HEALTH MATTERS : A GENETICIST´S CANCER CRUSADE / THE WALL STREET JOURNAL WEEKEND INTERVIEW ( HIGHLY RECOMMENDED READING )

THE WEEKEND INTERVIEW

NOVEMBER 27, 2010.

A Geneticist's Cancer Crusade


The discoverer of the double-helix says the disease can be cured in his lifetime. He's 82.
By ALLYSIA FINLEY

'We should cure cancer," James Watson declares in a huff, and "we should have the courage to say that we can really do it." He adds a warning: "If we say we can't do it, we will create an atmosphere where we just let the FDA keep testing going so pitifully."


The man who discovered the double helix and gave birth to the field of modern genetics is now 82 years old. But he's not close to done with his life's work. He wants to win "the war on cancer," and thinks it can be won a whole lot faster than most cancer researchers or bureaucrats believe is possible.


Call it the last crusade of one of the nation's most indefatigable and productive scientists. In a long career, Dr. Watson was awarded the Nobel Prize in Physiology or Medicine (1962), garnered 36 honorary degrees and wrote 11 books, including the bestseller "The Double Helix" (1968), which recounts his dramatic quest with Francis Crick to determine the structure of DNA. He spent the early 1990s helping spearhead and direct the Human Genome Project to identify all human genes. And there's the 40 years he's devoted to transforming the Cold Spring Harbor Laboratory in Long Island, N.Y., from a ramshackle ruin into the elite cancer research institute it is today.


To hear Dr. Watson tell it, this determination began—at least formally—in Hyde Park at the age of 15. "The University of Chicago always used to be ranked in the U.S. News and World Report as the third most unpleasant college to go to in the United States," he chuckles. "It was a place that was knocking you down and expecting you to get up by yourself. Nobody was picking you up."


He says he's the better for it because it taught him how to be a leader, something he thinks there are too few of nowadays. "The United States is suffering from a massive lack of leadership. There are some very exceptional, good leaders. I'm not saying they don't exist, but to be a good leader you generally have to ruffle feathers," which Dr. Watson believes most people aren't willing to do.


He certainly is. Throughout his career, Dr. Watson has been a lightning rod for controversy, beginning with his unflattering portrayal of some fellow scientists as awkward and hostile in "The Double Helix." He later butted heads with fellow genetic researcher and founder of Celera Genomics, Craig Venter, over the commercialization of the human genome. Dr. Venter wanted to turn a buck for his firm by selling access to the human genome sequence. Dr. Watson thought the human genome database should be free to the public.


In 2003, Dr. Watson stirred up another academic kerfuffle when he joked that genetic engineering could be used to make all women beautiful and, more seriously, that gene therapy could one day cure stupidity. His 2007 book "Avoid Boring People: Lessons from a Life in Science" used the following words to describe former Harvard colleagues: "dinosaurs," "vapid," "mediocre" and "deadbeats."


But these days, Dr. Watson is sparring with the bureaucratic behemoth known as the FDA.


"The FDA has so many regulations," Dr. Watson says. "They don't want you to try a new thing if there's an old thing that might work. . . . So you take the old thing, but we know cancer changes over time and we would really like to get it whacked early, and not late. But the regulations are saying you can't do these things until we give you a lot of s— drugs," he snorts. "Shouldn't this be the patient's choice to say I would rather beat the odds with a total cure rather than just to know that I am going to have all my hair fall out and then after a year I'm dead? . . . Why should [FDA commissioner] Margaret Hamburg hold things up? There's the cynical answer it gives employment to lawyers."


Ah, the lawyers. "Right now America is being destroyed by its lawyers! Most of the people in Congress just want work for lawyers." He quickly adds: "I was born an Irish Democrat, so I wasn't born into a family which instinctively says these things. But my desire is to cure cancer. That's my only desire."


Dr. Watson may have been born an Irish Democrat, but he's more of a libertarian when it comes to scientific regulation. In his view, freer research enables greater innovation. "I do think one success of Northern Europe, which the United States came from, was its willingness to accept innovation in business practices like Adam Smith and the whole Enlightenment. It essentially made the merchant class free instead of controlled by the king and aristocracy. That was essential."


Another impediment to innovation today is funding. Dr. Watson thinks money is being spread around too much and not enough is going to the best brains. "Great wealth could make an enormous difference over the next decade if they sensibly support the scientific elite. Just the elite. Because the elite makes most of the progress," he says. "You should worry about people who produce really novel inventions, not pedantic hacks."


