THANKS TO INCREDIBLY rapid advances in biotechnology during the last few years, scientists may soon be able to decipher health secrets long locked in the genetic code and foretell what diseases people are likely to get.
Within 10 to 15 years, some scientists expect, a kind of ”genetic fingerprinting” will become routine–providing each individual with a potential disease profile. People could then eliminate from their lives those factors thought to trigger particular ailments.
Modern medicine underwent its first big revolution in the middle of the 19th Century when Louis Pasteur proved the germ theory of disease. Infections, until then a mystery, were shown to be caused by invading organisms too small to be seen except with a microscope.
Today, we are on the threshold of an equally momentous revolution–one almost unthinkable only a few years ago–as medicine develops the ability to decipher the genetic code in each person and begins to read therein the clues that signal predisposition to certain ailments.
Scientists have for some time suspected a link between genes and disease, but they have only recently begun to acquire the ability to link some ailments to specific genes.
A major breakthrough occurred in June, when researchers at the California Institute of Technology unveiled the first automatic DNA sequencer. DNA
–deoxyribonucleic acid–is the component of living matter that contains the genetic code.
DNA sequencers are eventually expected to be able to read each of the 3 billion chemical subunits strung together to form the 50,000 to 100,000 genes that make a person what he or she is.
And there is enormous interest in reading the whole genetic code. Some scientists recently proposed that the federal government undertake an all-out effort to translate the code. Such a project, they estimate, would take 5 to 10 years and cost $2 billion to $4 billion.
The rewards gained from reading the entire code are expected to be great. Researchers hope that the sequencer will someday be able to pinpoint the errant subunits that cause many of modern man`s ills.
Some researchers believe it will even be possible to produce genetic fingerprints of fetuses in the womb. Such a gene map would have enormous implications on a youngster`s lifestyle, diet, career choice–and possibly even the selection of a spouse.
”It would be an incredible accomplishment, the likes of which would dwarf anything else we`ve done in understanding the genetic hardware, the fundamental biology of the human organism,” said Dr. Leroy Hood, whose Cal Tech team developed the DNA sequencer as well as earlier machines that can make artificial genes and proteins.
But because genetic fingerprints would reveal extremely basic and intimate information about people, there is growing concern about possible misuse of them, especially by potential employers and insurance companies. Others worry about a big increase in abortions as parents reject fetuses they deem to be imperfect.
Pasteur`s identification of germs as the cause of infections eventually led to improved hygiene and sanitation, public health measures and the development of antibiotics and vaccines. Infectious diseases, which throughout history had been the major killers of people, were tamed.
They were replaced as the principal health threats to humans by heart disease, cancer, high blood pressure, diabetes and other chronic ailments that we know are closely related to lifestyle. And what might be called the gene theory of disease postulates that almost all of these common ailments, including mental and character disorders, are linked to defective genes.
Scientists apply the term ”ecogenetics” to the study of the relationship between genes and enviromental influences. Like the germ theory before it, the gene theory seems certain to have enormous ramifications.
”Genetic screening is going to be accurate, not like family histories of genetic disorders,” said Daphne Kamely, a U.S. Environmental Protection Agency geneticist. ”This is really going to give you a personal map of what you have in you. It`s just a matter of time.”
People with known genetic predispositions for heart disease or cancer, for example, would be able to improve their chances of remaining healthy by avoiding environmental exposures and other risk factors believed to trigger those diseases. People without such predispositions could lead freer lives.
”Currently, we tell the whole population not to eat butter, eggs, high fat foods and salt,” said Dr. Arnow Motulsky, director of the University of Washington`s Center for Inherited Diseases.
”With genetic screening we will hopefully be able to identify people who are at high risk for various diseases. There may be a large group in the population who could eat whatever they want.”
This new approach to illness has been made possible by progress in understanding the genetic code. Each human cell contains a complete library of genetic instructions, which dictate the development of a person from a single fertilized egg to a mature adult and which regulate all of his biochemical functions throughout life.
The code is both simple and complex. It consists of four chemicals, called bases: adenine, thymine, guanine and cytosine. Like the letters in a biological language, they are repeated millions of times to spell out the messages encoded in DNA. Adenine always combines with thymine, and guanine always pairs up with cytosine.
The genetic material in all living things contains these same four bases. It is the sequences in which they are arranged that determines whether they will build a bacterium or an elephant.
Combinations of bases form the rungs of the ladder that twists in long strands to create the double helixes that make up genes. Each gene contains many thousands of these bases.
Genes, in turn, form the 46 chromosomes that are found in human cells. The chromosomes in each cell contain about 3 billion chemical bases. Packed into the chromosomes is enough information to fill 13 sets of encyclopedias.
The Cal Tech DNA sequencer reads each individual base. Fluorescent dyes are ingeniously attached to each base to color code them and then a laser system illuminates the dyes and identifies the specific colors.
”What this machine does basically is to decode the letters in the human genetic library,” said Hood. ”Combined with other technologies, we`ll be able to decipher these letters and make out the words and understand what the rules are by which humans are constructed and by which genetic diseases are caused.”
Except for identical twins, no two people have the same genetic makeup. Genetic variations account for differences in size, color of hair and skin, physical features and all the other evident distinctions in the human species. Scientists believe that differences in genes may also make some people more susceptible to certain diseases when they encounter external triggers, such as chemicals in the workplace, cigarette smoke, fatty foods, radiation, germs and other environmental exposures.
Most of the triggers are relatively new to humans. Today`s typically rich, high fat diet became common only after the turn of the century. And there are more than 55,000 chemicals now in use, most of which were introduced after World War II.
