix, describes the interactions in picturesque detail, and his description of Franklin in particular struck many then and later as both petty and sexist.

 

The Nobel Prize can be given out to a maximum of three investigators, and in 1962 Wilkins was investigator number three. Franklin had, in the intervening years, developed ovarian cancer, and died at the age of 37, some four years before the prize was awarded. She spent some of her final months with Crick and his wife, receiving chemotherapy. The oncologist in me has always wondered whether the Jewish Franklin carried an Ashkenazi BRCA mutation.

 

Would she have been awardee number three had she lived? This is an unanswerable question, but her premature death doomed her to permanent also-ran status, making her a feminist icon in the process. Could she have come up with the double helix structure on her own, given sufficient time? Perhaps. But her Nature article concludes with a sad, might-have-been-but-wasn’t, admission: “Thus our general ideas are not inconsistent with the model proposed by Watson and Crick in the preceding communication.” Not inconsistent with: a grudging admission that she had failed to see what her own data supported.

 

Impact Factor

Editors of scientific journals, and contributors to those journals, scrutinize the impact factor. The impact factor is quite simple: add up the total number of citations for a journal in the first two years after publication, and divide by the number of citable items (usually articles and reviews). The best journals (Science, Nature, Lancet, New England Journal of Medicine) usually have the highest impact factors.  The vast remainder are decidedly mediocre: a sea of journals with an impact factor of 2 or thereabouts. Most published science is unmemorable, rapidly forgotten even by the authors. Citations do not have a Gaussian distribution; instead they follow a power law distribution, with a few 900-pound gorillas followed by a long tail. And seldom has the power law been so severe as that issue of Nature.

 

Impact factor is a way of keeping score, though not without its own issues. One problem with it is that it cannot measure the long-term impact of a paper. With 60-plus years of follow-up, however, we can look at the long-term impact of the work published in that April 25, 1953 issue of Nature. Watson and Crick are the huge winners, of course: Google Scholar says their paper has been cited 9866 times, and we hardly need the citation numbers to realize the revolutionary importance of that paper. The Wilkins and Franklin papers clock in at 618 and 833 citations, marking them as important contributions. But what of the others?

 

Let’s begin with the other three articles. They are, in order of presentation, “Refractometry of Living Cells”; “Microsomal Particles of Normal Cow's Milk”; and “Measurement of Wind Currents in the Sea by the Method of Towed Electrodes.” None is particularly remembered today, I think it is safe to say. Google Scholar reports the three articles as having had, respectively, 172, 41, and 15 citations. OK citation numbers, even today, but definitely in the also-ran category. Interestingly, the refractometry paper was cited by a 1991 Science paper on optical adherence tomography that itself has been cited 8400 times.

 

Letters

The letters range from 0 to 235 citations, according to Google Scholar. The most recognized is W.R. Davis’s “An Unusual Form of Carbon”, which has been cited 235 times, most recently in 2010. The story here is interesting. Davis and his colleagues worked at the British Ceramic Research Association in Stoke on Trent in England, where they studied the carbon deposited on the brickwork of blast furnaces. They identified what they described as tiny “carbon vermicules,” some as small as 100 angstroms. In retrospect (hence the 235 citations) they were early discoverers of carbon nanotubes, members of the fullerene structural family, now actively studied for their fascinating physicochemical properties. Three researchers received Nobel prizes in the 1996 for fullerene studies, so one can feel for Davis and his fellow Stoke on Trent ceramicists. They were dual also-rans, publishing in the same issue as Watson and Crick, and coming along a few decades too early in the as-yet-unnamed fullerene field.

 

Of the other papers published as letters, what is there to say? I love the title of K.A. Alim’s “Longevity and Production in the Buffalo,” though R. Hadek’s “Mucin Secretion in the Ewe's Oviduct” runs a close second for my affections.

 

But is easy to understand why such articles are poorly cited and long forgotten, given the relative obscurity of the topics. One of the keys to success in science is choosing the right problem to work on, and mucin secretion in the ewe’s oviduct probably cannot compete with decoding the key to life on earth.

 

Least Cited, But...

The least cited paper (I could not find any citations using Google Scholar) is my favorite: Monica Taylor’s “Murex From the Red Sea”. Taylor wrote from Notre Dame College in Glasgow, where she curated a natural history collection. Sir John Graham Kerr had collected some 300 Murex tribulus shells from the Great Bitter Lake in Egypt. Murex was what would now be called an alien invasive species, introduced following the completion of the Suez Canal, and Sir John (would a 2014 letter to Nature ever refer to a Sir John?) and Monica wondered whether the species had altered its presentation, “relieved of the shackles of environment.” The letter was a plea for specimens from the Red Sea so that the comparison might be made. Wikipedia informs me that Murex tribulus is a large predatory sea snail, with a distribution from the Central Indian Ocean to the Western Pacific Ocean.

 

Did Monica Taylor ever get her Red Sea specimens? Life is full of small mysteries. Taylor herself is a fascinating soul. Born in 1877, the daughter of a science teacher and the cousin of Sir Hugh Taylor, one-time Dean of the Princeton Graduate School, she trained as a teacher prior to becoming a nun. So Monica Taylor was actually Sister Monica, and Sister Monica dearly wanted to become a scientist. But the road was not smooth for a woman, let alone a nun, wishing to be a scientist in the early twentieth century. She was refused permission to attend the University of Glasgow, and was unable to complete an external degree from the University of London due to Notre Dame’s inadequate laboratory facilities.

 

After several thwarted attempts, according to the University of Glasgow website, “She was eventually granted permission to do laboratory work in the Zoology Department of the University of Glasgow, provided she did not attend lectures and was chaperoned by another Sister at all times.” There she impressed Professor Graham Kerr, who encouraged her to pursue an advanced degree, and obtained permission for her to attend classes. After receiving a DSc from the University of Glasgow in 1917, she headed the Science Department at Notre Dame College until her retirement in 1946, all the while conducting significant research in amoebic zoology.

 

In 1953, the year of her Murex letter, she was awarded an honorary doctorate from the University of Glasgow for being "a protozoologist of international distinction." She died in 1968; six years after Watson and Crick got their Nobel prizes. No citations, and no Nobel, but perhaps you will remember this also-ran, a woman of courage and fortitude.

 

Most of us are also-rans, if judged against those carved into science’s Mount Rushmore. Glory would not be glorious if it was common. But maybe we have it wrong if we think the also-rans felt demeaned by their also-ranness. Maybe Dr. Alim or Dr. Hadek or Sister Dr. Taylor enjoyed their brush with greatness. And maybe, just maybe, they were satisfied with lives well lived in service to science and mankind.

About the Author

George W. Sledge, Jr., MD
GEORGE W. SLEDGE, JR., MD, is Chief of Oncology at Stanford University. His OT writing was recognized with an APEX Award for Publication Excellence in the category of “Regular Departments & Columns.”