YOU ARE HERE: LAT HomeCollections


Theodore Puck, 89; Modest Biologist Laid Groundwork for Unlocking Mysteries of DNA

November 11, 2005|Thomas H. Maugh II | Times Staff Writer

Theodore Puck, the biologist who was a key player in making it possible to work with human cells in the laboratory and whose work laid the foundation for the human genome project, died Sunday in Denver. Puck, 89, died of complications from a broken hip suffered in a fall.

His studies on human cells grown in the laboratory showed for the first time how little radiation was necessary to kill cells; provided insights into how chemicals in the environment affect DNA; and confirmed the precise number of chromosomes in the human genetic blueprint, which was the subject of controversy when he began his work.

Puck won the Albert Lasker Award for Basic Medical Research in 1958 as well as other prestigious awards during his 65-year career, but he never received the Nobel Prize, which many researchers considered a great affront.

Puck "was a giant in the field in his time," said Dr. Janet Rowley, a geneticist at the University of Chicago, "but he was quiet and unassuming, which is why he was underappreciated. As with any profession, notice tends to be given to those who talk a lot and talk loudly about their work, but that was not his style."

When Puck began his research in the 1940s, human and other mammalian cells were nearly impossible to grow in the laboratory. That meant biochemical and genetic studies had to be carried out on living humans, which precluded many types of promising studies.

Puck reasoned that the cells were not getting proper nutrients. To overcome the problem, he lined the bottom of a laboratory dish with a layer of cells, such as mammalian kidney cells, and irradiated them so that they could not replicate. The animal cells, called "feeder" cells, produced growth factors and other nutrients required by the human cells.

He found that human cells would grow nicely on the feeder cells. But the problem in research was that it sometimes was difficult to determine whether an observed reaction was due to the human cells or the feeder cells.

Puck and other researchers, including Richard Ham, spent months devising an appropriate cocktail of 30 to 40 individual nutrients, sugars and salts necessary for growth. They also showed that precise temperature control was crucial and that the cells had to be grown in an atmosphere containing 100% humidity and 5% carbon dioxide, developing special incubators to keep the cells alive.

His techniques are now used to grow cells in laboratories throughout the world, but he never made a penny from his findings. "I was really stupid," he said later. "I never patented anything."

Once he was able to grow cells, it was obvious that he had a new tool for studying human genetics; previously, researchers had been limited primarily to genes in reproductive cells. He coined the term "somatic cell genetics" to cover the study of genes in cells other than sperm and eggs.

One of his first projects was to study the effects of radiation on the cells. By exposing the growing cells to precise amounts of radiation, he was able to determine how much was necessary to kill them or to induce mutations.

He found that the lethal dose of X-rays was about 1% of what researchers had previously believed it to be. Those studies paved the way for the use of radiation to treat cancer by showing oncologists how much radiation they could safely use.

They also exposed the cells to soil contaminants, food additives, factory wastes and other materials, identifying breaks and gaps in the chromosomes that signaled mutations.

By the mid-1950s, there was still controversy about the number of chromosomes that make up the human genetic blueprint. Conventional wisdom at the time was that there were 48 -- 24 pairs -- although some researchers thought that there were 47 and others argued for the now-accepted number of 46.

In January 1956, a young Chinese researcher named Joe Hin Tjio published a report in an obscure Scandinavian journal that argued that the correct number was 46.

The paper was largely ignored because Tjio did not have a doctorate. But Puck was intrigued and invited Tjio to come to Denver to earn his doctoral degree and work with him.

The two photographed 2,500 samples of cells and found 46 chromosomes in 2,498 of them, thereby firmly establishing the correct number.

But even with the number determined, researchers often gave different names to individual chromosomes, making communication among labs difficult and error-prone. In 1959, Puck called all the researchers working in the field to Denver, where they reached an agreement to provide a uniform numbering system. The essentials of that agreement, called the Denver System, remain in use today.

Theodore T. Puck was born in Chicago on Sept. 24, 1916. He obtained his undergraduate and graduate degrees in physical chemistry from the University of Chicago. After a series of short-term appointments, he joined the University of Colorado Medical School in 1948 and remained on the faculty until his death.

In 1962, he founded the Eleanor Roosevelt Institute for Cancer Research in Denver and led it until his formal retirement in 1995.

After his departure, the institute suffered financial problems and was absorbed by the University of Denver in 2003. Puck continued his work, however, and was in his laboratory in the week before his death.

Puck is survived by his wife, Mary; daughters Stirling Puck of Santa Fe, N.M., Laurel Northup of Bethesda, Md., and Jennifer Puck of Bethesda; and seven grandchildren.

Los Angeles Times Articles