Thursday, October 07, 2010

The Velvet Underground of Molecular Biology

The Velvet Underground was a New York rock band in the 1960s. It was never very popular and never made much money but it's said to have influenced many other, more successful, bands.

Chad Orzel asks you to identify The Velvet Underground of Science by which he means an individual who isn't very famous but had a huge impact on science. Naturally, he has an example from physics.

I have an example from molecular biology. Max Delbrück (1906-1981) was one of the founders of the 'phage school (along with Salvador Luria). Delbrück began his science career as a physicist but when he went to the USA he switched to biology and soon became interested in bacteria and bacteriophage.1 During the 40s, 50s, and 60s he had a huge influence on the members of the 'phage group who used to meet regularly at Cold Spring Harbor where Delbrück taught a summer course in 'phage genetics.

Jim Watson, Matt Meselson, Franklin Stahl, Gunther Stent, Seymour Benzer, Edward Kellenberger, and Alfred Hershey are just a few of the scientists who were directly influenced by Delbrück. They all got together to contribute to Phage and the Origins of Molecular Biology in 1966. The book was a Festschrift in honor of Max Delbrück on his 60th birthday.

There were many more second and third generation scientists who grew up in the 'phage group. My own supervisor used to refer frequently to Delbrück's "Principle of Limited Sloppiness" as an effective way of doing science.

Delbrück, Alfred D. Hershey, and Luria won the Nobel Prize in 1969 but he (Delbrück) is still not very well known among today's students. I think that every biochemistry and molecular biology student should have to read The Eighth Day of Creation by Horace Freeland Judson in order to learn the history of their field.

They might discover that much of what they think of as "modern" was actually understood almost half a century ago.

Photo Credits: Top: Delbrück in the early 1940s from Wikipedia. Bottom: Delbrück and Luria at Cold Spring Harbor in 1953.

1. Physics was too easy—he wanted more of a challenge.


  1. an individual who isn't very famous

    Nobel winner isn't very famous? OK. In the category not very famous but very influential I'd nominate, if we are talking the beginnings of the molecular biology, George Gamow and Nikolaj Timofeev-Ressovsky.

  2. Delbruck and Luria both also factor in Matt Ridley's nice, short book on the life of Francis Crick.

  3. I STRONGLY second the recommendation for Judson's book. It's a classic.

    I nominate Reiji Okazaki, who died long before his time (of leukemia more than likely induced by radiation exposure from the Hiroshima bomb when he was a teenager) and only a few years after the discovery of semidiscontinuous DNA replication that made him immortal.

  4. And perhaps I can bend the rules a bit and nominate a guy who was purely a classical geneticist but whose work led to a feast of molecular biology: Ed Lewis, discoverer of homeotic mutations in Drosophila.

  5. As an undergraduate at Caltech, I got used to seeing Delbrück zipping about the campus on his bicycle. Since he was one of the local Nobel laureates, I thought of him as fabulously famous. It's funny to see his name pop up in this "Velvet Underground" context.

  6. I nominate Michael Behe and Jonathan Wells as the 'Milli Vanilli' of molecular biology.

  7. Obviously Erwin Schrodinger is very famous, and many people are aware of his book What is Life, but hardly anyone today has probably read it. He made a prediction of physical gene size based on irradiation mutation rates and known physical chemical properties which is not too bad considering that DNA was not known to be relevant at that time. So many years later it's hard to known how influential his book really was on early molecular biologists (like Delbruck) but my impression is that it was significant.

  8. This comment has been removed by the author.

  9. @ anonymous

    Schrödinger was clearly influenced by the ground-breaking paper in which Delbrück, Zimmer and Timofeeff concluded from radiation experiments that genes
    have a defined molecular structure, as well as a precise
    location (Timofeeff-Ressovky, N. W., K. G. Zimmer, and M. Delbrück Über die Natur der Genmutation und der Genstruktur, Nachrichten von der Gesellschaft der Wissenschaften zu Göttingen: Mathematische-Physikalische Klasse, Fachgruppe VI, Biologie Bd. 1, Nr. 13, 189-245). A scanned copy of this paper can be found at:

    The impact of this paper has been described as The target hypothesis as a "quantum leap" to gene mutations (Luft FC (1999):J Mol Med 77(12):813-815)

  10. I won't exactly call Delbruck the Velvet Underground since he was pretty well known and won a Nobel Prize.

    I think there's two kinds of Velvet Undergrounds, ones whose achievements were recognized by their peers when they were alive but which did not make their names publicly known, and others whose achievements did not even become known to their peers until after they died.

    In the first category:
    Bruno Zimm for crystallography
    Norman Heatley for penicillin
    Stanislaw Ulam for math
    Carl Woese for microbiology
    Robert Wilson for physics

    In the second category:
    Josiah Willard Gibbs for thermodynamics
    Gregor Mendel for genetics
    Ludwig Boltzmann (partially)
    George Price for evolutionary biology
    Henrietta Swan Levitt for astronomy
    Hugh Everett for quantum theory

  11. round-breaking paper in which Delbrück, Zimmer and Timofeeff concluded from radiation experiments that genes have a defined molecular structure

    Supposedly this series of experiments was Timofeev-Ressovsky's idea. And of course the core of it was simply a replica of Rutherford's experiment.

  12. Two candidates:

    Molecular Genetics: Francis Ryan who did a lot to clarify evolution through studying recombination and mutagenesis in Neurospora. Among other things he got Joshua Lederberg interested in recombination. He also wrote (with Ruth Sager), the first textbook of cell biology - Larry would appreciate that. He died in 1963, at a fairly young age.

    Biophysical chemistry: Jerome Vinograd, who did so much to understand the chemistry of the double helix. He invented density gradient centrifugation, which led to the Meselson-Stahl experiment among others. He also discovered supercoiled DNA - which led to plasmids, and cloning.

  13. Larry, how about Oswald Avery? Chargaff and Lederberg explicitly state that the work from his lab deeply influenced the direction of their research.

    Also his work was what ultimately influenced the phage group to take DNA as a serious contender for the molecular basis of heredity.