Merry Xmas from Oswald Avery – but what if he had died early?

by Matthew Cobb

Here’s a picture of Oswald Avery (1877-1955), at an Xmas party in his Rockefeller Institute lab, in 1940. Avery – you may not have heard of him – was the man who discovered that genes are made of DNA, in a paper published in January 1944.

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Photo from this excellent NIH site: https://profiles.nlm.nih.gov/CC/

Avery was proposed for the Nobel Prize dozens of times, both for his main work on pneumonia, and then for his truly ground-breaking discovery about DNA’s role as the ‘transforming principle’ in Pneumococcus bacteria.

At the time Avery was working, everyone thought that genes were made of proteins. Avery’s discovery was like a thunderbolt, and for that reason many people refused to accept it for many years. DNA was thought to be ‘boring’, composed of four bases – A, C, T and G – in roughly equal proportions. Proteins, on the other hand, were rich and varied, just like genes. Chromosomes are made up of DNA and proteins, and the assumption was that DNA was the backbone while the genes were made of proteins.

Jerry has written about Avery’s astonishing contribution before on this site, and I’ve written pieces for The Guardian and, at greater length, at Current Biology as well as in my book.

But what if Avery wasn’t able to do this work? What if he had died before identifying the genetic material as DNA? How would we have discovered what genes are made of? This example of counter-factual history is the subject of an article I’ve just published at PLoS Biology. It’s open access, so anyone can read it. Rather than repeating the whole thing, I’ll just give you an idea of the approaches I took, and I’d encourage you to go over, read the article, then comment on it here.

It seems to me that there are four major alternative routes to discovering the role of DNA in a world that was cruelly deprived of Oswald Avery’s perspicacity, determination and genius:

  1. Someone else would simply have done Avery’s work. The problem is, the system he was studying – transformation in Pneumococcus – is pretty niche. In reality, no one else who knew about transformation tried to identify its material basis, so it is hard to imagine that history would have simply proceeded along the same path, but with someone else’s name replacing Avery’s in the history books.
  2. An attempt might have been made to prove the role of proteins, for example in virus replication, and the result would have been that, in fact, DNA played the hereditary role. However, that study had already been done, by Wendell Stanley, in 1936, and he found that protein was the genetic material (in fact there were small amounts of nucleic acids in his sample). So sure was the world that Stanley’s result was correct, he got the Nobel Prize for this mistaken discovery in 1946!
  3. Perhaps studies of DNA structure would have led to the recognition that, as Watson and Crick put it in their second Nature paper of 1953, ‘the precise sequence of the bases is the code which carries the genetical information’, and that therefore DNA could be as varied as proteins. However, although researchers such as William Astbury were making X-ray crystallography studies of DNA even before the war, there was no way of identifying the sequence of DNA bases until the 1970s. It is even possible that the double helix could have been discovered, fêted for its role in chromosome replication (the reciprocal pairing of bases explains that), without its genetic role being suspected.
  4. It is even possible that people studying protein synthesis might have studied the role of RNA in protein synthesis and then worked out that the information must have got into the RNA from somewhere, and that a DNA-based gene would be the most likely explanation.

The aim of the article is not particularly serious – it is supposed to be provocative and amusing, an Xmas entertainment, much like my article here about ‘what if Franklin and Wilkins had been able to work together?’ (The Avery piece is also the article I referred to in the third para of that post…)

I hope that those of you who know something about the science of the period will be stimulated, and those of you who don’t will be informed. Merry Xmas one and all!

Reference: Cobb M (2016) A Speculative History of DNA: What If Oswald Avery Had Died in 1934? PLoS Biol 14(12): e2001197

16 Comments

  1. Kevin
    Posted December 23, 2016 at 10:54 am | Permalink

    Time would have unfolded the science. In a textbook of today it would feel about the same, but the history of discoveries would be different.

    Physicists have long pondered this question about Einstein’s General Relativity. Although, not as esoteric as Avery’s approach, Einstein’s synthesis of conceptualizing gravity would have probably happened in less than ten to fifty years after if he had not done it.

  2. GBJames
    Posted December 23, 2016 at 11:04 am | Permalink

    sub

  3. Posted December 23, 2016 at 11:48 am | Permalink

    Poor Wendell Stanley! He must have felt badly when his most important results were shown to be untrue.

