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Tuesday, May 1, 2012

Cancer Wars: An Outcast Researcher’s New Theory

PACIFIC STANDARD

Cancer Wars: An Outcast Researcher’s New Theory

The scientific community disowned Professor Peter Duesberg for denying that HIV causes AIDS. But is there something to his new theory on cancer?


Peter Duesberg, a professor at the University of California, Berkeley. (Timothy Archibald)
 

Compact and white-haired at 75, Peter Duesberg has wide-set blue eyes magnified by corrective lenses as thick as his German accent. He is the picture of a courtly Old World scientist. But Duesberg is given to through-the-looking-glass scientific theories, the most recent of which, about the origins of cancer, could turn an accepted truth of molecular biology on its head. Viruses like hepatitis C don’t cause cancer, he says, and neither do collections of mutated genes — as nearly every other scientist believes. Instead, he argues, cancer arises when the number and appearance of a cell’s chromosomes become disrupted, leading to a tumor that has, in effect, evolved into a parasitic new species.

Some scientists think he could have a point. “There is something to what Peter Duesberg says,” says Mark David Vincent, a Canadian researcher and oncologist whose own unconventional theories about cancer overlap with Duesberg’s. But most others are skeptical. One reason may be that Duesberg is a pariah for his​ tenaciously held theory that HIV does not cause AIDS.
Duesberg works in a shabby laboratory on the campus of the University of California, Berkeley. He runs his experiments virtually alone. He has no graduate students and little staff support, and virtually no research budget, apart from some limited private funding. Duesberg acknowledges that if he weren’t a tenured full professor, he probably would have been gone long ago.
Duesberg once was highly respected by his peers. After arriving at Berkeley in 1964 with a doctorate in chemistry from the University of Frankfurt, he, in short order, extracted the RNA of the Rous sarcoma virus, shown to cause tumors in chickens, and in 1970 co-discovered a viral gene that seemed to promote cancer. He also helped plot the retroviral genome and won election to the National Academy of Sciences. “For a while I was the blue-eyed boy,” he says. “Now I’m the traitor from within.”

Duesberg’s career took a turn in March 1987, when he published a paper in Cancer Research that made two sensational claims: One was that retroviruses did not activate cancer-promoting genes; the other was that the newly identified HIV retrovirus did not cause AIDS. It did cause minor mononucleosis-like illness, he conceded, but not the lethal AIDS symptoms. As he explains it, “These questions were lingering in my mind. Why do we say these retroviruses are so bad when they’re found everywhere and hardly anyone ever gets sick?”
He would subsequently argue that gay men were dying as a result of their allegedly prodigious drug use rather than AIDS. Later, as the HIV genome was sequenced and antiretroviral drugs were introduced, he contended that the drugs themselves were causing the symptoms attributed to AIDS. Hemophiliacs who became infected through blood transfusions were already sick, he argued, and in sub-Saharan Africa, where AIDS was spreading among heterosexuals, malnutrition and parasites were the real culprits.

These ideas were discarded as further research supported the HIV hypothesis. But Duesberg seemed immune to the evidence, raising ever-flimsier objections to each new finding. He argues, for example, that Africa’s population wouldn’t have continued growing over the past few decades if AIDS really is a lethal communicable disease. Other scientists stopped taking him seriously. His government research funding dried up, and, for many years, most peer-reviewed scientific journals refused to publish his papers. So he took his case to the public, publishing a book and developing a small but devoted following, particularly among conspiracy theorists.

One of those followers was South Africa’s President Thabo Mbeki, who, in 2000, invited Duesberg, among other HIV skeptics, to serve as a consultant in shaping his government’s AIDS policies. Over the next few years, government officials cited Duesberg when refusing to promote the use of antiretroviral drugs. A 2008 study by two Harvard School of Public Health researchers, Pride Chigwedere and Max Essex, estimated that more than 330,000 South Africans had lost their lives to HIV/AIDS between 2000 and 2005 because of these policies, and it mentioned Duesberg by name. “The science behind Mbeki was Duesberg and other denialists,” Chigwedere and Essex wrote in a 2010 follow-up article.
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Duesberg remains unrepentant. And he’s been equally stubborn about his radical theories on the origins of cancer.

His research in the 1970s had focused on tumor viruses because they were thought to alter human genes, thereby causing cancer. But as other scientists found evidence that humans carried genes that could mutate and drive cancer, Duesberg grew skeptical. For one thing, an ever-growing number of mutations seemed to be needed — dozens, in some cases — which he found implausible. Meanwhile, in Duesberg’s view, the mutation theory was further undermined by studies showing that many known carcinogens did not cause gene mutations in the first place.

