For more than 30 years, Dr. Bruce Stillman, president of Cold Spring Harbor Laboratory and director of its cancer research center, has probed the inner sanctum of cells - the nucleus - and has produced groundbreaking discoveries, changing what the world knows about DNA.
Now, he and a colleague, Dr. Thomas Kelly, who heads the Memorial Sloan-Kettering Institute, the cancer center's research arm, have jointly won the prestigious Louisa Gross Horwitz Prize administered by Columbia University for outstanding basic research in biology. Forty-two of the 82 awardees who've received the award since its inception in 1967 have gone on to win the Nobel Prize.
The Horwitz award recognizes discoveries that span scientists' careers. Although Stillman is reluctant to forecast whether he's headed for the rarefied company of Nobelists, he's certain of this: He will never stop studying DNA.
A native of Australia who never lost his accent, Stillman has worked continuously at Cold Spring Harbor Laboratory since arriving in 1979 as a postdoctoral investigator. During an early point in his career, his laboratory adjoined that of famed Cold Spring Harbor geneticist Barbara McClintock who won the Nobel Prize for her work that focused on genes in corn.
Stillman, however, is committed to human DNA and the genetics of cancer. To understand the latter has meant decoding many basic - but complex - mechanisms governing the master molecule of life.
While most people think of DNA's configuration as the iconic double helix, in the nucleus it is actually a fiercely wound wad, balled tighter than the Great Gordian Knot.
Stillman and colleagues are credited with advancing scientific knowledge by revealing which mechanisms must be in play for the wad to unwind and for replication to take place.
"In every cell in our body there is about 6-feet of DNA that is all packaged up in a tiny, tiny compartment in the cell called the nucleus, and every time the cell duplicates, the DNA has to become 12 feet," Stillman said.
Because each individual cell divides to produce two new cells, the 12 feet of DNA must be clipped by molecular scissors to accommodate the two new "daughter" cells, each of which must contain six feet of DNA.
Working collaboratively with Kelly and teams of biologists at both institutions, the two researchers over the last few decades deciphered some of nature's best-kept secrets, and particularly how simple mistakes - what Stillman calls spelling errors - underlie the genetic derangements that lead to cancer. Kelly was unavailable for comment.
Stillman alone, however, is credited with discovering the so-called origin replication complex, or ORC, a constellation of proteins that serve as the molecular switch that begins "unzipping" the double helix, preparing it for the copying process.
He pinpointed each highly choreographed step in that biological dance, which yields two sets of identical chromosomes that pull apart to become two new cells during cell division. With 100 trillion cells in the adult human body, replication is carried out countless times a day in billions of people worldwide, usually flawlessly.
"We figured out that there is a very complex copying machine in the cell and we figured out how it works," said Stillman, adding that the copying process is highly regulated "to copy only once because if you get extra copies, that can lead to cancer. Cancer is a process where the copying process has gone wrong and has errors," Stillman said.
Dr. Wayne Hendrickson, chairman of the Horwitz Prize said in a statement that Stillman and Kelly have boosted basic scientific knowledge tremendously by uncloaking the main constituents in how DNA copies itself.
"These two investigators, more than any others, are responsible for discovering the key molecular players and the principles that govern the process of genetic replication," Hendrickson said.