The Nobel Laureate That Wasn’t

As much as I take notice of the Nobel prizes from time to time, they are far from any kind of perfect system for delineating and recognising the most important research and researchers in the sciences. This is nowhere more apparent than in the case of Oswald Avery. There were many great contributions to biology over the course of the 1900s, but arguably none more important than the Avery, et al. 1944 paper “Studies on the chemical nature of the substance inducing transformation of pneumococcal types.” Now, the last one hundred years have seen some amazing biological feats, and the Nobel foundation has caught a lot of them: double-helix nature of DNA, PCR, etc. However, without this one 1944 paper those discoveries wouldn’t have been possible, because we wouldn’t have been looking.

As with most things, this needs a little history to understand. Oswald Avery was born in Canada in 1877. His family moved to America while Avery was still young, and as a youth he displayed a great talent for oratory, music, and art. But he didn’t pursue any of these paths. Instead, he went into biology and medicine. Avery did not have a natural talent for this, at least so it seemed. His career was almost entirely unremarkable, that is until he was picked up by the Rockefeller Institute (and even there his first several publications were complete flops). This trend would continue until the eve of America’s involvement in WWI.

The Rockefeller Institute had essentially become the medical R&D arm of the government as Woodrow Wilson slowly forged America into a (really quite horrifying) war machine. The camps where soldiers lived during training (overcrowded in complete disregard for military hygiene rules) were really the most perfect breeding ground that disease could ask for. And it struck hard. Even before the infamous 1918 flu, the American training camps were hit by an epidemic of measles. Now, measles itself doesn’t kill you, but it does leave you open to secondary infections, most notably pneumococcus and it fell to Oswald Avery, now a private in the US Army (the entire institute had been inducted into the military practically overnight), to deal with the problem. And he did. Avery went after pneumococcus with a passion, studying it, cataloguing it, and working tirelessly to find some kind of vaccine.

It is difficult for me to believe that Avery did not first come across the transforming principle in his work, since we do know that he tried mixing live pneumococcus and heat-killed pneumococcus in his attempts to create a vaccine. But perhaps not. Or perhaps in the midst of war he failed to realise the significance of what he had done. But almost around ten years later, Frederick Griffith didn’t. Frederick Griffith was a British researcher trying to solve the same problem Avery had been: How to inoculate people against pneumoccocus. Once again he tried mixing live strains and dead strains of the bacteria. But something strange happened when he did that, and he took note. If he took a non-lethal strain and injected a rat with it, the rat was fine. If he took a heat-killed lethal strain and injected a rat with it, the rat was fine. However, if he took a non-lethal strain and a heat-killed lethal strain and injected a rat with both at the same time, the rat would die. Moreover live, lethal strain pneumoccocus could be isolated from the corpse. He happened upon the idea that the non-lethal strain could somehow be made into the lethal strain merely by being put in close contact. Something passed between them. This became known as “the transforming principle”.

No one really knew what to make of this. Although of course, the main theory was that it was due to genetic material being taken up by the living bacteria. Y’know, genetic material a.k.a. nuclear proteins. Because, after all, proteins are large and dynamic. That nucleic acid junk floating around in there was obviously just extraneous trash. Everyone believed this. Probably even Avery. When he returned to research on pneumococcus in the 1930s in an attempt to isolate the transforming principle, he most likely thought he was going in search of a protein. But bias has never been a friend to bleeding edge research, and fortunately Avery was able to look past that. He, Colin MacLeod, and Maclyn McCarty performed a series of experiment spanning more than a decade and published their findings in 1944: DNA was the transforming principle. Therefore, DNA was the most likely candidate for the genetic material.

This was it. This was the big one. We lost a century of scientific progress to phlogiston theory, how much time would molecular biology have remained stymied without Avery? Indeed, the understanding that DNA is the hereditary material laid the foundation for every advance that came afterwards. This is the lynchpin of modern biology, and every one of us who work in the field are personally indebted to him and his fellows. However, the initial reaction to Avery’s publication was very negative. Many scientists had a lot invested in this whole nuclear protein theory and some of Avery’s fellows at the Rockefeller Institute took the opportunity to slander him and his research at every turn. This included to the Nobel Foundation. Of course, once it became generally recognised (around 1950) that Avery was correct, the Nobel Foundation couldn’t just swallow its pride and admit error. So they staunchly continued denying Avery the award until his death in 1955 at which point he became ineligible.

Fortunately, by all accounts Avery really didn’t care about recognition (or really much besides his work), so we can hope he didn’t take offence. Of course, given the recent behaviour of some Nobel recipients perhaps we should be glad.

caudoviral