Departments
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Week of 24 October 1997 |
Vol. I, No. 9 |
Feature Article
Should evolution be guided by genetic control?
University Lecture wrestles with ethics of tomorrow's biomedicine
by Jim Graves
When ideas for the vast Human Genome Project began germinating in the late 1980s, few of the early planners anticipated creating the new field of genomics, in which thousands of people now work. Today, moreover, there is wide agreement that the Human Genome Project to decipher the human genetic code "is already a tremendous scientific success. By and large, it is ahead of schedule and under budget."
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Professor Charles Cantor, a pioneering researcher in the new field of genomics, delivers the University Lecture against a backdrop of DNA sequences. Photo: Vernon Doucette |
The Human Genome Project aims to isolate DNA pieces of all the estimated 100,000 human genes and to determine the DNA sequence of the three billion base pairs that represents a complete copy of human DNA. Likewise, model organisms are being studied to provide comparative data. As "the first large, focused project in the history of biology," the undertaking represents, he said, "a true paradigm shift for a significant sector of biological science and for commercial activities derived from this science."
Successes to date of the project include the "completion of more than seven genomes of unicellular organisms," Cantor said. The work on these simple organisms has proceeded much faster than work on humans, mice, or the fruit fly. Yet private firms have sprung up and have "accelerated the search for genes important in selected human diseases," while others have "focused on large-scale sequencing of expressed genes [genes that are active in the sense that their RNA and perhaps their proteins have been created], usually by making DNA copies of pieces of cellular RNAs called complementary DNAs [cDNAs] and sequencing these RNA fragments."
By a conservative estimate, eight such firms had come into existence by April of this year, with a total worth of around $2.5 billion, and their genomic activities are now greater than those of government-funded projects. By concentrating on cDNAs, they have been able to find fragments of most human genes. "These, fragments," Cantor said, "can now be extended to full-length cDNAs [DNA copies that correspond to the information in entire genes], and thus the genes they represent will be known and available for study without the need for full genome sequencing. One can argue, and many do, that the cream of the genome project has been skimmed by these private-sector interests."
In any case, technical difficulties preclude full sequencing of a representative of every human chromosome, as was originally promised. The more attainable goal now, Cantor said, is to sequence all the genes and the regions in which they reside. This will require continued development of innovative technology.
The use of enhanced methods now being developed to enlarge the scale on which experiments can be performed, Cantor said, will be useful in locating genes associated with human diseases. But he cautioned that "DNA sequence information alone can rarely provide definitive information about the function of particular genes . . . " since function involves "the interplay of many gene products, many proteins at once." Yet such information does have the potential to revolutionize medicine, though a time lag of 10 to 20 years is likely between discovery and medical advances.
"The first practical consequences that will emerge," he said, "are improved abilities to predict disease risk." And, he warned, "there will be those, like health-care insurers or potential employers, who will seek access to the results of such genetic tests to screen out individuals" who are at risk. There is, he said, near unanimity that like other medical records, genetic records should be kept private.
Rapid strides in diagnostics will come about, he said. And by monitoring human DNA variability and correlating it with patients' therapeutic responsiveness, new methods for treating or curing diseases will emerge. In many cases, people who have been determined to be genetically predisposed to a disease will be able to takes preventive measures by lifestyle changes, such as protecting themselves from prolonged exposure to sunlight or by changes in diet. Whether they actually do so, however, is another question. As in the case of those who persist in smoking or other dangerous activities, "Most people are willing gamblers; indeed there may even be genes that predispose towards such behaviors," Cantor said.
Eventually, knowledge of specific disease gene alleles (genes belonging to groups of genes occurring alternatively at given places) will lead to more effective treatment of these diseases. "More drugs, more effective drugs, and cheaper drugs should become broadly available," he said.
Cantor closed by posing ethical questions growing out of the Human Genome Project. Knowledge gleaned from the project will, for example, lengthen life spans. "However, the downside is that with a constant birthrate, the earth's population will increase proportionally to the increase in life span," Cantor said. With people living longer, medical costs will rise. The alternative seems to be mandated euthanasia on a mass scale à la Aldous Huxley's Brave New World, "but by current standards, voluntary termination is totally unacceptable."
Gene therapy will cure disease by replacing deleterious alleles with normal ones, a procedure posing no ethical dilemmas. But an ethical question is raised by a technique known as germ line gene therapy, he said, where "the goal is to change all the cells of an individual in a heritable way. Today, germ line gene therapy is already practiced in such examples as sex selection by selective abortion. Disease alleles can be eliminated in precisely the same way. It is a relatively safe and cost-effective procedure. Whether society should encourage it must inevitably be decided by issues of both quality of life and morality. Thus, preventing the birth of an individual whose life would be seriously substandard seems relatively easy to defend, while preventing a birth just on sex alone, or other frivolous characteristics, seems mor-ally reprehensible."
Genetic research will produce the knowledge of how to improve the genetic makeup of the human species. The difficult question Cantor asked is, "Should we do this? I think the question can be answered only from an evolutionary perspective. Evolution operates at the level of the species. It ensures that the most fit species survive and prosper. . . . The bottom line is clear enough; genetic variability . . . must be preserved. Mankind is already master of its evolution by environmental control. Why not take a much more active role and guide that evolution by genetic control? Is this not the next step in evolution when a species finally gains this ability? I find this a terribly difficult question, and I am relieved by the realization that it will probably not have to be answered in my lifetime."