By David N. Leff

Science Editor

Two of the three scientists to be honored this year by Lasker Medical Research Awards work in the field of biotechnology.

Victor McKusick, founding father of medical genetics, will this week receive the Albert Lasker Award for "Special Achievement in Medical Science." He is University Professor of Medical Genetics at The Johns Hopkins University, in Baltimore.

Molecular biologist Mark Ptashne's Basic Medical Research Award recognizes his elucidation of the molecular basis of gene regulation during three decades at Harvard University.

The third recipient, research ophthalmologist Alfred Sommer, discovered that vitamin A can prevent blindness in millions of Third-World children. He is dean of the Johns Hopkins University School of Hygiene and Public Health.

The three 1997 Lasker laureates will receive their prizes at the annual awards luncheon on Friday in New York. Each award consists of a citation reciting its recipient's contribution to science, a $25,000 honorarium, and an inscribed statuette of the Winged Victory of Samothrace, symbolizing humankind's victory over disability, disease and death.

Since 1945, the Albert and Mary Lasker Foundation has honored the accomplishments of more than 300 basic and clinical science researchers. Of these, 56 went on to receive Nobel Prizes, giving the Lasker awards the reputation of being Nobel precursors.

Victor McKusick

McKusick is the second recipient of the annual Lasker award that honors career-long scientific achievement, rather than specific successes. Last year, the first such distinction went to molecular biologist Paul Zamecnik, who pioneered the theory and practice of antisense, and co-founded Hybridon Inc. (See BioWorld Today, Oct. 1, 1996, p. 1).

McKusick describes genetics as one of the few areas of medicine "to begin maturing [during the 1950s] in the basic research laboratory, rather than at the patient's bedside."

After other geneticists, in 1959, discovered the chromosomal defect causing Down's syndrome, McKusick observed, "Medical geneticists now had their specific organ — the genome — just as neurologists had the nervous system, and cardiologists the heart." Originally a cardiologist, McKusick created the division of medical genetics at Johns Hopkins in 1957, and hasn't looked back since.

A decade later, he compiled the first edition of Mendelian Inheritance in Man (MIM), which listed 1,500 then-known inherited disease phenotypes, presumably reflecting specific genes. That number has grown to nearly 9,000.

"Nowadays," McKusick told BioWorld Today, "I spend about 75 percent of my time keeping up with OMIM — the online version of MIM." He prefers to call this unabridged catalogue of human genes and genetic disorders a "knowledge base," rather than a database.

Electronic MIM, McKusick noted, "is distributed through the National Library of Medicine worldwide, and we get about 31,000 hits a day. Plus some drug companies, which download the whole thing, looking for targets for new drugs." The OMIM web site is at http://www3.ncbi.nlm.nih.gov/omim.

"As we speak," McKusick observed, "I'm in the throes of putting together the three-volume 12th edition of MIM in print. It's coming out this fall."

Currently, he said, MIM describes "about 650 genes, for which at least one disease-causing mutation has been identified. Some genes," he pointed out, "have multiple different diseases associated with them. For example, the beta-globin gene has sickle cell anemia, various forms of beta-thalassemia, methemoglobinemia, and so on. So, adding up all the different diseases on top of the 650 different genes, the different phenotypes identified come up to about 1,100."

McKusick continued, "Other than my attention to OMIM and MIM these days, my work is in seeing patients with genetic disorders and editing two journals — Medicine and Genomics.

Between 225 and 250 invited guests are expected at the awards luncheon. Winners have been advised that they may make three-to-five-minute responses upon receiving their prizes.

Asked what brief remarks he intends to make to the assemblage, McKusick replied: "I'm going to thank the Lasker people, and then tell Jim Watson [Lasker 1960; Nobel 1962], 'Jim, no matter what you say about me, I have the award now, and I'm not going to give it back.' "

In the 1970s, McKusick was a leading proponent of the Human Genome Project, and in 1988 he founded HUGO, the Human Genome Organization. He chaired the National Academy of Sciences Committee on DNA Technology in Forensic Science from 1990 to 1992. He also received 22 awards and honors between 1972 and 1997 — not counting this week's Lasker.

Mark Ptashne

Since 1958 at Harvard University, Mark Ptashne has been seeking — and finding —answers to the basic question: What regulates the genetic machinery that turns genes on and off?

In 1967, he isolated a regulatory protein in Lambda phage (a bacterial virus) called the "lambda repressor," and later showed how such regulatory proteins can recognize "information-specific" sites on DNA.

In 1980, Ptashne co-founded Genetics Institute Inc., of Cambridge, Mass.

Last month, Ptashne pulled up his 30-year stakes at Harvard and began moving his laboratory to the Memorial Sloan-Kettering Cancer Center, in New York, as professor of molecular biology.

Earlier this year, he told BioWorld Today, "We published a slightly polemical review in Nature, proposing a unifying view to explain the underlying chemistry of much of gene regulation, throughout all organisms."

Explaining his side of the polemic, Ptashne said: "We have argued, as to activating regions and their targets, that the activating region is simply a form of glue, which brings the holoenzyme to the DNA. This seemingly small point," he went on, "goes to the heart of how the whole system evolved, and how one can quickly evolve gene regulatory networks."

In other words, "contrary to what many people have believed, there is no specific site that activators must interact with to trigger gene activation. One alternative view." he elaborated, "goes something like this: 'The machinery is on the DNA, and now the activator comes along and triggers a conformational change, which then does such-and-such.' I think that view is wrong."

Ptashne plans to use his closing comments at the Lasker luncheon to say that "the success of the genome effort has made the role of basic research, using yeast and fruit flies and worms, much more important and relevant than it ever was before. To take one example, the lambda repressor turns out to have exact, almost duplicate, molecules, one of which, in fact, is known to be involved in a human disease — a form of dwarfism." *