The potential use of genetic engineering, the alteration of the genetic material (i.e. DNA) in living organisms, for therapeutic purposes, or “gene therapy”, holds the promise of curing many diseases. The potential use of gene therapy as a preventative treatment for genetic diseases, however, has been controversial, primarily because such preventative measures may involve manipulating the embryo. The beginning of life is an event so universally cherished that any interventions made in this somewhat ambiguous period that marks the beginning of existence, even to prevent disease, is simply too sacrilegious to consider. Yet, at the rate that science is progressing, such interventions may become reality in the near future. Our ability to alter DNA to cure diseases has raised an important question for physicians and scientists alike: should a line be drawn between utilizing genetic engineering for curing and preventing disease?

The Future According to Andrew Niccol and Lee M. Silver

Andrew Niccol’s 1997 film, Gattaca, depicts a society in the not-too-distant future where prenatal genetic screening designed to eradicate disease and undesirable personality traits has become such a routine service that the “natural” way of conception occurs in the hands of a geneticist. The protagonist, Vincent, who was brought into the world through conventional conception, belongs to an underclass (the Invalids) that was no longer determined by social status or skin colour, but by the genes in one’s cells. Vincent dreams of going to space, but prestigious careers like astronauts are reserved for the genetically elite. In the same year, Princeton University professor Lee M. Silver makes a similar prediction of a futuristic society with a genetically-determined caste system in his book, Remaking Eden. Humans conceived by conventional birth, or “Naturals”, receive only limited education and have the least wealth and power while humans who have received prenatal genetic enhancement, the “GenRich” have access to the majority of resources and hold all decision-making roles in the community. Social segregation becomes so prevalent that by the third millennium, the Natural and GenRich classes become so genetically different that they are no longer able to reproduce between classes and humans differentiate into several separate species.

Both scenarios highlight some of the fears we have about what could happen if reproductive and genetic technology combined becomes available for the purpose of enhancing the human race. Interestingly, these two scenarios were conceived in the same year that Dolly the sheep, the first mammal to be successfully cloned from an adult somatic cell, was born. This landmark achievement in cloning could very well make these science fiction stories reality. Now, a mere decade later, the Human Genome Project, an endeavor to identify all the genes in human DNA (previously thought impossible), has already been completed for four years. Empowered with knowledge and technology the ability for expecting parents to control their child’s genetic predispositions to disease may become possible sooner than we are ready for it.

The Current State of Reproductive and Genetic Engineering Technology

Currently, the utilization of genetic engineering to treat disease is still in an experimental phase. The diseases that would likely benefit first from gene therapy is a group of genetic diseases that occur due to defects of a single gene, or monogenic diseases. Some examples include cystic fibrosis, haemophilia, Huntington’s disease, lysosomal storage disorders, and achondroplasia, the most common cause of dwarfism. The origin of monogenic diseases can be traced to a single defective gene. Since the disease arises from a defective or non-functional gene, the correct functional version of the gene can theoretically be delivered into the cells by non-pathogenic replication-deficient viruses to restore normal function. However, since the correct version of the gene gets integrated randomly with the genetic material already in the patient’s cells, there is a risk of disrupting the function of otherwise functional genes or activating genes that are usually inactive which may lead to cancer. In the few clinical trials have been done, sustained clinical improvement has not been consistently achieved. Part of the reason for the short-lived effectiveness is because the patient’s body mounts an immune response against the foreign viruses which are used to deliver the correct version of the gene into the cell. In addition to limiting the sustained effectiveness of therapy, host immune response also limits the safety of gene therapy. On September 17, 1999, 18-year-old Jesse Gelsinger, who suffered from a monogenic liver disease called ornithine transcarbamylase deficiency, became the first patient to die as a direct result of gene therapy. The response that his immune system mounted against the viruses that delivered the therapeutic genes was so large that it caused multiple organ failure. To date, much work is still being done in animals to address these issues and until these concerns are assuaged, it is unlikely that gene therapy, even for monogenic diseases, will be widely used.

