Germ Line Gene Therapy

Germ Line Gene Therapy Whether it is referred to by its scientific term syngamy or by the general term conception, the moment a sperm cell unites with an egg cell stirs, both in the scientist and the layperson, much awe and reverence. It is the point at which a new and unique genome is created. To some it is the instant a new person comes into existence. Such a union has been repeated for billions of years since its advent in the first, simple organisms. It is a means by which evolution can exert its influence. When the genetic material of two individuals combine in sexual reproduction, any variations between the two inherited sets of genes may result in offspring that are more or less suited to its environment.

Human beings have come to a point in this process where we can now, to an extent, shape the environment to suit our needs. The evolution of intelligence in our specie is the characteristic that has had the most profound impact on our planet and on us. This intelligence, among other things, allows us to understand and combat some genetic diseases. Inventions such as spectacles to correct our vision or drugs that fight heart disease and cancer have extended and improved the lives of individuals who, in a more Darwinian world, would have otherwise been eliminated by natural selection. Cheating this process, however, has allowed a multitude of genetic diseases such as Tay Sachs and hemophilia to propagate in our gene pool. But researchers are taking the field of medicine to a new frontier that promises to eliminate genetic diseases.

New technology is being developed that will allow scientists to alter or replace defective genes in germ-line cells (egg and sperm cells). In a literal sense it will allow us to control the evolution of our specie as these alterations may be passed on from generation to generation. The implications are profound for the individual and for society. Above it all the specter of eugenics, the process of selected breeding to improve the human race, hovers and reminds us of the danger that such technology may create. But careful public deliberation should allay fears and allow us to develop an ethical framework that will guide society and the scientific community in any decision making process.

It is in this regard that we should allow research in this field to continue as it promises more real benefits than imagined dangers. For the past two decades, gene therapy promised to cure genetic disorders such as cystic fibrosis, sickle-cell anemia, and even cancer. Despite the progress of this technology, few have benefited. The problem is getting new genes into enough cells, and keeping them there long enough to do any good. Germ-line engineering promises to circumvent these difficulties. Through this technique, only one cell, a fertilized human egg (a germ cell), needs to be altered.

After subsequent cell divisions and then implantation into the uterus, the cells that divide and grow will each have the alteration. Sharon Begley describes one scenario in her article, Designer Babies (Newsweek, November 9, 1998). At an in vitro-fertilization clinic a couple has an artificial human chromosome inserted into their fertilized egg. One of the genes on this chromosome will carry the instruction ordering cells to commit suicide. The embryo will be implanted into the mother’s uterus and eventually a baby boy will be born.

Some fifty years into the life of the genetically altered man he, like the men in his family before him will develop prostate cancer. However, Begley continues, The cell suicide gene will make his prostate cells self-destruct. The man, unlike his ancestors, will not die of the cancer. And since the gene that the doctors gave him copied into every cell of his body, including his sperm, his sons will beat prostate cancer too. The situation described is still far from being realized.

But technology is moving along and its implications are already fully realized. Begley’s article reports on a recent symposium held at the University of California, Los Angeles. An advisory panel consisting of distinguished scientists set out to summarize the advances in the field of germ-line therapy and to discuss its implications. It was hoped that this public forum would address concerns so that progress of the technology would not be hindered by knee-jerk legislation. Currently, according to the article, the National Institutes of Health refuses to even consider funding proposals for germ-line research. Biophysicist Gregory Stock of UCLA sums up the most profound implication of this research. Life would enter a new phase, one in which we seize control of our own evolution.

Reports of recent research presented at the symposium show that scientists are working on ways to circumvent any inherent ethical issues. Among these is a method to remove the altered or new gene when it is present in egg or sperm cells using biological scissors, hence, preventing any alteration from being passed on to subsequent generations. So it seems that someday only the benefits, not the dangers, of this technology may realized. Certainly Begley gives that impression. Only briefly does she touch on some of the negative implications of germ-line therapy. For the article, a more in depth examination of issues such as eugenics, informed consent for the altered child, or the creation of a social stratum of genetic haves and have nots might have included quotes from persons opposed to germ-line therapy. The article merely reflects and conveys the optimistic view held by the pro-research panel. While Begley seems to gloss over the ethical morass that germ-line therapy might create, Paul Gray devotes his article, Cursed by Eugenics to discussing one of the more significant dangers of this technology (Time, January 11, 1999).

Although researchers may find ways to keep germ-line alterations form being passed on to future generations, eugenics would be an ever-present concern to society. Gray tells a cautionary tale by recalling a time when the theory of eugenics promised to eliminate inherited traits that weakened a society. At the turn of the century, traits such as feeblemindedness, epilepsy, criminality, insanity, alcoholism, pauperism were believed to be inherited. Therefore, with controlled and even legislated breeding such characteristics could conceivably be eliminated. According to the article, many U. S.

states enacted laws requiring the sterilization of those held in custody who were deemed to suffer from hereditary defects. Gray also compares eugenicists of the past with molecular biologists of today. He describes eugenicists as usually well-meaning and progressive types who wished to help people. This implies that the same motivations drove eugenicists to embrace their beliefs, perhaps, drive today’s scientist to develop techniques in gene therapy. The infectious optimism of the science community can be found spreading throughout society today, he suggests.

He continues that the fervor created by the promises of an improved population by way of science led to some of the worst atrocities our world has known. He writes, nowhere, of course, were eugenic theories more enthusiastically codified into binding state doctrine than in Nazi Germany. The suggestion that gene therapy may potentially lead to horrors comparable to the holocaust are discouraging indeed. Though not likely to occur, such viewpoints can be appreciated for the guidance they may one day provide. Gray closes, [The eugenicists] were wrong, with unintended consequences for millions of people. But the legacy of the eugenicists may be instructive.

The next time you hear someone promoting the scientific improvement of the human race, think of them. Within the past century, the United States population has seen its life span go from an average age of forty-seven years to seventy-six years (Time, January 11, 1999). This dramatic change in life expectancy, however, has not been a result of medical advances. Rather, changes in public health policy can be credited for this remarkable difference. But as we enter the next century, medicine promises to be the significant force influencing the health of the population.

It is expected that advances in the biotechnology field will soon find cures for diseases such as cancer, muscular dystrophy, or Huntington’s disease. When we begin to understand the genetic mechanisms of these diseases we will then be able to manipulate them. Such manipulation will most likely come in the form of gene therapy. Thus far, conventional techniques of gene therapy have not been beneficial. As a result, researchers have looked for new tools in the fight against genetic diseases.

The most promising of these is germ-line therapy since it can, theoretically, circumvent the problems inherent in conventional gene therapy methods. Many questions have come to light in regards to the ethics of such technology. Will society ever encounter issues like eugenics or the manipulation of evolution because of germ-line therapy? Such questions may not be answered for years. What is certain and what is real is that the benefits of such research hold the promise of improved health for many people. Scientists and society have made many mistakes in the past based on faulty scientific theories.

With these mistakes in mind and keeping fresh the memory of the suffering caused by such ideas, science should forge ahead. Through continuously stimulated public debate and thorough, careful research, germ-line therapy can progress at a rate that would allow our children to be the first to benefit from this technology. Medicine and Health Care.