For seminal and historic investigation which revealed that DNA is the chemical substance of heredity and for ushering in a new era of contemporary genetics.
The opening of the contemporary era of genetics—triggered by the historic discovery that genes are made of DNA—was achieved 50 years ago this year by Maclyn McCarty and his Rockefeller Hospital colleagues, Oswald Avery and Colin MacLeod. This pivotal discovery of the 20th century led the way for stunning revelations in DNA technology, most dramatically in 1953 with Watson and Crick’s defining of DNA’s double helix configuration. The reverberations continue today, dominating large sectors of biomedical science and biotechnology, and have established the centrality of genetics in biological thought.
In the 1940s, DNA was an unlikely candidate for biological specificity since a homogenous sample of DNA appropriate for chemical analysis was not available. But Avery had done much earlier work with pneumococcal pneumonia and extensive studies with the pneumococcal cell itself. The Avery Lab was the only place where attempts were being made to identify the substance involved in cellular transformation. Then, in early 1940, with MacLeod and McCarty, Avery began the slow, painstaking work that culminated in the historic chemical characterization that the transforming substance—the manner in which the pneumococcus controlled the formation of its capsule—was a highly polymerized viscous form of deoxyribonucleic acid.
Their work was meticulous and exacting. The 1944 paper, in fact, has been called a model of factual statement and analysis. In the next ten years alone, the paper was cited almost 300 times in other work and very frequently cited by indirection.
Confirmation of their findings came quickly and other researchers around the world began extending knowledge of DNA. McCarty himself went on to purify a DNase from beef pancreas and showed that the enzyme efficiently inactivated the transforming principle, something that depolymerases for protein, RNA, and polysaccharide had previously failed to do.
But perhaps most important, their work opened the door to a new age of understanding genetics and an era of inquiry into the most basic issues of fundamental biological science. As Sir Peter Medawar said, it was “the most interesting and portentous biological experiment of the 20th century.”
To Maclyn McCarty, for his seminal and historic investigation which revealed that DNA is the chemical substance of heredity, and for ushering in a new era of contemporary genetics, this 1994 Albert Lasker Special Achievement Award is given.
An Interview with Maclyn McCarty
Dr. Maclyn McCarty’s September 3, 1998, conversation with Bradie Metheny, publisher of Washington Fax, provides a personal glimpse into the life of Dr. Oswald Avery.
Metheny: I would like you to give me a bit of a personal glimpse of Dr. Avery, as an individual, as a man, and some of his philosophy. And I do have one question on the science. He was into pneumococcus. How did he get from that to the transforming principles of DNA?
McCarty: That all came from the pneumococcus. The whole story is a pneumococcal story.
Metheny: I see. Was that easily recognized by everybody else?
McCarty: Well, no. Actually, it represented a phenomenon called “transformation of pneumococcal types” that was discovered in England by a man named Griffith. At the time it came out—it was reported back in 1928—Avery had been working with pneumococcus for a number of years, and it was a phenomenon that surprised him. As a matter of fact, they might have been skeptical if they didn’t have a high respect for Dr. Griffith. But they did repeat it in their laboratory. It was also confirmed in a laboratory in Germany in the Salk Institute by another man who was a pneumococcal expert.
So it was there. The explanation for it and what was happening was not known, and as time went on, Avery became focused on the fact that it probably would be important to find out the nature of this substance that was responsible for transformation. You could extract the substance from one type of pneumococcus, and with the material that you extracted, you could proceed in culture and get a different type of pneumococcus to make the material that was made by the first type.
As one thought about it after working with it for a long time, it was clear that it had the features of the transfer of genetic information. Avery’s idea was that we ought to stick with it and try to find out what it was. Nobody else pursued that course.
Metheny: And that was DNA.
McCarty: And that was DNA.
Metheny: Wasn’t there a bit of debate whether it was protein that was the basis for life?