Having said that, it is not at all early to start thinking about what exactly we are trying to achieve with gene therapy. Couples today have more control over their reproductive lives than ever before. Prenatal diagnosis of monogenic disorders by DNA analysis using either samples of the amniotic fluid or placenta has been available to expecting parents for several decades now. Since raising a child with a monogenic disease may require changes in lifestyle and present challenges that differ from raising a healthy child, this technology allows expecting parents to become more prepared for the birth of a child, or to decide to terminate the pregnancy should a positive diagnosis is made. In the last decade, pre-implantation genetic diagnosis became available. Now, embryos generated by in vitro fertilization can be subjected to the same tests that would be done in a prenatal diagnostic procedure, and only the ones that are tested to be disease-free are subsequently implanted and allowed to develop to full term. Proponents of the preimplantation genetic diagnosis suggest that this new technology reduces the prospective parents’ anxiety by removing the need to face the difficult decision of terminating a pregnancy. However, for those who believe that a pre-implanted embryo deserves as much respect as an implanted one, the distinction between the two genetic diagnostic technologies is of little consequence, since both procedures result in the termination of life. The power of combining gene therapy with reproductive technologies lies in its ability to change this.

Assuming that gene therapy will one day be refined enough to use on humans, it is conceivable that embryos testing positive for a disease gene during pre-implantation genetic diagnosis may no longer have to be discarded even if the expecting parents desire a healthy child. The therapeutic gene could be delivered into the embryonic cell before placement into the uterus for implantation. This hypothetical method of gene therapy is different from genetic screening procedures in that the decision to terminate life, no matter how it is defined, is truly eliminated. Another attractive benefit is that treatment of genetic diseases at the root of the problem (the DNA) will limit the transfer of disease from generation to generation. Would this form of therapy be as accepted as much as gene therapy performed on newborns or adults? From a purely therapeutic point of view, it should. In utero surgeries performed before birth are currently not only socially accepted but are regarded as life-saving achievements performed only by the best specialists. For example, in January 2006, Grace Van Derwerken became the world’s first fetus to be successfully implanted with a cardiac device to treat a congenital heart defect at Children’s Hospital Boston. What if instead of reversing an inborn genetic disease, the same strategy was used to confer genetic resistance to potentially acquired diseases such as AIDS? Indeed, there are versions of genes that occur naturally in some subpopulations of Eastern Europeans that confer higher resistance to infection by the HIV virus (the virus that causes AIDS), which could conceivably be harnessed for preventative genetic treatment. If we can accept the eradication of disease by vaccination in the 20th century, what is it about bringing gene therapy to the preimplant embryo that causes such great consternation?

Little and Not-so-little People

The fear of discrimination lies at the heart of opposition to genetic engineering. We would all like to believe that all life should be valued, but no one condemns the expecting parents who desire a healthy child. After all, parents will always want the best for their children. Yet, some consider it discrimination to make the assumption that a life without disease is “best”. In two documentaries, Little People and Big Enough, filmmaker Jan Krawitz interviews individuals afflicted with dwarfism who were convinced that dwarfism does not require a cure. They argue that people with dwarfism can live long, fulfilling lives. Dwarfism is a condition of short stature that in itself is not a disease, but the most common cause of dwarfism, achondroplasia, can indeed be defined as a disease. According to the Merriam-Webster dictionary, a disease is a condition of the living animal or plant body or one of its parts that impairs normal functioning and is typically manifested by distinguishing signs and symptoms. The abnormal short stature of a person with achondroplasia impairs normal growth and respiratory function and results in complications such as bone deformity, nerve compression, and chronic pain. With an imminent potential genetic cure for achondroplasia (a monogenic disease), it may be shocking for physicians and incomprehensible to scientists why people would reject a solution to these severe and often disabling complications. Note however, that these people who seem to be reluctant to be cured are making an assumption that to some extent exist at a societal level, that the worth of a sick person is generally considered to be less than that of a healthy one. Such a discriminatory world view can only be overcome by recognizing that living with disease and living a purposeful life are not mutually exclusive.

