I will be 65 this year, and my thoughts naturally keep turning to Oswald Avery, one of this century's great biochemists. On my table lies a book, "The Transforming Principle" (W.W. Norton and Co., 1985), an account of Avery's great discovery, told by his younger collaborator Maclyn McCarthy. It is a remarkable story.

      Biochemistry in the 1930 was downright primitive, compared to what it is today. Researchers of course knew about proteins and about the nearly endless variety with which they combined twenty basic building blocks to form the complex molecules of life. It was widely held that life and its origins involved proteins only, and yet, some pieces did not fit. In particular, there was DNA, a long stringy molecule folded into the nuclei of living cells, a repeating pattern a sugar, phosphoric acid and a seemingly random sequence of four non-protein building blocks. Before Avery's work no one knew the purpose of DNA. Some even thought it was just a structural brace, propping up part of the cell.

      Medicine was equally primitive, antibiotics were unknown and diseases such as pneumonia were often fatal. Researchers tried immunizations against pneumonia: it had worked well with other deadly diseases, but pneumonia germs turned out to have many varieties, and immunization against one did not always protect against others. A British scientist studying these varieties, Fred Griffith, made in 1927 a remarkable discovery: pneumonia germs could change from one type to another. If dead germs of type A were mixed with live ones of type B, some of the latter reverted to type A. A few years later it turned out that even clear fluid from dead germs of type A could produce the transformation. Whatever substance transmitted the genetic message defining type A germs, it must have been dissolved in the fluid.

      Around 1935 this puzzle attracted the attention of Oswald Avery, a senior researcher at the Rockefeller Institute in New York. A quiet, meticulous man, he was called "Fess" by his many friends, short for "professor." For his studies Avery not only used pneumonia germs, he needed them in great amounts--many, many pounds of them. So his lab grew the deadly stuff, separating it in a modified dairy cream separator. Yet his technique was so meticulous that there never was an accident.

      Patiently Avery and his collaborators searched for the substance which held the hereditary message. He chemically deactivated all proteins in his solution: no, that wasn't it, the solution still transformed germs. The sugar coating which protected the bacteria against the body's defenses, subject of other researches by Avery--that wasn't it, either. Gradually the search narrowed down to focus on DNA, that strange molecule of unknown purpose.

      As the book describes in great detail, it was a slow and complex search. It took Avery eight years or so to close in on his quarry, and by that time, in 1943, he had turned 65. He had planned to retire in Tennessee with his brother Roy, a professor of bacteriology, but this chase, late in life, was too exciting to give up. Instead he wrote to his brother, telling him how his plans had changed, that he was not yet ready to retire. The letter, now a historical classic, contained a clear and explicit description of Avery's work and his hopes. He concluded:

     

"So there's the story Roy--right or wrong, it has been good fun & a lot of work... ...don't shout it around until we're quite sure or at least as sure as present method permits. It's hazardous to go off half cocked, & embarrassing to have to retract later."

      It took another year or two before Avery had firm proof that DNA was indeed the stuff of heredity. Even then there existed doubters and scoffers, which is why he never received the Nobel prize. It was only after Watson and Crick found the double helix structure and after the genetic code was revealed, that Avery's achievement was fully appreciated. But it was too late, for he died in 1955.

      It is a rare privilege to approach one's 65th birthday feeling that the best is yet to come. Avery had that privilege, and he deserved it. Although I am a scientist too, I expect no such miracle. All I can hope is to hang on to my work, keep calculating, keep studying, keep it up, God willing, for perhaps a few years more. Yet the memory of Oswald Avery still seems to say to me that yes, even at 65, great things can still happen.