Dashed hopes and debate over 'cures’

JOHN BARBER February 2 1987

Dashed hopes and debate over 'cures’

JOHN BARBER February 2 1987

Dashed hopes and debate over 'cures’


Dr. Bernard Leibel, a senior diabetes researcher at the University of Toronto, finished an interview with one of the university’s public relations officers last October by saying, “Please don’t overplay this.” The university had arranged the interview to generate publicity about an experiment Leibel had conducted with Drs. Walter Zingg and Julio Martin, one which had succeeded in reversing diabetes in seven rats. And his comment reflected the team’s concern that the promise of that result not be exaggerated. But when university officials issued a press release on Jan. 5, the researchers said that their concerns had been realized. Articles about their discovery quickly appeared on the front page of newspapers across Canada, in many cases under headlines heralding a diabetes “breakthrough.”

That publicity enraged many scientists, who criticized the Toronto researchers for raising false hopes among diabetics. “It was awfully premature,” declared Dr. Marvin Bala, chairman of the Canadian Diabetes Association (CDA) research council. Added Bala: “It is astounding that this received the attention it did at such a preliminary stage.” The Toronto researchers were stung by the critical backlash from their peers, even though some prominent colleagues praised their work. For Leibel, 72, Bala’s attack was especially upsetting. Leibel, a former colleague of ' Sir Frederick Banting—whose 1921 discovery of insulin’s role in diabetes saved millions of lives—helped to found the CDA in 1952. He said that he is now considering resigning from the organization, and declared, “All my contemporaries are long retired and forgotten, and here am I, engaged in an unwelcome controversy over work that I consider the crowning achievement of my career.”

Other researchers have experienced similar brushes with controversy. In the fights against cancer and AIDS, even slight progress can create pres-

sure on researchers to announce their findings before submitting their work to the scrutiny of their fellow experts. As a result, many of them avoid using the term “breakthrough” as the search for cures intensifies. Still, several factors have made that conservative approach increasingly difficult. They include a growing interest in medicine on the part of the news media and the

public, competition among scientists for scarce research funds, and the emergence of a new genetic engineering industry, in which profits can hang on the development of new cures.

Perhaps the greatest pressure has been posed by the spreading scourge of AIDS—the terminal acquired immune deficiency syndrome. As victims demand information about, and access to, dozens of unproven drugs that could help them, they often raise an urgent issue: should people doomed to an early death be deprived of any treatment, however tenuous, because of scientific propriety?

The fight against diabetes has also been marked by decades of

failed promises. Regular injections of insulin can prolong diabetics’ lives by replacing supplies of a hormone they are unable to produce or assimilate naturally. But the substance cannot always prevent blindness and other complications or stave off premature death. As a result, much current diabetes research centres on restoring natural insulin production by trans-

planting pancreatic cells, called islets of Langerhans, that secrete the hormone. In order to do that successfully, the researchers must prevent immunological rejection of the transplanted islets.

To that end, Leibel, Zingg and Martin injected nine diabetic rats with increased daily doses of minced pancreas in the hope that the animals would become conditioned to the foreign tissue. In 1983, after a year’s preparation, they performed the transplants. The result: in seven of the nine animals the islets began functioning, and the diabetes disappeared. But to many scientists, the £ results did not justify i the ensuing publicity.

Declared Dr. Robert Ehrlich, head of pediatric endocrinology at Toronto’s Hospital for Sick Children: “I am not critical of the science—the results are clear. But I am critical of the fact that preliminary work on seven rats was released.”

For his part, the CDA’s Bala said that he was not aware that any scientific journal had published the Toronto team’s findings. In fact, the researchers’ findings were reported in the July, 1986, issue of the respected international journal Transplantation. Dr. Paul Lacy, a St. Louis, Mo., pathologist and world authority on islet transplantation, told Maclean's, “From a scientific point of view, it is a very interesting and a very important study.” He said that the experiment raised the prospect that young diabetics could eventually benefit from transplants without having to take antirejection drugs for the rest of their lives. Such drugs as cyclosporin can have severe side effects, and eliminating the need to use them is the “whole push” of much advanced diabetes research, according to Lacy.

A similar lifesaving quest—fuelled by optimistic press reports—is currently stirring controversy among U.S. cancer researchers. One year ago Dr. Steven Rosenberg of the U.S. National Cancer» Institute received worldwide acclaim for pioneering work on a new cancer treatment using Interleukin-2 (IL-2), a substance that the body’s immune system produces in small amounts. The results of his study were published in the highly respected New England Journal of Medicine. But last December, in an editorial in the Journal of the American Medical Association, Dr. Charles Moertel of the Rochester, Minn.-based Mayo Clinic accused Rosenberg’s team of creating a chaotic “media extravaganza” by wrongly describing their work as a breakthrough. He said that IL-2 had not produced high regression rates in cancer patients and added that the treatment’s cost was astronomical, in part because of the need to manage the “devastating toxic reactions” that it produces.

Rosenberg acknowledged that side effects from IL-2 can be severe. But he added that Moertel had overestimated them—and exaggerated the average cost of the treatment. And he denied ever using the word “breakthrough.” Indeed, the term first appeared in connection with his work in a cover story on IL-2 in the U.S. magazine Fortune, published shortly before Rosenberg’s findings appeared in the New England Journal. Rosenberg added that the widely read magazine’s story had “done a real disservice” to his team’s work and said that his team would soon publish an article in a scholarly

journal that “will resolve a lot of issues.” Still, he declined further comment until the article has appeared. Declared Rosenberg, echoing his own critics’ concerns: “I think it would be chaotic if information were to appear in the lay press before undergoing peer review.”

In fact, many reporters delay publicizing medical developments until a scientific review confirms their promise. At the same time, some journalists argue that the time needed for painstaking reviews of research designed to relieve suffering can add to victims’ distress. In one case, a March, 1985,

issue of the New England Journal reported on a study of breast cancer treatments. The study, which began in 1976, concluded that removal of tumors alone was just as effective as mastectomy. That surgical procedure—which until recently was standard treatment—excised an entire breast. But the journal did not publish the study until one year after researchers had submitted their findings. The reason: the report’s reviewers wanted to see the effects of treatment over a longer time-period. But, concluded a 1985 editorial in The Wall Street Journal, which criticized the delay, “some 50,000 women had their breasts cut off after the leading researchers decided this procedure most likely was not necessary.”

More recently, the AIDS epidemic has increased pressure on researchers

to release news of potential weapons against the disease. Earlier this year officials of Costa Mesa, Calif.-based ICN Pharmaceuticals Inc. released favorable test results of the company’s patented anti-AIDS drug, Virazole. Company spokesmen maintained that their tests had proved the drug’s effectiveness against AIDS-related complex-symptoms similar to AIDS that often develop into the disease. But other researchers remained skeptical. For one thing, ICN researchers have not yet submitted their findings to a scholarly journal. Instead, the company has asked’ U.S. government officials to

make the drug available to victims without further testing.

Still, for Margaret Somerville, director of the McGill Centre for Medicine, Ethics and Law in Montreal, the current controversies over Vi razóle and other unproven drugs to treat terminal diseases are unwarranted. Said Somerville: “AIDS patients are all going to die anyway. Why shouldn’t they get these drugs?” Yet Somerville acknowledges the hope the general public harbors that scientists will conquer cancer and other incurable diseases. Said Somerville: “To some extent, medicine has replaced religion in our society. People expect miracles.” And some new developments will continue to be hailed as breakthroughs—regardless of how much the term annoys and alarms researchers.

— JOHN BARBER in Toronto