  4. ThyroidPlanet
    Posted December 23, 2016 at 12:15 pm | Permalink

    The story of and around DNA gets better with time – so thrilling to hear more stories and ideas like this. Same goes for e.g. myoglobin structure. A sign I’m getting old perhaps.

    But I think someone should start a retro-Nobel prize to honor people like Avery, Franklin, and others who were denied.

    Thanks for this nice little article.

    • Filippo
      Posted December 23, 2016 at 2:57 pm | Permalink

      “But I think someone should start a retro-Nobel prize to honor people like Avery, Franklin, and others who were denied.”

      Concur. Let’s just decide that that is so. Does one ipso facto really need munitions manufacturer Alfred Nobel’s approbation to validate the efficacy Avery’s, Franklin’s, etc. efforts?

      Cheers!

      • ThyroidPlanet
        Posted December 23, 2016 at 3:05 pm | Permalink

        It’d have to be yet another prize, in practical terms, and I used the editorial “someone should …” meaning, not me. I’d like to, but you know…

      • Diane G.
        Posted December 23, 2016 at 10:34 pm | Permalink

        “Does one ipso facto really need munitions manufacturer Alfred Nobel’s approbation to validate the efficacy Avery’s, Franklin’s, etc. efforts?”

        The answer, obviously, is no, as it is to another question: would there need to be an associated monetary award?

        So it’s only about honoring the true discoverers of salient advances in science. Seems to me there’d be enough prestigious scientists interested in pursuing this; maybe present a proposal to the AAAS & its European equivalent(s) and I bet it’d be well received.

  5. Gregory Kusnick
    Posted December 23, 2016 at 12:46 pm | Permalink

    I like the protein synthesis route. If people were convinced that protein was the genetic material, naturally they would want to know how it gets replicated. Elucidating that process leads unavoidably to the realization that the information determining protein structure ultimately resides in DNA (though it might have taken decades to get there).

  6. Michael Fisher
    Posted December 23, 2016 at 2:10 pm | Permalink

    Merry Christmas Matthew!

  7. Mark Sturtevant
    Posted December 23, 2016 at 3:02 pm | Permalink

    Well, the classical experiment was done by Avery, MacLeod, and McCarty, although I understand that Avery was the more important of the 3. Still, might not have Colin MacLeod and Maclyn McCarty been able to extend Frederick Griffiths’ experiments in some fashion?
    Also, there is the Hershey and Chase experiment that followed, showing the bacteriophage injects DNA into E. coli to convert them into virus factories. That would have gone forward, I expect.

    • Posted December 23, 2016 at 3:27 pm | Permalink

      If you read the article (highly recommended!) you’ll see the problem with both your suggestions. To summarise briefly: MacLeod and McCarty were both medics looking for projects to work on. Without Avery, they wouldn’t have taken the work forward. Hershey and Chase a) didn’t show that DNA was the genetic material (despite what the textbooks say), and Hershey didn’t claim it did; b) they only did the experiment because of Avery’s work, which Hershey followed closely… – MC

      • Mark Sturtevant
        Posted December 23, 2016 at 6:14 pm | Permalink

        I see! Thank you.

  8. Merilee
    Posted December 23, 2016 at 7:07 pm | Permalink

    Sub

  9. Posted December 23, 2016 at 9:45 pm | Permalink

    I recently finished “I Contain Multitudes” by Ed Yong. Generally pretty good, but I think he is a bit over the top about the frequency of horizontal gene transfer (using Avery’s experiments as a prime example), and he even seems to go so far as to imply that bacteria actively seek out and incorporate genetic capabilities that would be useful. My take is that horizontal transfers are significant on an evolutionary time scale, but not rampant on an ongoing basis. Otherwise, there would not be underlying conserved sequences that even allow horizontal transfers to be recognized – there would simply be no recognizable lineages.

  10. Diane G.
    Posted December 23, 2016 at 10:39 pm | Permalink

    Thanks for the intriguing present (as in Christmas present), Matthew! Way beyond me but I’m enjoying the discussions between those who know a lot more about it than I do.

  11. Posted December 24, 2016 at 3:58 pm | Permalink

    Great paper! Likewise the picture of Avery by the tree. Has he got a cupful of DNA?


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