Billions had been spent on the war on cancer, yet scientists had made little progress toward a cure. Could the research establishment be on the wrong track? “Nobody asks these questions,” Duesberg says. “People are so well trained not to ask negative questions.”

His focus shifted to the abnormal number of chromosomes that virtually every cancer tumor has — an observation first made by German scientist Theodor Boveri in the early 20th century. Most human cells have 23 pairs of matched chromosomes, half inherited from each parent, for a total of 46. This pattern is preserved each time the trillions of cells in our body divide and replicate. But in cancer cells something goes awry: there might be three or four chromosomes where there should be a single pair, or the chromosomes might be abnormally foreshortened. Such cells are described as “aneuploid.”

In a paper he published last summer in the journal Cell Cycle, Duesberg theorized that carcinogens might cause chromosomes to divide abnormally during cell division, creating extra copies of thousands of genes and disrupting the cellular machinery — an idea with parallels to a theory floated by Julian Huxley in 1956. These aneuploid cells usually die, but every so often the new genetic arrangement — called the karyotype — might enhance a cell’s ability to survive and clone itself. As these clones multiply, a tumor can emerge with a new, stable karyotype. The way Duesberg sees it, that tumor would essentially be a unique species, a parasite that feeds off its host.

Duesberg’s model resembles ideas advanced by some other researchers, including Henry H.Q. Heng, a molecular geneticist at Wayne State University, as well as Mark David Vincent, who treats lung cancer patients at the London Health Sciences Centre in Ontario, Canada. Vincent, who has referenced Duesberg’s theory in his own papers, believes that cancerous cells exploit an ancient survival mechanism, reverting to the form of protozoa-like organisms from before the time when single cells began cooperating to create multicellular organisms like us. “It became clear to me that the process of carcinogenesis involved a form of life emerging that was different from the host,” Vincent says. “We sort of converged on the same thing but from a somewhat different perspective.” Vincent sides with mainstream researchers in believing that genetic mutations are one of the things that initially turn normal cells cancerous. But he agrees with Duesberg that aneuploidy, which can entail a rapid reshuffling of genes, likely helps drive the growth and spread of tumors.
Vincent, who says people have warned him that Duesberg is “radioactive,” disagrees with the Berkeley scientist’s HIV/AIDS claims. But, he adds, those ideas don’t make Duesberg’s cancer theories wrong. “Anybody who thinks courageously outside the box and in a different way is an extraordinarily important resource,” he says. Besides, whatever the error of Duesberg’s views, “we should not censor people intellectually.”
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Duesberg sometimes seems to relish his status as an outsider, portraying himself as a victim of groupthink who has been persecuted for daring to question the status quo. Other times, he sounds almost wistful. “I was immensely popular,” he says of the days when he found the first cancer-causing oncogene in the Rous sarcoma virus. “I would have been served so much better if I had stayed with oncogenes as the cause of cancer.”

Now, he says, even his Berkeley colleagues largely shun him. As recently as 2010, he says, the university investigated complaints that he had published a paper containing false claims—a response of sorts to the Chigwedere and Essex findings — in a non-peer-reviewed publication. A university spokesman says no action was taken because tenured faculty members are guaranteed academic freedom to advance their theories — with the peer-review process serving to safeguard accuracy.

He hasn’t trained any graduate students in 15 years and only recently was permitted to begin teaching an undergraduate course called “The Cancer Karyotype: What It Is and What It Does.” He runs a few experiments in his lab, almost single-handedly (sometimes with help from an undergraduate student or two), but it’s evident the fall has been painful.

“I think I was even close to a Nobel,” Duesberg says. “If I had just shut up, I would have been much better off.”

Without prompting, he ticks off the names of scientists who’ve won Nobel Prizes for contributing to the standard mutation model of cancer genetics. “All the sheep think the same thing: mutations cause cancer, and HIV causes AIDS,” he says. But he maintains that in his acid skepticism he’s upholding the purity of the scientific method. “Science is absolute,” he says. “You question things that you were taught or were told by your priest, your führer, or your teacher — or anyone.” Whenever a scientist worries about what others will think or the moral implications of his work, “it’s not good science anymore,” he asserts. “It should be amoral — without morals.”

This article appeared in the May-June issue of Pacific Standard under the title “The Heretic.”

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