Maclyn McCarty, Pioneer in DNA Research -- Rest in Peace

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Subject: Maclyn McCarty, Pioneer in DNA Research

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Dies at 93

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Date Posted: January 07, 2005 1:36:16 EDT

Dr. Maclyn McCarty, the last surviving member of a Manhattan scientific team that overturned medical dogma in the 1940's and became the first to demonstrate that genes were made of DNA, died on Sunday. He was 93 and lived in New York.

His death was announced by Rockefeller University, where he worked for more than 60 years.

Dr. McCarty was also a renowned leader in research on the biology and immunochemistry of the streptococcus bacterium and its role in producing rheumatic fever.

The work that Dr. McCarty did in the 1940's, with Dr. Oswald T. Avery and Dr. Colin MacLeod, strongly hinted that DNA was the stuff of life and paved the way for the field of molecular biology and genetic engineering. Their evidence came from experiments on the pneumococcus, at what was then known as the Rockefeller Institute for Medical Research.

Until the team's findings, published in 1944 in the Journal of Experimental Medicine, scientists believed that genes must be made of protein, Dr. McCarty said. Although DNA had been identified in the mid-19th century, little was known about its biological activity, and most scientists believed that DNA lacked the necessary complexity to carry hereditary information.

"There is no question that the 1944 paper was the turning point in the concept that the chemistry of genes was DNA," said Dr. Joshua Lederberg, a Nobel Prize-winning scientist and a former president of Rockefeller University. "It was the pivotal discovery of 20th-century biology."

The findings fell mostly on deaf ears for about a decade before playing a pivotal role in the determination in 1953 by Dr. James Watson and Dr. Francis H. C. Crick that the structure of DNA was a double helix, a discovery for which the two shared a Nobel Prize.

On the 50th anniversary of the Watson-Crick discovery, Dr. McCarty wrote in the scientific journal Nature that while he was "pleased to see such illuminating results," he was "not so pleased that they failed to cite our work as one reason for pursuing the structure of DNA."

Although Dr. McCarty and his teammates were nominated for a Nobel Prize, no member ever won one.

Dr. Alfred D. Hershey, a former director of the Carnegie Institute, once said that the trio's work attracted little attention in part because "they were just too modest; they refused to advertise."

Nobel Prize nominations are complicated, Dr. Lederberg said, "but everybody including the Nobel Committee will acknowledge that this was their most significant failure." He added, "There must be 20 to 25 prizes that have been awarded for work that depends on the team's seminal paper."

In 1994, Dr. McCarty received a Special Achievement in Medical Science award from the Lasker Foundation, which many consider the American equivalent of a Nobel Prize.

Maclyn McCarty was born in South Bend, Ind., on June 9, 1911. He graduated in 1933 from Stanford, where he majored in biochemistry. He went on to earn his medical degree at Johns Hopkins University in 1937. He then trained in pediatrics for three years at Johns Hopkins with a special interest in infectious diseases.

Dr. McCarty spent a year doing research on sulfonamide drugs at New York University before he moved to Rockefeller. There, he unexpectedly joined Dr. Avery when Dr. MacLeod left to become chairman of microbiology at New York University. From 1942 to 1946, Dr. McCarty was a lieutenant commander in the Navy Medical Corps, working with the Naval Medical Research Unit based at the Rockefeller Institute Hospital.

Scientists knew that the S (smooth) form of pneumococci had a thick outer wall that protected them from a person's immune defenses, while the R (rough) form lacked such a wall and could be virulent. The team showed that an inherited factor in the bacteria could be transferred from the nonvirulent to the virulent form.

Dr. McCarty applied his biochemical skills to use enzymes to purify the transforming factor and to degrade different classes of molecules to identify the factor as DNA. He went on to purify and crystallize for the first time an enzyme that degrades DNA, to verify that the genetic material was DNA and to lay to rest the doubts that it was of protein origin.

In a 1998 interview, Dr. McCarty said that the faculty lunchroom at Rockefeller provided a rich forum for discussions with scientists from a broad array of disciplines.

In 1946, Dr. McCarty became head of the Laboratory of Bacteriology and Immunology at Rockefeller, and concentrated on rheumatic fever.

Scientists in his laboratory studied the streptococcal-rheumatic fever link from different perspectives. Through chemical analysis, his team identified the major components of the streptococcal cell-wall structure. Rebecca Lansfield, a member of his team, developed a standard classification system for streptococci now known by her name.

Dr. McCarty was a vice president of the university and physician in chief at the Rockefeller University Hospital. He was also board chairman of the Public Health Research Institute of the City of New York.

In his later years, Dr. McCarty benefited from his own research when he developed anemia: genetic engineering techniques were used in making the drug he took to help produce more red cells.

Dr. McCarty's first marriage, to the former Anita Alleyen Davies, ended in divorce. He is survived by his wife, the former Marjorie Fried; two sons, Richard E., of Baltimore, and Colin Avery, of Clifton Park, N.Y.; a daughter, Dale Dinunzio of Bradenton, Fla.; eight grandchildren and five great-grandchildren.

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