Subject: (A Special Report): Biotech Boom Date: Published: 11/13/89 (237 lines) Source: Wall Street Journal. Copyright Dow Jones & Co. Inc. Technology (A Special Report): Biotech Boom --- Medical Mimics: Drugs That Regulate the Body's Healing And Growth Processes Open a New Frontier ---- By Sue Shellenbarger FOR JILL JONES, life before the age of biotechnology was an endless round of illnesses. The Brighton, Mich., teen-ager has a rare, life-threatening blood disorder called neutropenia, a shortage of infection-fighting white blood cells. The little ailments of daily life -- colds, sore throats, ear infections -- could send her to the hospital. At times, her mouth sores were so painful that she couldn't eat. She tried attending college but left after a few months; sickness struck so often that continuing was pointless. Then in February, Ms. Jones was chosen to take part in experiments with a new bioengineered drug aimed at bolstering her body's natural defenses. Her father wept. Now, after several months on the drug, Ms. Jones, 19, is leading a life approaching that of a normal teen-ager. She can at last focus on the little pleasures of daily life -- a trip out of town with a friend, a night of dancing. She is once again planning to enroll in college. For the first time in years, she says, "I have felt really good. It's wonderful." Ms. Jones is a pioneer on biotechnology's hottest new frontier: the development of man-made "growth factors," drugs that mimic the body's natural proteins that regulate the growth and healing processes of cells. For years, scientists have known about the powerful role played by these scarce proteins. Now biotechnology's ability to produce them holds out the promise of a medical revolution. Already, scientists are testing growth factors on humans in hopes of treating ulcers, burns, broken bones, and the often-devastating side effects of cancer and AIDS treatments. Others hope growth factors will one day reverse some of the chronic degenerative ailments of old age, including heart disease, arthritis and osteoporosis. "We're seeing the real fruits of the biotechnology revolution," says Jerome Groopman a leader in testing growth factors at Boston's New England Deaconess Hospital. "It really is a new era in medicine." The growing availability of the potent proteins, adds Andrew Baird, a biochemist at the Whittier Institute for Diabetes and Endocrinology at La Jolla, Calif., means that "we can seriously sit down and think of things that existed only in science fiction before." The new era, however, is just dawning; most of the drugs are still years from the market. Only one of the new growth factors -- erythropoietin, or EPO, which stimulates production of red blood cells -- has been approved by the Food and Drug Administration for routine use in patients. Other blood-stimulating substances, including Neupogen, the Amgen Inc. drug that is being taken by Ms. Jones, are still in clinical trials. Human tests of bone-growth substances are just beginning, and nerve growth factors are still in early animal trials. Moreover, it isn't clear yet that scientists can make broad improvements in the body's natural responses to disease, injury and aging. The blood-cell stimulators are by far the simplest growth factors. The healing process in other tissues, such as skin, bones and nerves, is much more complex. "There are a lot of hurdles to be met," says the Whittier Institute's Dr. Baird. Researchers need a better understanding of the growth factors' role in causing or preventing cancer, for instance, before they can eliminate the risk that they will spin out of control. The growth-factor boom also raises a serious cost issue: Many of these drugs would have to be taken repeatedly -- some for life -- and the expense may be enormous. Clearly, though, the drugs already have the ability to vastly improve the quality of life for many people. Consider EPO. The drug, which analysts estimate will have sales of more than $500 million within a few years, cures anemia in some patients and eliminates in others the need for blood transfusions. For years, John Cole, a Lorain, Ohio, newspaper editor with kidney disease, suffered worsening anemia caused by regular dialysis treatments. He needed weekly transfusions that haunted him with the fear of contracting AIDS, and he felt so drained that he could barely drag himself to work. "Taking out the trash was a major undertaking," he says; a walk on the beach with his wife was out of the question. After 2 1/2 years on EPO, Mr. Cole, 40, no longer needs transfusions, his anemia is under control and he works out three times a week. "I feel tremendous," he says. EPO also is expected to help patients store their own blood in anticipation of surgery by raising their bodies' red blood-cell production. Teena L. Lerner, the biotechnology analyst at Shearson Lehman Hutton Inc., estimates that EPO could reduce the need for transfusions from others by 20% by 1993. Close behind in clinical trials are white-cell stimulators, including Neupogen and related products under development by Genetics Institute Inc., Cambridge, Mass., and Immunex Corp., Seattle, in marketing partnerships with pharmaceutical firms. The substances seem certain to improve survival prospects for some cancer patients. While chemotherapy effectively kills cancer cells, it also kills the bone marrow that produces infection-fighting white-blood cells, forcing doctors to reduce or halt chemotherapy treatments. Only an estimated 20% of the one million patients who undergo chemotherapy each year receive the full prescribed, or target, amount. The blood-cell growth factors can combat the toxic side effects, some clinical trials show, helping to restore the white cells to normal levels after chemotherapy. That significantly reduces the risk of infection and frees the physician to administer target doses of chemotherapy. "It's exciting," says Jeffrey Crawford, who has seen the drug improve the condition of lung-cancer patients undergoing chemotherapy in clinical trials at Duke University Medical Center and the Durham, N. C., Veterans