Happy birthday, Max Delbrück!

by Matthew Cobb

As Jerry pointed out earlier, the scientist Max Delbrück was born 110 years ago today. Because many readers will never have heard of him, Jerry asked me to sketch his life. Here you are:

Max Delbrück (1906-1981) was a key figure in the history of post-war genetics, pioneering the molecular investigation of viruses, and winning the Nobel Prize in Physiology or Medicine in 1969 “for discoveries concerning the replication mechanism and the genetic structure of viruses”  Born in Germany, Delbrück trained as a physicist and worked in Copenhagen with Niels Bohr on quantum mechanics before turning to biology in the 1930s. In 1935, together with the Russian geneticist Nikolai Timoféeff-Ressovsky and the radiation physicist Karl G. Zimmer, Delbrück published a paper in German entitled “On the Nature of Gene Mutation and Gene Structure,” known subsequently as the “Three-Man Paper.”

This important piece of research was recently translated into English, together with an excellent introduction. In 1942, this paper, which attempted to explain the size of genes – which the three men assumed to be proteins – and their mode of mutation, caught the eye of the quantum physicist Erwin Schrödinger, who was in Dublin, preparing for his inaugural lecture under the title ‘What is Life?’ in 1944 this lecture (in fact, there was so much material it turned into three lectures) was published in a small book, and it has never gone out of print since.

Schrödinger’s account of how physics could be used to investigate biology, including his emphasis on Delbrück’s model of mutation, entranced a generation of scientists, many of them physicists. Watson, Crick and Wilkins, who won the Nobel Prize for the double helix structure of DNA in 1961, were all inspired by Schrödinger’s book, and by Delbrück’s approach.

In the 1940s (he had by now fled Nazi Germany for the USA), Delbrück, together with his friends and colleagues Al Hershey and Salvador Luria, began working on viruses that infected bacteria – these were known as ‘bacteriophages’ and the researchers who studied them were later called ‘the phage group’. The idea was that by studying viruses and their mode of replication, you could learn something fundamental about how life works, as viruses were seen as been like a kind of fundamental living particle.

Delbrück (left) and Luria at Cold Spring Harbor Laboratory, during the ‘phage course’ the late 40s-early 50s.

Among the young researchers the phage group attracted was Jim Watson, who famously switched from ornithology to molecular genetics. Much that is good – and some that is bad – of molecular biology lab traditions that exist around the world flow from the way that Delbrück worked. To spread the techniques that were employed in his niche area, he set up a training course at Cold Spring Harbor Laboratory (the ‘phage course’), where budding molecular geneticists could learn key techniques.

This open, sharing attitude to science was important for ensuring that methods and findings were quickly transmitted. The social side of lab work was important, too – he and his lab members would go on hiking trips on the weekend. Meanwhile, when it came to data there were no holds barred and precise, even pedantic and aggressive questioning of speakers and people presenting their data were the norm.

Delbrück was famous for denouncing findings, generally mistakenly. For example, when Seymour Benzer presented data showing that he had created a Drosophila mutation that altered the fly’s body clock, Delbrück walked out of the lecture, saying “I don’t believe a word of it!”. Benzer was right, and Delbrück was wrong.

Delbrück’s reputation for backing the wrong side in any scientific argument led to a joke, according to which a young researcher came out of Delbrück’s office looking pale; “What’s up?” a friend enquired. “Didn’t he like your results?’ “No,” said the researcher, aghast: “He said he thought they were right.” Ho ho.

Probably the best and most perplexing example of this attitude took place in 1943, when Delbrück, who was then at Vanderbilt University in Nashville, was shown a letter from Oswald Avery, a bacteriologist who worked at the Rockefeller Institute in New York. Avery had written to his brother, who worked at Vanderbilt, describing the amazing results he had found which suggested that, in pneumonia bacteria, genes were made of DNA.

This result, which was not published for another eight months, would eventually transform the whole of biology and medicine, and Delbrück was one of the first people to hear about it. What did he do? Nothing. He did not immediately try and see if his bacteriophage viruses used DNA, he simply ignored the discovery. “You simply did not know what to do with it,” he later said. Delbrück was not alone – other researchers similarly did not accept, or understand, Avery’s finding.

But Delbrück was a very smart man who was interested in what genes are made of. It is bewildering why he did not ‘get it’, while many others, such as the young student Erwin Chargaff, or the French bacteriologist André Boivin both immediately and enthusiastically adopted the new DNA-centred view, helping to shape post-war biology as they did so.

Delbrück was an inspiration to many researchers, and his influence, in particular his skepticism and his attention to detail, is a tremendous legacy. He even played an important role in showing that how evolution by natural selection works. In a 1943 experiment that many researchers claim to be their favourite ever (yes, we all have favourite experiments!) Delbrück and Luria showed that mutations occur randomly, using bacterial resistance to bacteriophage. [JAC: My favorite experiment is the Meselson and Stahl experiment showing that the replication of DNA is “semiconservative.”]

Finally, history could have turned out very differently. A couple of years back, I learned that in 1946 Delbrück accepted a job at the University of Manchester, where I work, where there were researchers studying viruses and, famously, Alan Turing was turning to work on biological questions, in particular pattern formation. Delbrück visited Manchester, signed on the dotted line, and then for some reason that I cannot explain, chose to go back on his word and abandon bomb-damaged, smoke-blackened post-war Manchester for the sunny heights of the California Institute of Technology.