Scientists Harnessing Body’s Natural Agents as Powerful Healers
Instead of the sharp edge of the scalpel or a massive blast of toxic chemicals to wipe out illness, doctors are turning to the body to heal itself.
They are taking the body’s natural products--hormones, antibodies, enzymes and even whole cells--to attack disease and restore normal functioning. Cancer, Parkinson’s disease, heart disorders and hormone deficiencies are all the targets of this new approach to treating illness.
Harnessing these new “natural” agents produced by the body might be called biological therapy, or biotherapy, much as toxic chemicals used to treat cancer are called chemotherapy.
It all started with the genetic-engineering revolution in the 1970s when scientists learned how to manipulate genes in the laboratory. Previously rare human proteins--interferon, interleukin-2, human insulin and human-growth factor--could suddenly be mass produced with these new gene-engineering techniques. Although the early experiments in human patients failed to live up to expectations, solid gains have been made and physicians remain optimistic about the role of biotherapies.
“In the next decade, the major advance will be genetic therapies,” said Bruce A. Chabner, director of the National Cancer Institute’s division of cancer treatment. Genetic manipulation, for example, is being increasingly studied as a way to fight diseases such as cancer and AIDS.
The idea of biotherapies has been around for decades, though the first ones were crude. Cow insulin, a protein essential for signaling cells to pull sugar from the blood, was discovered in the 1920s and injected into the bodies of diabetics.
Vaccination--the injection of a living but inactive virus or bacteria into the body--showed that it was possible to manipulate the body’s natural defenses. The immune system was programmed to prevent subsequent infection by that particular bacteria or virus.
Just before World War II, doctors discovered that blood could be transfused between individuals. And beginning in the 1960s came the organ transplants--heart, lungs, liver, pancreas, kidney, even bone marrow.
The common factor between these now standard treatments is that they use natural substances--cells in the transfusion, organs in the transplants, viruses in the vaccines, protein in the insulin. But they are limited. Blood doesn’t always match; organs are rejected; improperly prepared vaccines can cause the disease they were intended to prevent.
Most of the problems came from incomplete understanding of the biology. The new generation of biotherapies is changing that, putting in doctors’ hands some of the most powerful treatments ever developed. Biotherapies fall, generally, into three groups: proteins, genes and cells.
In the last five years, physicians have been putting to use the natural medicines produced for the first time by the biotechnology labs. Genetic engineers have learned to put specific human genes into bacteria, turning the bacteria into miniature factories that grow large quantities of the human proteins doctors can use against a certain disease. The new protein biotherapies include:
* Clot busters. Several natural proteins have been found that rapidly dissolve blood clots. Physicians now routinely inject these clot busters to stop heart attacks in mid-attack--something that never had been possible. Additionally, these drugs also have been used experimentally to stop strokes and open painful blockages in leg arteries.
* Blood boosters. A set of proteins has been found that stimulate the bone marrow to produce both red blood cells and certain types of white blood cells. Growing red blood cells is revolutionizing the care for end-stage renal failure, which causes the body to stop making blood. Before this discovery, these patients needed constant transfusions.
Stimulating white blood cells boosts immunity to various types of infections. It can prevent some of the secondary diseases associated with AIDS. Its most important use, however, may be the countering of the immune-destroying effects of cancer chemotherapy, thus allowing physicians to treat tumors with larger doses of the poisonous drugs and kill the cancer.
* Height control. Human-growth factor can literally add inches to children of short stature. They don’t always reach normal height, but they reach heights previously impossible. Some also have talked about using this powerful hormone for weight loss, and there have been reports of use by some athletes seeking an extra edge.
* Antibodies. The body’s immune system produces thousands of different-shaped proteins called antibodies that recognize invading bacteria and viruses by their shape--and then attack them. Scientists have learned how to make antibodies of any given type--called monoclonal antibodies--that can be used to diagnose disease both in the lab and in the body and can be used to attack cancer cells directly.
Organ transplants and blood transfusions have led the way in the use of living cells or tissues to treat an illness. But the new biotherapies take it all a quantum leap further.
* Brain transplants. Clearly the brain itself cannot be transplanted, but parts of the brain wear out for uncertain reasons. Parkinson’s disease arises with the loss of certain brains cells that produce a chemical needed for normal movement. Neurosurgeons have now experimented with transplanting into the brain patches of human cells that produce the missing chemical. Preliminary experiments with nerve cells taken from aborted fetuses reportedly show promise.
* Tissue transplants. In diabetes, pancreatic cells stop secreting the protein insulin. Although insulin can be injected every day, control of blood sugar is better when a pancreas is transplanted into the body. A number of human experiments are under way to inject just the insulin-making cells in the hope that they will work better and be easier to protect from rejection.
* Killing cancer. Researchers at the National Cancer Institute have found that certain white blood cells are primed to attack cancers. They remove those cells and stimulate them in the lab with a growth factor called interleukin-2. Once several billion of the white blood cells have grown in the lab, they are put back into the patient’s body and attack the tumor. More than half of the patients with the skin cancer malignant melanoma and with kidney cancer now respond to this treatment.
The third general form of biotherapy, genetic, relies on the recent ability to insert genes into cells of the body. Genes control the production of proteins, so gene transfers can be used to replace a missing protein permanently. This is the future of medicine, many believe. About 4,000 inherited diseases could be attacked by this technology.
* First steps. In the first gene transfer experiments in humans, begun last year at the National Institutes of Health, cancer researchers put a bacterial gene into the white blood cells they already had been turning into cancer killers. The gene allows them to track the altered blood cells in the body and to see which type best kills the cancer. Future experiments in which other genes are added should boost the cell’s cancer-killing power.
* Artificial organs. The biggest problem with gene therapy is getting the altered cells back into the body so that they survive. One approach under development in animals creates an artificial organ by growing the gene-modified cells on a synthetic pad that is surgically placed in the animal’s abdomen. Hormones are added that make blood vessels grow into the pad. Theoretically, the newly created organ could be designed to secrete any protein to treat a wide array of illnesses.
Although the new biotherapies have begun to radically alter the treatment of disease, they also have created controversies. For example, some of the tissue transplanted for diabetes and Parkinson’s comes from aborted fetuses. Groups opposed to abortion have so strongly opposed the use of this material that the government no longer funds any related research.
The debate will grow more intense as the massive project to identify and analyze every single human gene, now being developed at NIH, gets under way. It will speed the ability to detect diseases for which nothing can be done. That means doctors will be able to tell which patients are likely to get which diseases. Will patients want to know?
