April 2014 – Mozart of Molecular Biology


Vol. 43, No. 2, April 2014
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The “Mozart of Molecular Biology” and Session Mates at the HSS 2013 Annual Meeting

by Pnina G. Abir-Am, Brandeis University

The “Mozart of Molecular Biology,” as Matthew S. Meselson is known, evoking the many crucial experiments he was part of, (by analogy with W.A. Mozart’s many musical compositions, in both cases at a young age), was the star of our session at the 2013 HSS annual meeting: “DNA at 60: (2013, 1953) New Sources, New Questions, New Historiographies.” One of the new points that the session attempted to convey was that DNA’s structure, whose 60th anniversary prompted the session, had begun to be digested by the scientific community only after the Meselson-Stahl experiment proved how DNA replicates,1 (semi-conservatively) five years later in 1958. Therefore, 2013 marked not only the 60th anniversary of the better known discovery of DNA’s structure, by now a cultural icon, but also the 55th anniversary of the less well-known Meselson-Stahl experiment, called by many, including a former HSS President, “the most beautiful experiment in biology.” 2

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Article: The “Mozart of Molecular Biology” and Session mates at the HSS 2013 Annual Meeting
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However, Meselson is not only eponimically famous for his role in devising the new method of density gradient for distinguishing between isotopes of nitrogen attached to DNA bases in successive generations of bacteria, which proved that DNA replicates semi-conservatively. He is also well known as a leading analyst and adviser on biological and chemical weapons, whose views influenced the U.S. government’s decisions to sign international conventions for banning both types of weapons.

In addition to his roles as scientist and policy adviser, Meselson further took the brave stance of a public intellectual when he successfully contested official claims by both Superpowers with regard to their, or their enemies’, production or use of toxins as weapons. In the 1980s he proved that the “yellow rain” in Indochina, alleged by the U.S. to reflect the use of toxins on civilians by its enemies, were actually synchronized droppings of wild bees.3 In the early 1990s, Meselson and six colleagues investigated the Soviet Union’s claims that an anthrax outbreak stemmed from contaminated cow feed, eventually concluding that the outbreak resulted from an accident in a facility for biological weapons.4

We were, thus, very fortunate to have Meselson among us as a speaker to provide a personal retrospective on the landmark experiment on DNA replication. Though Meselson proved to be a great raconteur, with a distinct sense of humor, who repeatedly elbowed those who wished to shake his hand on public health grounds, (a consciousness he apparently acquired during a recent trip to Asia which endowed him with a persisting cold; that cold further required that he be supplied with hot tea, a demand that the head of the HSS staff was kind enough to meet). His cold, coupled with trouble with the microphone, meant that his voice did not project homogeneously, and I suspect that his most interesting remarks were likely missed by many members of the audience. This is why it would be useful to draw lessons here from Meselson’s remarks, as well as the session he was part of, for the benefit of our remarkably interactive audience, as well as those who missed the session of the molecular biological Mozart for other reasons.

Meselson began by responding impromptu to questions I had sent to him two months earlier, in my capacity as session organizer and author of his, his collaborator, and their joint experiment’s entries in the electronic Encyclopedia of Life Sciences.5 Though he did not cover all the names of the old guard in whose views I was interested, he confirmed that his mentors at Caltech, his Ph.D. adviser Linus Pauling, the Chair of the Chemistry Division, as well as the Chair of the Biology Division, George W. Beadle, and Max Delbruck, the guru of the Phage Group, were supportive, each in his own way. Indeed, the immediate favorable reception of the Meselson-Stahl experiment in 1958 contrasted with the indifference encountered by the DNA structure in 1953. Though Meselson has developed an interest in the history of science he still attributes the good reception he encountered at the time to the experiment’s correctness and beauty. Could it be that his mentors may have had additional motives in sponsoring a three-year-long experiment, which further encountered two years of setbacks? Nor does Meselson suspect any “foul play” when he was asked why his experiment with Stahl became mainly known as a boost for DNA structure, instead of being evaluated for its unique ingenuity.