Scientists have long known that defective genes cause many classical genetic diseases, such as Down`s syndrome, Tay Sachs Disease, Cystic fibrosis and Huntington`s chorea. Genes have been linked to about 3,000 of these inherited disorders.
But it appears that many of the common diseases that people used to think they got as a result of chance or bad luck are also programmed into their genetic codes.
And this approach to illness begins to answer the age old question, ”Why me?” Only one of five heavy cigarette smokers, for example, develops lung cancer.
In the case of cancer, recent evidence indicates that people carry oncogenes, which normally are turned off after fetal development. They may, however, be turned on again to produce cancer when they are subjected to a
”second hit” from some environmental insult, such as a chemical.
Evidence that a single defective gene may predispose people to the most common form of heart disease was announced last month by scientists at the University of California`s Lawrence Berkeley Laboratory.
The gene normally performs a vital role in cholesterol metabolism, but in about 15 percent of the population the gene is defective, producing an errant form of cholesterol. Only in adulthood, after many years of abnormal functioning in conjunction with a high fat diet, does the damage accumulate to cause fat-clogged arteries, the researchers believe.
”Discovery of a genetic component in heart disease should not encourage anyone to take a fatalistic attitude or to de-emphasize the importance of exercise, diet, drugs and changes in lifestyle,” said Dr. Ronald Krauss, who headed the Berkeley team.
”The proposed gene is just one of many risk factors, and just because you carry it does not mean that you are necessarily stuck with heart disease in your future. On the contrary, if people at risk can be identified early enough, we have every reason to believe that we will be able to reduce their risk by diet or drug treatment.”
But some other scientists fear the field is moving too fast. The growing ability to diagnose flawed genes will, in the foreseeable future, far outstrip our ability to do anything about them, especially the ones that cause serious congenital defects. As a result, these scientists fear, there will be an increased push to abort fetuses not considered to be genetically perfect.
”We`re going to have the ability to predict before we have the ability to do any kind of conventional treatment,” said Dr. Neil A. Holtzman, who is on leave from Johns Hopkins University to work with the U.S. Congress Office of Technology Assessment.
”The danger is that this new technology may be misused,” he said.
”. . . You blame the genes. There will be issues of discrimination and an increasing tendency to use prenatal genetic screening and abortion even for late onset diseases.”
Genetic screening in the workplace, already tried on a small scale, may become more widespread as a means of protecting susceptible workers from exposures to certain triggers. But there are fears that workplace screening could be used to discriminate against job applicants.
”It is something people are resisting because they think it will label them in one way or another,” said EPA`s Kamely. ”They are saying that `God forbid that a decision on whether I`m going to be hired or not will depend on what`s in my genes.` ”
The ability to closely read a person`s genetic code could necessitate a re-examination of the notion of the right to privacy.
”We may ultimately decide that the detailed information about an individual`s genome (genetic code) belongs squarely in the sphere of the right to privacy,” said Dr. LeRoy Walter, director of the Center for Bioethics at Georgetown University`s Kennedy Institute of Ethics.
”Perhaps no one else should have access to that information unless an individual chooses to disclose it for therapeutic purposes.”
There will be pressures from employers to know if workers have genetic susceptibilities to certain diseases, he said. Health and life insurance companies may insist on genetic screening–even of fetuses–before they provide coverage, just as they now require physical exams.
People may also want to know the genetic makeup of potential spouses to avoid the risk of passing on genetic diseases or susceptibilities to their offspring.
The growing ability to identify flawed genes or there markers is a result of the stunning new field of genetic engineering, which began in 1973. Then, for the first time, researchers transferred working genetic material from one species into another.
Since that first step, scientists have discovered enzymes that allow them to cut the genetic code into gene-sized fragments and paste different ones together. Dismantling the code permits them to develop probes to look for individual genes, learn what they do and identify those that cause disease.
More than 500 genes have been completely sequenced, their function has been learned, and their exact positions on chromosomes have been mapped. The function of several thousand more genes has been figured out, but their positions on chromosomes have yet to be mapped.
Ninety percent of the human genetic code has been cut into fragments, said Larry Deaven, chief of the gene library project at the Los Alamos National Laboratory in New Mexico. The gene fragments are being sent to investigators all over the country to figure out their sequences, what they do and where they are located on chromosomes, Deaven explained.
One of the most promising approaches is being conducted at the National Cancer Institute under the direction of Dr. Harry Gelboin. The institute is investigating the genetic basis of a key family of enzymes called cytochromes P-450, which exist in almost every cell and act as the body`s first line of defense against the sea of chemicals people are exposed to.
The P-450s break down such workplace chemicals as benzopyrene, the No. 1 environmental chemical carcinogen, benzene and napthalene. When the enzymes work properly, they convert potentially dangerous chemicals into harmless ones in a series of as many as 40 metabolic steps.
When one of those steps is abnormal, because of a defective gene, the chemical could be turned into a cancer causing agent. The institute`s job is to identify those errant enzymes so that people who have them can be warned about working in environments where they may do more harm than good, said Gelboin.
The P-450s also metabolize drugs. Variations in these enzymes is the reason why the same dose of drug given to two people of the same weight will be metabolized at vastly different rates, he said. Gene variations also explain why some people experience serious, potentially deadly drug reactions. Similar tests are being developed for many other faulty gene products that enhance a persons risk of developing disease.
”We probably will be able to develop a genetic fingerprint of everybody in 10 to 15 years,” said Gelboin. ”The technology is already here. It`s a matter of being souped up.
”With a genetic fingerprint we may be able to determine the dose of a drug a person gets, what kinds of drugs he should or shouldn`t get, where he should or shouldn`t work, the kinds of foods he should eat, where he should live and the kind of lifestyle that would be best for him.”
