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.
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.
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:
- 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.
- 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!
- 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.
- 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!