As to the question why those others who were much concerned with the problem of genetic replication (e.g. Crick, Delbruck, Doty, Levinthal, Schachman, Stent, Watson) did not come up with the Meselson-Stahl experiment, Meselson was too modest to say that they were not smart enough or that they did not have a perfect collaborator, as he did. He implied however that tools he learned from Pauling were crucial. Meselson’s single mindededness was equally crucial in overcoming Pauling’s lack of interest in DNA, or his demand that Meselson complete a Ph.D. thesis on an unrelated topic, of no interest to Meselson, which Meselson never published to Pauling’s chagrin. Pauling’s demand delayed the experiment on DNA replication for several years.

Last but not least, on the question of what was it at Harvard, where Meselson arrived in 1961, that propelled him toward a long-term involvement with science policy on biological and chemical weapons, (having served as an analyst and adviser for the administrations of Presidents Kennedy, Johnson, Nixon, Ford, Carter, and Reagan) Meselson mentioned the Vietnam War, his friendship with Henry Kissinger, and the influence of other activist molecular biologists there such as Paul Doty and John Edsall. It was particularly gratifying when a member of the audience posed a question on the relevance of Meselson’s science policy activities in the present, when chemical weapons continue to be a source of concern, as in the recent crisis in Syria. Such a question would have signaled to Meselson, who had been accused by (science) students that he cared more for science policy than for their future in science, that historians of science have a wider perspective and consider science policy to be of equal importance.

Meselson’s talk was perfectly introduced by the preceding speaker, William Summers of Yale University, whose talk “Not Quite a ‘Eureka Moment’: Reception of the DNA Structure by the American Phage Group” included the Meselson-Stahl experiment as a landmark in the history of molecular biology, (taught by Summers to many generations of science students) while pointing to Meselson in the first row. Summers argued, with the help of documentation from his recent archival study of the Personal Papers of Gunther Stent at the Bancroft Library in Berkeley, California, that at the time the reception of the discovery of DNA structure was slow and far from enthusiastic. Summers’ findings, as he himself emphasized, contrast with the views expressed by scientists at the 50th anniversary of the discovery of DNA structure in 2003, according to which they immediately grasped the significance of that discovery.

This was an important point because the session revolved around the contrast between “history” and “memory,” while also highlighting how anniversaries help create collective memories that reflect social and political interests in the present. Summers, who also chaired the session, created a seamless transition to Meselson’s talk not only by mentioning two of Meselson’s famous experiments (the other one being the isolation of m-RNA on which Meselson collaborated with Sydney Brenner, a 2002 Nobel co-laureate, and François Jacob, a 1965 Nobel co-laureate) in his talk, but also by posing questions to Meselson, as well as to the other speakers.

Miguel Garcia-Sancho of the University of Edinburgh contrasted the well-known preoccupation with DNA structure with a parallel, and currently hot, topic of DNA sequencing, in his talk, “Narratives, Disciplines, and the Agency of Biomolecular Techniques: Or why Frederick Sanger shifted from protein to nucleic acid sequencing (1945-1977)” based on findings from his recent book.6 Garcia-Sancho emphasized that DNA sequencing began as an offshoot of protein sequencing, a fact often missed by practicing DNA sequencers, yet one perfectly illustrated by Sanger’s career. Pursued in the 1940s and 1950s in the Department of Biochemistry at the University of Cambridge, U.K., and after 1962 in the Medical Research Council’s Laboratory of Molecular Biology, (MRC-LMB) Sanger’s career shifted smoothly from protein to DNA sequencing.

Sanger received a Nobel Prize within four years of each discovery: in 1958 for protein sequencing and in 1980 for DNA sequencing, the latter shared with U.S. molecular biologist Wally Gilbert. Garcia-Sancho interrogated Sanger’s shift by suggesting that sequencing was a “form of work” that suited Sanger’s outlook on science, while further refuting previous suggestions that Sanger shifted to DNA sequencing as a result of influence by Crick and Brenner, his would-be colleagues at the MRC-LMB. Garcia-Sancho also replied to a number of questions from the audience on SchrÖdinger’s and Crick’s respective ideas on the genetic code, as well as on how the conflation between information as sequence and information as code is affecting current New Generation Sequencing and systems biology.

