The inadvertent healer

January 22, 1999

Biologist and author Robert Weinberg tells Tim Cornwell how years spent in cancer research are finally about to bear fruit.

Robert Weinberg avoids red meat, particularly when it is burnt. While he is not an epidemiologist - someone who studies the incidence of cancer in the field - as one of the United States's foremost cancer researchers he knows a health risk when he sees one. The blackened meat of the backyard barbecue, that savoury expression of the American (and British) good life, is "probably as bad as smoking cigarettes".

"Stay away from it altogether," he says, noting in the same breath: "I'm not on any crusade about this." He describes meat roasted on the grill: "Real bad. If you look at the blackened part of meats, on the outside of meats, its absolutely chock full of potential carcinogens. Just wonderful. No, not wonderful," he adds quickly, "but you understand what I mean. I study cancer.

"I'm a PhD, not an MD. I'm not a real doctor," Weinberg says. But lately he has begun to feel like a proper healer: this winter, a breast cancer drug developed at the biotechnology company Genentech Inc - but rooted in research Weinberg carried out 17 years ago with a team at Massachusetts Institute of Technology - appears on the US market.

Herceptin is reported to slow and even shrink breast cancer tumours, offering terminal breast cancer victims precious extra months of life. It is among the first of a new and promising generation of genetically based cancer treatments that draw on two decades of research.

"I don't know how many cancers it is going to cure, but it may prolong life and decrease suffering," Weinberg says. "It is the first concrete benefit that my work has yielded in terms of actually helping people. In the next decade there are going to be some dramatic new cancer drugs."

This week sees the British publication of Weinberg's latest book, One Renegade Cell. Cancer stalks the pages like an off-stage killer. The cancerous cell of the title is the "elusive quarry", the "enemy within", a mass murder suspect whose hiding places - inside our own bodies - are painstakingly revealed. A book that begins with a "brief primer" on the DNA double-helix in chapter one - just six succinct pages - remains a page-turner in part because death lurks on the other side of the door. After all, two in five people in the US will develop cancer and one in five will eventually die from it.

But the book is also a compelling piece of scientific writing, one that impels the reader to understand rather than to skirt. Weinberg's own research, though described in the New York Times as "an achievement of incalculable magnitude", appears sparingly. He wrote One Renegade Cell as part of publisher Weidenfeld and Nicolson's "Science Masters" series after penning Racing to the Beginning of the Road, a "chatty history" of cancer research, which is also published in the United Kingdom this month.

One Renegade Cell was intended to explain the consequences of that research, laying out what we have learned of cancer's origins. Faced with this formidable task, it bears the hallmark of a top researcher forced to talk intelligibly to the non-specialist. Weinberg says he set out to deliver "major take-home lessons" without being didactic or too technical, just as he does in his introductory biology class at MIT.

"I don't think of myself as a writer. I think of myself as a teacher," he says. "It's my feeling that biology is actually conceptually very accessible. It's not something like theoretical nuclear physics, where one needs decades of study to understand the subtleties. Biology is very intuitive."

Cancer tumours may appear like alien invaders that wreak havoc on the body, but "appearances deceive", Weinberg writes. "The truth is much more subtle and endlessly interesting." Cancers are created from normal human cells run amok and may take decades to grow to a detectable size, with tumours comprising a billion or more cells before we are aware of them.

In our bodies, there are "highly complex societies of rather autonomous cells" gathered in a "single, highly functional cooperative" from which one sociopathic cell goes its own way. "This founder, this renegade cell, decides to go off on its own, to begin its own growth programme within one of the body's tissues. Thereafter, its proliferation is controlled by its own internal agenda rather than the needs of the community of cells around it."

Curiosity, Weinberg says, rather than some "crusading desire to help humanity", drives his work, and it infects the book as well. It is curiosity about what happens at the sub-microscopic, invisible level inside cells, he says. It is the unravelling of a series of puzzles, and it is fun. Helping people "might be an almost inadvertent consequence". Cancer research did not have much cachet when Weinberg was cutting his teeth on molecular biology in the 1960s: he ended up working on a cancer virus simply because it was an interesting subject.

The book describes how cells, with genes as their common inner blueprint, read off particular instructions to choose different fates - to become muscle cells or blood or brain cells. They also take instructions on how to grow and divide, and when to stop growing. The particular genes that direct growth "take us straight to the heart of the cancer problem. They reveal the origin of cancer and will one day point the way to curing the disease."

As early as 1775, the London physician Percival Pott turned up evidence of chemicals that could trigger cancer - in his case, the creosote tars that stuck to the skin of young chimney sweeps, which produced scrotal cancers. But it was 200 years before researchers delivered the proof that DNA - the double helix that carries genetic information - directs cancer cells to grow uncontrollably. Each human cell they discovered, appeared to carry within it the seeds of its own destruction - latent cancer genes that could potentially be triggered by carcinogens, becoming oncogenes.

Like any major catastrophe, the growth of a nest of cancer cells also requires the disabling of a number of systems designed to prevent that growth - like the tumour suppressor genes, the self-destruct mechanisms for damaged cells and the "generational clock" that tells cells when to sicken and die. (Telomerase, the enzyme responsible for imparting unlimited growth to cancer cells, is the subject of Weinberg's current research.) Cancer can be the product of a one-two punch. Alcohol may not damage DNA directly, but high concentrations of drink kill many of the cells in the mouth and throat, and the survivors grow and divide. In the midst of duplication, they are more susceptible to damage from tobacco, a potent mutator of DNA. Cigarette smokers who drink face a thirty-fold increase in the risk of contracting cancer to the mouth and throat.

The book ends on a decidedly upbeat note. "We can glory in having lived while the foundations have been laidI We have lived through times of great excitement!" Weinberg concludes. Seeking to kill cancer cells without damage to healthy cells, researchers are working on creating antibodies that act as "smart bombs", guiding toxins to tumour-cell targets. They are looking for ways to trigger apoptosis, in other words, to induce cancer cells to commit suicide.

But diet may play a critical role in perhaps half of all human cancers. Just as sanitation and clean water have dramatically reduced disease, there's every indication that keeping down consumption of meat and animal fats in favour of healthier foods could sharply reduce the incidence of breast, colon and prostrate cancer. But the current spate of cancer diet books in the US, Weinberg cautions, are mostly in the business of "cynical manipulation" of cancer sufferers who are trying to retard the course of the disease. Diets can only be preventive.

It is a popular myth, he says, that the West faces a cancer epidemic. Mostly, we are just living longer, giving the disease more time to develop. In fact, our bodies are startlingly good at preventing cancer.

"We are very complicated organisms. We go through probably 1016 cell divisions in a life-time. Ten million billion times, cells divide. The potential for chaos, for a breakdown of order, is absolutely enormous. Consequently, to my mind it is a miracle we aren't covered with tumours all our lives."

One Renegade Cell: The Quest for the Origins of Cancer is published in the UK by Weidenfeld & Nicolson, Pounds 12.99.

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