The American Spectator

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The desire to start over with a "cancer genome project" tells you they know they are not even at first base. Dr. Harold Varmus, now president of the Memorial Sloan-Kettering Cancer Center in New York, told the Times in March that the new project could "completely change how we approach cancer."

Completely change? Maybe we do need a complete change. What about his decades-old Nobel work? Was that a waste? In a way I think it was worse than that, because when an erroneous theory is rewarded with the top prize in science, abandoning that theory is difficult. The backtracking required is an embarrassment to all.

JOURNALISM PLAYS A CRUCIAL ROLE. Especially in the field of medical science, there is a big problem. It exists at all major newspapers and I don't mean to single out the New York Times. Science journalists don't see themselves as qualified to challenge the experts. If a reporter were to do so, quoting non-approved scientists, top-echelon NIH officials would surely complain to editors, and the reporter would be reassigned. The nation's health would be said to be endangered.

All this contrasts with the far greater freedom that journalists enjoy in the political arena, including defense and foreign policy. About 35 years ago, leading newspaper editors decided to chart their own course and form their own judgments. The context was the Vietnam War, more specifically the Pentagon Papers. A big report critical of U.S. policy was leaked to the press, and the Nixon administration went to great pains to suppress it. National security was invoked, judicial restraining orders were issued, but eventually the "public's right to know" trumped "national security." The material was published.

That was the background from which Woodward and Bernstein and the Watergate investigation emerged a year later. And we were the better off for it. The real danger, then and now, was that of unchecked government power. And we are seeing that exercised in the realm of medical science, where we do not have a press that dares to think independently.

HOW DID THE IDEA TAKE ROOT that gene mutations cause cancer? Well, in the 1920s researchers bombarded fruit flies with X-rays and mutant flies resulted. Humans exposed to large X-ray doses a hundred years ago proved to be at high risk for skin cancer and leukemia. It was convincingly shown that X-rays produced both mutations and cancers.

Working at the NIH in the 1960s, the biochemist Bruce Ames used bacteria to detect the mutagenic properties of various substances. Some carcinogens proved to be mutagenic, hence the gene-mutation theory of cancer. Robert A. Weinberg, who directs a cancer research lab at MIT, says that by the 1970s he and others had come to believe that "Ames was preaching a great and simple lesson" about carcinogens: "Carcinogens are mutagens."

Some are, but some of the best known are not. Neither asbestos nor coal tar, found in cigarettes, are mutagenic. They are carcinogens but they don't affect the DNA -- the genes. But there was one more crucial discovery still to be made. Or rather, rediscovery.

Robert Weinberg later claimed that a mutation in a single gene indeed had transformed a cell in vitro. But it turned out that the cell-line, one that had been provided by the NIH, was already "immortal," or cancerous. It did not have the right number of chromosomes.

Normal cells have 46 chromosomes -- 23 each from mother and father. Such cells are "diploid," because their complement of chromosomes is doubled. In case you never took biology, genes are segments of DNA strung along the chromosomes. The largest chromosomes, such as Chromosome 1 or 2, include several thousand genes each. Sometimes babies are born with one extra copy of the smallest chromosome, and because it is in the germ line this defect is in every cell of the body. Such babies have Down syndrome. Having an extra chromosome is serious business.

Here is the key point: cancer cells do not have the correct complement of chromosomes. Their "ploidy" is not good, so they are said to be aneuploid. Cancer cells are aneuploid. This defect arises not in the germ line, but in the grown body. Cells divide in the course of life, by a process called mitosis, and sometimes there is an error in the division. The chromosomes do not "segregate" properly (do not end up equally in the two daughter cells) and an extra chromosome may be hauled off into one of the new cells. Such over-burdened cells will usually die, but sometimes the error repeats and magnifies and increases. The cell just keeps on dividing, its control mechanisms overridden by the abundance of extra DNA in the cell. A tumor forms in that part of the body, and that is cancer. Some cancer cells may have as many as 80 chromosomes instead of 46. They may actually have double the right number of genes.

The aneuploid character of cancer cells is the first thing that Theodor Boveri and others noticed when they began to look at cancer under the microscope, 100 years ago. Leaving unresolved the question of what causes aneuploidy, early researchers thought that this was surely the genetic cause of cancer. Mutation didn't enter into it. But gradually the early research was buried. In the last generation, textbooks on the cell and even textbooks on cancer have failed to mention aneuploidy or its bizarre chromosomal combinations. Weinberg wrote two books on cancer without mentioning aneuploidy. Overlooking what was plainly visible in the microscope, researchers worked for years with those defective, immortalized cell lines, assuming that their extra chromosomes were unimportant.

An analogy suggests the magnitude of the error. Cells today are compared to factories, so let's think of an automobile plant. A cancer cell is the equivalent of a monster car with (let's say) five wheels, two engines, and no brakes. Start it running and you can't stop the damned thing. It's hazardous to the community. The CEO wants to know what's gone wrong so he sends underlings into the factory. There they find that instead of the anticipated 46 assembly lines, there are as many as 80. At the end of the process this weird machine gets bolted together and ploughs its way out the factory door.

But today's gene mutation theorist is someone who says: "That's not it. The extra assembly lines are irrelevant. What is happening is that three or four of the tens of thousands of workers along the assembly lines are not working right!" In the analogy, genes along the chromosomes correspond to workers along the assembly lines.

Any CEO would fire the lunatic who thought a few errant workers, and not the bizarre factory layout, had caused the mayhem. But in the realm of cancer research, those who do say that are rewarded with fat grants, top posts, and awards. That's a measure of what has happened to cancer research.

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