Peter Duesberg:
Berkeley Biologist Back in Spotlight 

LISA M KRIEGER/ San Jose Mercury News 27jan04

Peter Duesberg is once again a voice in the wilderness. But this time, he's not quite alone.

Best known for his contrarian views on AIDS, he now disputes the prevailing wisdom about cancer.

At a conference last weekend in Oakland, Duesberg and a group of 50 experts gathered to present data and debate the hypothesis that "aneuploidy," a term for duplicated or deformed chromosomes, is the cause of cancer.

Peter Duesberg

The theory held sway many years ago. But it was passed over by the newer view that an accumulation of specific gene mutations causes a cell to turn deadly. Scientists have even identified four to seven gene mutations that are believed to be necessary for a cell to become cancerous.

Duesberg, of the Department of Molecular and Cell Biology at the University of California-Berkeley, disagrees. He's thinking bigger.

The effects of changing chromosomes, which contain thousands of genes, are far more dramatic than the mutation of a few genes, he says.

"When nature really wants to change, it shifts chromosomes," he said.

Gray-haired, with a twinkle in his eye, the 66-year-old Duesberg is clearly buoyed by the newfound support of others.

For the first part of his career, Duesberg was in an elite group of scientists who competed for Nobel prizes and cornered most grants. Named a full professor at Berkeley in 1973, Duesberg received an Outstanding Investigator Grant from the National Cancer Institute in 1985 and was elected to the august National Academy of Sciences in 1986.

Then came AIDS. To the shock and disbelief of his colleagues, he asserted that AIDS is not caused by a virus—but is, instead, a disease stemming from drug abuse and immune-fatiguing factors. At a time when the medical community was urging safer sex to stop the epidemic, Duesberg was seen as undermining public health efforts.

Duesberg's career went into a tailspin. Funding dried up almost overnight. But he refused to budge from his stance.

"I have a clean record," he said, with characteristic bravado. "Before AIDS, none of my grant proposals were ever rejected; since then, nothing has been funded.

"It hardens you," he said of the AIDS controversy. "You're out on a limb."

Duesberg re-emerged on the scene in a paper published in 2000, when he reviewed many of the inconsistencies dogging the mutation theory of cancer.

This resuscitated interest in his alternative theory, aneuploidy. This theory holds that cancer-causing agents—such as radiation or toxins like smoke, for instance—disrupt the process of normal cell division, creating errors. Pieces of chromosomes may be missing, or copied more than once. With cell replication, these errors lead to more errors.

His paper caught the eye of many who are frustrated with the slow progress against cancer. Venture capitalist Robert Leppo, former director of the Web marketing company Value Click, offered to bankroll Duesberg's research, as well as the conference.

Among those attending were Dr. Gert Auer, professor in the Institute of Oncology-Pathology, Karolinska Institute in Stockholm, Sweden; Dr. Thomas Ried, chief of cancer genomics, National Cancer Institute in Bethesda, Md.; and Wilma Lingle, assistant professor of pathology, Tumor Biology Program, Mayo Clinic in Minneapolis, Minn., among others.

Yet many mainstream scientists view Duesberg as a wolf in the henhouse. Critics include prestigious William Hahn of Harvard Medical School and Robert Weinberg of the Whitehead Institute for Biomedical Research in Cambridge, who have shown that, contrary to Duesberg's claims, a variety of human cells can be made cancerous without aneuploidy.

No one disputes that aneuploidy happens.

But most experts—including some at the conference—believe that aneuploidy is one step or the first step, but not the only step, in cancer. Some dismiss it as only an effect, not a cause, of cancer.

"It's wrong. It's too simplistic," said Martyn T. Smith of Molecular Epidemiology and Toxicology Laboratory at UC-Berkeley. "Things have moved on.

"That is not to say that aneuploidy is not important to cancer. It just means that it is not the only potential mechanism," Smith said. "It could be one of many ways the genome is destabilized. There are many changes. Aneuploidy could be one of them."

David Eastmond, professor of Environmental Toxicology at the University of California-Riverside, agreed. "There are many genetic changes in cancer. Aneuploidy is an important one, but not the only one.

"There are other pathways to carcinogenesis, as well," Eastmond said. "In some cancers, it is not obvious that aneuploidy is playing a role. In others, it is more directly involved."

Duesberg is energized by the debate. When disputed, he rises to the challenge, sometimes shouting.

"It's stimulating. It gets the adrenaline going," he said. "You live only once. I didn't want to see this theory abandoned or overlooked."

No other theory adequately explains cancer, he said. "It's the one."

source: http://www.mercurynews.com/mld/mercurynews/living/health/7801855.htm 27jan04