Announcements of genetic discoveries are hitting the headlines so quickly, one researcher says, that scientists are learning of genetic breakthroughs from the mass media rather than in scientific literature.
The discoveries are coming so fast, another scientist notes, that we're now reading about "the gene of the week" in the news.
However you hear it, reports that this or that gene has been located or reproduced in the laboratory reflect stunning accomplishments. Scientists doing gene research confront the following: the 46 human chromosomes inside every cell are believed to contain 50,000 to 100,000 genes. And a single gene can consist of millions of units, called bases.
So pinpointing the gene responsible for a particular illness is, researchers often say, like finding the proverbial needle in the proverbial haystack.
Dr. Irving Gottesman, professor of psychology at the University of Virginia at Charlottesville, is one of several scientists sifting through that haystack for the genetic roots of schizophrenia. What's the chance he'll find it?
"Like winning the Virginia lottery," he answers. "Not zero, but not real high either. But people keep buying lottery tickets, and somebody wins, even though the odds are against them."
But while headlines suggest that what's won is hope of quick mastery over genetic disease, scientists are generally more restrained about the immediate practical impact.
"This knowledge has the potential for many different kinds of uses and applications," says Dr. Scott Diehl, professor of genetics and psychiatry at the Medical College of Virginia in Richmond.
"But I think we have to be very cautious about promising too quick a return. Having the gene in hand gives a basic knowledge of the fundamental cause of disease, but it doesn't tell you how the gene works -- what it does or fails to do that causes the disease."
In fact, scientists do understand a little about how the genes work:
They direct the cells to produce particular proteins or components of proteins; and somehow they "know" when and where to do that. Although the genes in every cell of the body are the same, they don't all work in all cells.
In brain cells, only those involved in proteins appropriate to the brain are active; in eye or bone or skin or muscle cells, the same is true.
When scientists "find" a gene, what they've usually got are the parts that order up the proteins; they don't necessarily have the "regulatory sequences" that turn it on and off, explains Dr. Maimon Cohen, chief of the division of genetics at the University of Maryland Medical Center.
And while finding the gene is an important first step, the real key to mastery of genetic disease is finding and learning to manipulate the regulatory mechanism.
Think of the gene as a car, Dr. Cohen suggests. "You know the structure, you know what it looks like. But if you don't have the key to turn it on, that car isn't going to be any good to you. Operating the accelerator, the gears, the brakes -- that's the regulation. These other [regulatory] sequences determine the tissues the gene works in, the rate at which it works, all sorts of other things."
If a gene or its regulatory mechanism is abnormal, the protein-making instructions will also go awry. The proper protein won't be made at the proper time; the tissues that require it won't develop, function, or renew themselves as they should.
And in a cascade of events like those in the adage that begins with the loss of a horseshoe nail and ends with the loss of a kingdom, the individual can be sick or disabled, or even die.
But many diseases don't seem to follow from a single faulty gene or protein. Although scientists believe that such common disorders as heart disease, cancer and mental illness have genetic roots, they also think the outcome is the cumulative impact of several faulty genes plus, in some cases, an environmental trigger -- anything from prenatal accident to poor nutrition to emotional stress.
"Huntington's disease is a pure genetic disorder: If you get the gene, you get the illness. Cystic fibrosis is that way too," says Dr. Wade Berrettini, staff psychiatrist at the National Institute of Mental Health.
But manic depressive illness, his own area of research, is different.
"It's in part genetic, but not a pure genetic disease," he says. "In identical twin pairs [who have identical genes], if one twin has it the other does as well in 65 percent of cases. But it's difficult to understand the other 35 percent if it's a perfectly genetic disease. So there may be environmental or other factors that are protective, since it's possible to inherit the gene without getting the disease."
The same complexity hampers the search for a schizophrenia gene.
"Clinically, people are diagnosed as schizophrenic, but there are probably multiple underlying diseases," says Dr. Diehl. "I would be very surprised if we found schizophrenia was caused by a single gene. Our hope is that there is a manageable number of genes. Where it really falls, between a few genes and 100, remains to be determined."
