FOLLOW-UP

An unproven weapon in the war on cancer

Scientists put a damper on high hopes for interferon

MICHAEL POSNER July 27 1981
FOLLOW-UP

An unproven weapon in the war on cancer

Scientists put a damper on high hopes for interferon

MICHAEL POSNER July 27 1981

An unproven weapon in the war on cancer

FOLLOW-UP

Scientists put a damper on high hopes for interferon

It was hailed as the wonder drug, the cure for every incurable illness, from cancer to the common cold. The hopes for interferon, however, were set too high; the death of Terry Fox last month was yet another illustration of its diminished promise. Fox’s osteogenic sarcoma did not react positively to interferon, administered during the terminal phase of his prolonged illness. “It has not lived up to its expectations,” confesses Charles Dahle, a spokesman for the American Cancer Society. “It does show some activity, but no greater than existing cancer treatments.”

That sober assessment is sharply at odds with the euphoria that greeted the earliest test results. Working with interferon that was only one-tenth of one per cent pure, scientists seemed to have scored dramatic success in shrinking or arresting the growth of various types of cancer. The results of secondary tests were statistically disappointing, however, and the medical world was forced to issue a hard reappraisal: pending further studies, it would be impossible to evaluate interferon’s place in the meagre arsenal of cancer treatments. The early optimism had been replaced—if not by pessimism, then certainly by a healthy realism.

Those studies are now going forward with a vengeance. Using both human interferon, a naturally occurring protein that seems to activate the body’s immunological system, and its genetically engineered facsimile, cancer researchers at half a dozen clinics in the U.S. want to render a conclusive verdict on the drug. Says Dr. Stephen Sherwin, head of one of seven trials sponsored by the National Cancer Institute (NCI): “We still feel it may ultimately have promise in treating some forms of cancer-lymphomas, breast cancer, multiple myelomas [primary tumors of the bone marrow]. But what I would stress is that we are still very much at the beginning of the process.”

The NCI experiments are initially aimed at determining whether the drug itself is safe to give to humans, and at what dosage. Although interferon was at first thought to be virtually free of hazards, the medical community has now concluded that there are some debilitating side effects—notably a kind

of malaise that saps energy. Researchers also speculate that, at some level, interferon does exactly the opposite of what it is meant to do; instead of putting the body’s disease-fighting mechanisms on alert, it seems to suppress them. “Perhaps,” says Dr. Thomas Dao, who is co-ordinating interferon trials at Roswell Park Memorial Institute in Buffalo, “the cause of earlier failures was the amount administered or the timing. We are years away from knowing what we need to know.”

But it is more than dosages and schedules that remain to be resolved. There are, it now appears, at least three major varieties of interferon—alpha, beta and gamma. The former two are relatively alike in composition, but the third contains quite different properties. Since the interferon given at the time of the earliest tests was so chemically impure, researchers aren’t sure what produced the positive reaction of the cancer, and what the side effects were. Even within the alpha family there are some eight or nine separate molecular species, each with distinct biological activity. It is a field of seemingly endless complexity.

Adds Dr. Thomas Merigan, who is overseeing four interferon studies at

Stanford University: “We also need to determine the optimum time for intervention. At what point is the interferon likely to be most active? The evidence so far is that the drug works best during early stages of the disease.” Some scientists believe that interferon’s greatest promise lies in the treatment of viruses, such as herpes, hepatitis, influenza and rabies. Among other experiments, Merigan recently concluded a five-year program testing interferon against chronic hepatitis B, a viral illness. He has now embarked on a five-year follow-up controlled study, involving 150 patients, to see if interferon—in combination with a second drug called Ara-AMP—promotes long-term improvements for carriers of the disease.

One problem experimenters no longer face is the acute shortage of interferon itself. Thanks to recent developments in gene-splicing and other technologies, volumes of interferon can be produced at a fraction of what it cost only two years ago. Natural interferon, collected from blood cells and other human tissues, once cost up to $150 for a daily injection. If interferon produced through gene-splicing goes into mass production, the cost could come down to as low as $1 a shot.

One researcher in the field of genetic engineering estimates that supplies of interferon will increase by 500 to 5,000

times by 1982. Because of scarcity and expense, fewer than 300 patients in the United States and 50 in Canada have been treated with interferon. The volume of testing has increased, but even if it grows by tenfold in the next 18 months, as experts have predicted, interferon will still reach fewer than one per cent of the cancer victims in Canada and the United States.

The largest test in Canada will take place in British Columbia, where an interferon purification plant is expected to open in eight months. The plant, financed by the Terry Fox Medical Research Foundation (using $22 million worth of shares in British Columbia Resources Investment Corp. as collateral), will purify partially processed lymphoblastoid interferon using technology supplied by the Wellcome Foundation of Britain. Wellcome has supplied an initial 32,000 megaunits of purified interferon to launch a test program of the B.C. Cancer Control agency involving 60 to 100 patients in the first year. The B.C. government investment involves a substantial risk since the drug is almost unproven and other companies in the field could beat Wellcome with better technology. Lymphoblastoid interferon is grown from the tissue cultures of white blood cells. This is an older technology than the better publicized genetic engineering in which the genes of common bacteria are altered or “spliced” to cause them to manufacture interferon. For the moment, the Wellcome technology is just as efficient and reliable, but gene-splicing is widely considered to be the wave of the future.

As greater quantities of interferon produced from gene-splicing become available, tests are under way to determine if this synthetic interferon is as effective as its natural counterpart. On the basis of tests conducted on a small number of patients at Stanford and elsewhere, Dr. Merigan tentatively concludes that the synthetic interferon does contain “the active principle.” But all of it, he stresses, “needs much more work before we can—unequivocally—be sure.”

It will take two to five years to solve the major mysteries. Says Dr. Hulbert Silver, who is in charge of the B.C. research program: “It is most unlikely that it is the wonder drug that will cure cancer. People get carried away with enthusiasm when they hear about interferon. The important thing from our point of view is that expectations not be inflated.” But no matter how hard scientists attempt to moderate expectations, interferon will remain a beacon of hope to those cancer victims who have no other.

MICHAEL POSNER

With files from Malcolm Gray, Diane Luckow and Nancy Wilson.