If we look at some of the attributes that make a person valuable – their character, their achievements, their contributions to society, we can see that assigning less value to the lives of sick individuals is clearly unwarranted. Consider the numerous individuals in the 20th century who suffered from a disease but still made their mark on humanity [1]: Abraham Lincoln (Marfan’s syndrome), Emily Dickinson (manic depression), Vincent van Gogh (epilepsy), Albert Einstein (dyslexia), John F. Kennedy (Addison’s disease), Rita Hayworth (Alzheimer’s disease), Ray Charles (primary glaucoma), Stephen Hawking (amyotrophic lateral sclerosis), and Jackie Joyner-Kersee (asthma). I am not trying to reason that disease made these people who they are and that we should therefore discontinue attempts to cure disease (an argument used by Silver to discredit arguments against genetic engineering). The point I’m trying to make is they were able to achieve despite their disease. These individuals are testament to the faulty logic that sick people are less able to contribute to society, to achieve, or to inspire.

In a society so focused on finding cures, we sometimes forget to the primary purpose of finding a cure is to prolong and improve the patient’s quality of life. The promise of pre- and post-natal gene therapy can achieve this goal, and therefore should be pursued. One must realize, however, that although medicine strives to prolong life, it cannot add value to a person’s life. Most Canadians know of Terry Fox. Medicine was unable to save him from cancer or to prolong his life much longer than his short 23 years, yet he continues to be an inspiration to people sick and healthy alike and his legacy to cancer research lives on. Perhaps less well-known to the North American audience is the story of Chi Mo, a young man with haemophilia who contracted AIDS through a contaminated blood transfusion. Before succumbing to AIDS at the age of 23, he actively campaigned for AIDS awareness in Hong Kong to discourage discrimination against AIDS patients. He leaves his legacy with an inspiring and personal autobiography. Consider my upcoming 23rd birthday, my impact on society as a healthy person pales in comparison. Another thing is, although cures may alleviate the physical and emotional suffering associated with diseases, it does not automatically follow that a disease-free life is free of suffering. On the same lines, if the quality of life is to be gauged by happiness, then one cannot assume that a good quality of life occurs only in the absence of disease, for there are sick people who are happy and healthy people who are not. In the end, medicine may make life easier but not more meaningful.

A Catastrophe of Success?

What then, is the goal of medicine? To a certain extent, medicine is not so much about curing than about helping people achieve their ideal notion of being human. The undesirable shape of one’s nose does not impair normal physiological function and is therefore not a disease, but yet physicians and surgeons trained in medicine provide their services to fix such “problems” through cosmetic surgery. As the field of gene therapy develops, it is inevitable that a new kind of cosmetic field will also rise. With current in vitro fertilization techniques, it is already technologically possible for expecting parents to choose the sex of their child before birth. Conceivably, the marriage of genetic and reproductive technology may eventually enable parents to specify physical traits such as hair colour, eye colour, and build for their child. As we gain the ability to control more and more of what was previously left to chance, whether maximizing human potential through science puts humanity itself at risk of becoming lost in the a pursuit of superficial ideals becomes an increasingly relevant question.

Perhaps the greatest catastrophe of the success of gene therapy will be the unrealistic expectation of perfection. We fear that with technology that better enables us to reach perfection, the societal stigma of disease today will slowly evolve into a stigma of imperfection, health-related or otherwise. This is a reasonable fear, unless we devote ourselves to nurturing the idea that every life has value and therefore deserves respect. Instead of valuing perfection, we need to value an individual’s ability to overcome imperfection and adversity because even if gene therapy ends up eradicating diseases and their sequelae, or if genetic enhancement makes us look and perform as we would like to, we will not be perfect human beings for a simple reason that once we achieve perfection as we know it, we will already have replaced what we hold to be perfect by something else we have not yet attained.

As of 2007, which marks the ten year anniversary of Gattaca, the movie’s tagline still holds true: there is no gene for the human spirit. As a scientist, I am open to the possibility that this will one day be proven wrong. Yet, the human experience does not solely rely on the genes in our cells. The pursuit of ideals, which by definition are unreachable but are pursued nonetheless, the triumph of human determination against all odds, are human qualities that exemplify why our existence cannot be understood by scientific reasoning alone, if at all. It is this struggle to achieve what is never quite attainable that we call life, and it is because of this struggle that life is so deserving of respect.

1. These are the individuals featured in a video montage available on the DVD of Andrew Niccol’s Gattaca.

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