Even for diseases that can be traced to one abnormal gene, knowing where to find it is not the same thing as knowing how to fix it.
"The most obvious way the information has been used is for better diagnosis, but it is many orders of magnitude simpler to that application than it is to treatment," says Dr. Reed Pyeritz, professor of medicine and clinical director of the Center for Human Genetics at the Johns Hopkins Medical Institutions.
"The potential for therapy will depend on the nature of the defect," says Dr. Diehl. "If schizophrenia turns out to be that something goes wrong in the formation of the brain in the embryo or very early life, we may not be able to fix that in the adult schizophrenic, where everything is already wired in. If some cases turn out to be not so much in the structure as in the chemical balance, that type of thing is more amenable to intervention."
Nevertheless, what's known so far about genes and their regulation is beginning to have some impact on disease. Last week, scientists announced the start of a gene therapy experiment aimed at correcting a child's genetically defective immune system. A similar effort may soon be launched for treatment of skin cancer. Correction of hemophilia, through gene therapy, has already been tried in dogs.
And last June, doctors announced a successful transplant of cells containing normal genetic instructions into the toe muscle of a boy with muscular dystrophy. Within three months, the toe appeared stronger, and a biopsy showed that the transplanted cells were manufacturing the protein missing in muscular dystrophy.
"If it works, how it could be scaled up to the entire patient is still mind-boggling," Dr. Pyeritz warns.
"The skeletal muscle in the big toe is very different from heart muscle. Both are abnormal in muscular dystrophy. That's how it is with many hereditary disorders. Many organs are affected, and even if you can replace the gene in one tissue, that won't solve the patient's problems."
However, with the accumulated knowledge of genetics already at critical mass, the explosion of new knowledge and new techniques does hold new hope for conquest of disease and disability.
"I think, in 20 years, it will be possible to do some sort of genetic screening of an individual to find out what some of their inherited susceptibilities are to common disorders -- some different forms of cancer, atherosclerosis, heart disease, neurologic disorders like Alzheimer's disease -- and we will be able to do a lot of pre-symptomatic detection," Dr. Pyeritz says.
But the possibilities of detecting such late-blooming diseases raise further social and ethical questions.
"What do you do if you identify pre-natally a person with the schizophrenia trait?" asks Dr. Gottesman. "Do you abort, or have prenatal intervention? What about insurance, and jobs? How will it influence the way you treat those people? Do you want them to run for president?"
"I hope in 20 years, the social, ethical, legal and psychological ramificationms will be debated, and a consensus reached," Dr. Pyeritz says. "That, to me, is as important as the science."
Chromosome: One long strand of double-helix DNA. Each cell in the body contains 46 chromosomes. One chromosome in each pair comes from the mother, and the other comes from the father.
DNA: A chemical (Deoxyribonucleic Acid) that is the basis oheredity.
Gene: Hereditary instructions, consisting of many units called "bases," which order the cells to manufacture proteins or components of proteins.
Genetic engineering: Use of enzymes to cut out segments oDNA and splice them into a strand in another cell or organism.
Gene therapy: Treatment of disease by injection of normal, genetically engineered copies of a defective gene.
Inherited disorders: About 400 diseases are genetically linked or believed to be, including alcoholism, arthritis, certain cancers, cystic fibrosis, diabetes, Duchenne muscular dystrophy, eating disorders, hemophilia, high cholesterol, Huntington's disease, manic-depressive illness, neurofibromatosis, obsessive-compulsive illness, schizophrenia, sickle cell anemia, Tourette's Syndrome and Tay-Sachs Disease.
For more information, read:
*"Genome." By Jerry E. Bishop and Michael Waldholz (Simon & Schuster, 1990).
*"The Telltale Gene," Consumer Reports magazine, July, 1990.
The Gene Hunt," Time magazine, March 20, 1989.