Pnina G. Abir-Am’s talk “Why does the identity of the discoverers of DNA structure keep on changing” focused on some reasons for shifts in the publicly advocated number of discoverers, from two in 1953, to three in 1962, and four in 2003. Based on her forthcoming book DNA at 60, 50, 40, 21: History, Memory, and Cold War Legacies in Scientific Discovery, which she hoped would be ready in page-proof form for the HSS Meeting were it not for a major surgery7 (with a happy ending but lost time). Abir-Am argues that a spectrum of new sources, both primary and secondary, completely changes our understanding of this discovery, an understanding totally dominated by the endlessly advertised perspective of the so-called “winners.” Rather than being seen as the “rag to riches” story of two junior collaborators, (Crick and Watson) the talk suggested that those two were mere pawns in much larger games, pursued by several lab directors. The talk further argued that the latter’s power, interests and rivalries determined who would be publicly accepted as a discoverer. She also highlighted the key role of class, race, and gender bias prevailing at the time, which led to a minimalist designation of discoverers in 1953, (and a more inclusive one in 2003) while reminding the audience that the careers of all DNA scientists, not just Rosalind Franklin’s, were affected by the then prevailing societal biases on gender, race, but especially class.

Abir-Am concluded that neither the minimalist designation of two discoverers, nor the inclusive one of four, match the historical record, which has greatly expanded in the last decade. She also replied to several questions. Most revealed captivity to the “received view” according to which the discovery of DNA structure remains conflated with those who became most associated with it, without interrogating how such associations were socially constructed, or why they no longer match the newly available historical record. In this sense, the session was useful in confirming the urgent need for her forthcoming book, which hopes to put the “received view” to a much needed final rest.

This session included members of the audience who also attended the session “DNA at 50” organized by Abir-Am and Summers for the HSS Annual Meeting in 2003, which also included a panel composed of leading local DNA scientists (the 2003 Meeting was also held in Boston) Paul Doty, (deceased in 2011) Alex Rich, (MIT) and Wally Gilbert (Harvard, Biogen and Brickbottom Art Collective). It drew a good crowd but was difficult to duplicate ten years later for obvious reasons. Abir-Am wishes to thank HSS and its program organizers for the foresight to schedule the Annual Meeting in time for her to recover. She is also grateful for the unexpected opportunity the session gave to her to feel fully recovered, when a provocative question required a forceful reply, one she could not have delivered in the preceding two months.

1. ^ Meselson, M. and F.W. Stahl (1958) “The Replication of DNA in Escherichia coli,” PNAS, 44: 671-682

2. ^ Holmes, F.L. (2001) Meselson, Stahl, and the Replication of DNA, A History of “The Most Beautiful Experiment in Biology,” New Haven, CT.: Yale University Press.

3. ^ Bass, A.B. (1986) “One Scientist’s Crusade, A Portrait of Matthew Meselson,”Technology Review, April, 40-54.

4. ^ Meselson, M. et al., (1994) “The Sverdlovsk Anthrax Outbreak of 1979,” Science, 266, 1202-1208.

5. ^ www.els.net, see entries A25056; (on Meselson) A25057; (on his collaborator Franklin Stahl) and A25093; (on the Meselson-Stahl experiment) all submitted in the summer/ early fall of 2013.

6. ^ Miguel Garcia-Sancho, Biology, Computing, and the History of Molecular Sequencing; From Proteins to DNA, 1945-2000. (London: Palgrave McMillan, 2012)

7. ^ “My Medical Tsunami: Lessons from a Rare Patient’s Recent Ordeal in Two Boston Hospitals,” 22pp. (copies available upon request). This is part of a forthcoming collection on medical ordeals from the patient’s perspective. Those who wish to interrogate their own medical ordeal/s are very welcome to join by sending a draft. Guidelines for revision will be sent shortly after.