He also complains that too often government and private money help support scientists rather than cutting-edge science. "That's not the aim of our money—job research, job security. It should be job insecurity. Or hospital insecurity. Empty the breast cancer ward."


Dr. Watson's commitment to innovation is why most scientists at Cold Spring Harbor don't have tenure. Instead, they have security for five years. "We can't decide at the age of 40 that you're going to have a job for 30 years even though you're not producing much science."


Although Dr. Watson says leaders should think in the long term, he is critical of those who say we might find a cure for cancer in another 10 to 20 years. "If you say we can get somewhere in 10 to 20 years, there's no reason you shouldn't be saying 20 to 40, except then people would just give up hope. So 10 to 20 still maintains hope, but why not five to 10?" He adds that there's no reason we shouldn't know all of the genetic causes of major cancers in another few years.


"I want to see cancer cured in my lifetime. It might be. I would define cancer cured as instead of only 100,000 being saved by what we do today, only 100,000 people die. We shift the balance." Alas, modern research has merely reduced cancer mortality in the United States from about 700,000 per year to about 600,000. "We've still got 600,000, which is what the problem is."


The challenge now—at least by Dr. Watson's lights—is killing the mesenchymal cells that cause terminal cancer and figuring out why those cells have become chemotherapy-resistant. He says scientists and doctors are reluctant to tackle terminal cancer because there's so much that remains uncertain about its causes.


The treatment of early-stage cancer, however, is more certain since scientists have already pinpointed many of the genes that are associated with specific cancers. But they still don't know exactly which gene or gene mutations lead to terminal cancer.

Dr. Watson points out that scientists are correctly looking at DNA before they treat early-stage cancer, since different drugs work on different genes. "If I had cancer I'd certainly want them to look at the DNA to see if there's a Ras gene or change in the Ras gene," which signals cell growth and proliferation.


He points to lung cancer as a case in point. Right now Dr. Watson says there are two types of treatments. The first is a new drug that treats cancers linked with the specific gene ALK, which has proven effective in trials. "I have no idea if it works beyond the first six months, but most drugs don't work in the first six months, so that's very good."


Then there's Tarceva and Iressa, two drugs that inhibit the epidermal growth factor receptor that causes cancer cells to divide. But "they only work on about 10% of people," who have specific mutations in their tumors. "And they work for about a year, and then you become resistant. And we don't have anything to treat the resistant cancer with."


So this is where we now stand in the war against cancer: at our own 20-yard line with a playbook full of untested, complicated plays. But Dr. Watson is optimistic that there could be a Hail Mary: a single drug that will work on all of the deadly mesenchymal cells. All of these cells, he notes, secrete a protein—interleukin-6—and in lab experiments, adding interleukin-6 to lung cancer cells that had been controlled by anti-cancer drugs made them resistant to the treatments.


Thus the key to curing cancer may be finding a drug that blocks interleukin-6. "While this would be wonderful if it turns out to be true," he says, he doesn't know if it is and he concedes, "it's not conventional wisdom."


Despite his crusade, it's not cancer that personally scares Dr. Watson. It's Alzheimer's disease. When he had his genome sequenced and published in 2007, he specifically asked that the doctors not reveal whether he had a gene that would make it virtually certain he would develop Alzheimer's. The mentally debilitating disease would make it impossible for him to continue his research—not to mention that it would estrange him from his family.


I ask Dr. Watson about the double-edged sword of DNA testing and its proliferation. As prices fall due to improved technology, the market for testing grows. Now companies like 23andMe are selling personal DNA tests for roughly $500. Simply spit in a tube, send it in, and in a few weeks you'll get back everything you've ever wanted to know about your genetic inheritance—and some stuff you'd probably rather not.


While such information might encourage some people to adopt healthier lifestyles or get more frequent check-ups, it could also cause undue anxiety. For example, what do you do when you learn at the age of 20 that you have a gene that makes you susceptible to Parkinson's disease—something that you can't do anything about?


To this question, Dr. Watson says that DNA testing "has to involve a lot of acquired common sense." But he doesn't think that common sense should come from government agencies. "I don't see how regulations can do it." Banning it because of potential negative repercussions would be futile.


Futile—now that's a word you won't often hear Dr. Watson use. "I'm going to look optimistically and of course sometimes it doesn't work," he says. But "you move forward through knowledge. You prevail through knowledge. I love the word prevail. Prevail!"


Ms. Finley is assistant editor of OpinionJournal.com.


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