Administration Medical Center. "It takes away some of the obstacles we've had, in terms of what we can do for patients." Another white-cell stimulating factor nearly doubled the short-term survival rate of cancer patients who had rejected transplanted bone marrow, a common and often fatal event following chemotherapy or radiation treatments for cancer. The drug has also been shown to bolster white-cell levels in patients with AIDS, enabling some to tolerate treatment with the antiviral drug AZT. Other growth factors show promise in healing wounds. More than 60 papers on such growth factors have been published in the past five years, according to the New England Journal of Medicine. The growing availability of the proteins "has swept aside medicine's traditionally cautious attitude toward the acceleration of healing," the Journal said in a recent editorial. In one test with burn patients, a skin-healing agent called epidermal growth factor shortened by about a day and a half the time needed to heal wounds created in skin-grafting operations. Chiron Corp. of Emeryville, Calif., will soon begin testing EGF for healing eye tissue after cataract surgery. Chiron is testing EGF for treating severe stomach ulcers. Scientists are also in hot pursuit of substances designed to heal or rebuild bone. International Genetic Engineering Inc., Santa Monica, Calif., is beginning human trials of a bone-growth substance it calls osteogenic factor. In animal experiments, the protein helped repair cranial and limb injuries in rats and rabbits in three to five weeks. Eventually, the substance might be used to repair severe limb fractures, deformed cranial and facial bones, or jawbones damaged by periodontal disease, says Arup Sen, executive vice president of International Genetic Engineering. The research is increasingly ambitious, focusing on broad-acting, more complex growth factors that affect more than one kind of tissue or even the entire metabolism. Genentech Inc. has begun human trials of a highly active protein, insulin-like growth factor I, for a condition called wasting syndrome, in which seriously ill or injured patients begin to lose lean muscle tissue and their ability to use the food they eat. Chiron has begun testing the same substance for use in treating osteoporosis, a thinning of bones. "You're talking about an area of molecular biology that's moving at an incredible pace," says Paul Reier, a neuroscientist at the University of Florida in Gainesville. Progress, though, has a price. Epogen, Amgen's brand name for EPO, costs about $4,000 to $8,000 a year, depending on the patient's weight. While Neupogen hasn't been priced yet, some patients are already worried about the cost. "You're not going to see low-priced drugs coming out of this research," says Shearson's Ms. Lerner. The field also presents some novel hurdles for medical science. For instance, blood growth factors can easily be injected, and bandages, gels and lotions can be used to hold wound-healing agents in place. But applying the substances to bones or nerves is a far more difficult matter. "The big problem with growth-factor biology today is delivery," says Dr. Baird of the Whittier Institute. Bruce Pharriss, senior vice president, science and technology, for Collagen Corp., a Palo Alto, Calif., biotechnology concern, adds, "We have to find a way to have the stuff in high concentrations in the tissues that need it, and low concentration in those that don't." Many growth factors are dizzyingly complex, raising further concerns about unforeseen side effects. Many play multiple roles in the body. One promising agent called fibroblast growth factor, for instance, prevents the death of nerve cells in laboratory cultures as well as stimulates healing of cartilage in animal experiments. Other growth factors react differently in different settings. One protein, called transforming growth factor beta, retards capillary growth in the laboratory but stimulates it in laboratory animals. The factors "are like symbols of the alphabet. They mean one thing in one context and something else in another," says Michael B. Sporn, a leading growth-factor researcher at the National Cancer Institute. Some of the substances have had startling side effects in clinical trials; one blood growth factor unexpectedly reduced cholesterol levels in patients. Eventually, such unforeseen effects "may lead to new therapeutic ideas," Marcus Reidenberg, a Cornell University Medical Center physician, wrote in a recent issue of the Journal of the American Medical Association. There's evidence, for instance, that some of the blood-cell factors play a role in causing leukemia; researchers hope to harness them in a way that will reverse the disease. For heart-attack victims, applying a growth factor to damaged cardiac tissue following a heart attack might help the organ repair itself, Dr. Sporn suggests. The same factor is believed to curb the body's immune resonses under some circumstances, raising hopes that it might be used to treat such chronic inflammatory diseases as rheumatoid arthritis. Neurologists are peering still further on the growth-factor frontier, setting their sights on spinal-cord or brain-tissue repair. Jerry Silver, a neuroscientist at Case Western Reserve University in Cleveland, has had some success in restoring severed nerves in rats and cats by implanting nerve tissue from embryos; other scientists are claiming success in working with nerve growth factor, a protein found in many parts of the nervous system, to regenerate damaged tissue. "I think there's hope" that eventually, "we can cure spinal-cord injury or massive stroke" victims, Dr. Silver says. Ultimately, scientists may seek to regulate every cell of the body, yielding "a vast array of products, most of which probably haven't been discovered yet," says David Stone, a spokesman for Genetics Institute. The field, he says, "represents a large part of the potential of biotechnology." --- Ms. Shellenbarger is a staff reporter in The Wall Street Journal's Chicago bureau. 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