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LeRoy Walters provided a valuable perspective on some of the lessons learned by scientists and ethicists over the 18 years since the first human gene therapy protocol was approved. He also offered his predictions for future gene-therapy interventions and discussed some associated ethical dilemmas that society may be facing.
Walters began his talk with two case studies. The first was about David, known as "the boy in the bubble." He was born in 1971 with X-linked severe combined immune deficiency and died 12 years later after receiving a bone marrow transplant that, unknown to doctors, carried a silent Epstein-Barr virus.
In contrast to David's story, Walters continued, is the story of Ashanti, who was born in 1986 with an autosomal recessive form of severe combined immune deficiency. In Ashanti's early years, every environmental microbe attacked her body and made her sick. She was treated with a synthetic enzyme called PEG-ADA, which gradually decreased in efficacy, and in 1990 she became the first patient to receive gene therapy in an approved protocol. She is now almost 13 years old and living a normal life.
In reviewing the history of gene therapy in the United States, Walters referred to a document prepared by an interdisciplinary group in 1984 and 1985. Called "The Points to Consider," it contained 110 questions that investigators were asked to answer as they thought about performing gene therapy on human patients. The questions covered such topics as gene therapy's potential benefits and harms, fairness in selection of recipients, procedures to be followed, recipients' privacy and confidentiality, and possible alternative therapies. The same questions could constitute a checklist for gene therapy today, Walters said.
The review process in the early days was transparent and public, a fact that was important to gene therapy's acceptance. Policymakers knew exactly what was happening, and any member of the public could attend a meeting, see the investigators, hear the questions, and have access to a public list of approved gene therapy protocols.
Walters stated that as of February 1998, 200 therapeutic protocols had been formally reviewed: 23 dealing with HIV infection or AIDS; 33 with single-gene diseases, especially cystic fibrosis; 138 with cancer; and 6 with other diseases. Reviewing what has been learned from the past 18years, he listed the following points:
Looking to the future, Walters said he thinks we will see prenatal interventions to prevent severe and irreversible damage to fetuses and gene transfer to prevent or treat neurological disease. In studies affecting the brain, the question of what is enhancement and what is cure, treatment, or prevention of disease will arise in an acute form, he said. For example, is it remediation or enhancement to intervene so that a child would have an IQ of 100 instead of 60 or 70?
Walters predicted that, in the next 18years, proposals will emerge for germline genetic intervention, which will require a great deal of preliminary technical work. Instead of the current technologies of adding genes, something analogous to the "search and replace" function on a word processor will be needed to find the malfunctioning gene, splice it out, and replace it with the properly functioning gene.
He pointed out that there are some good moral arguments in favor of germline genetic intervention, whose goal is to prevent or alleviate disease or disability. Such intervention is more efficient than repeating gene therapy generation after generation, and even in utero gene therapy is too late for some diseases. The one case that could justify nuclear transfer in the early embryonic stage, Walters thought, is that in which a woman is likely to pass on a mitochondrial disease to her offspring. In such a situation, he said, after in vitro fertilization it would be justified at perhaps the four-cell stage to remove all the cells' nuclei and fuse them with enucleated egg cells from a donor. Because mitochondria are in the cytoplasm and would be derived from the donor, the resulting embryos would be free from mitochondrial disease. This type of case would involve simultaneous germline intervention and cloning in the technical sense.
Walters ended with a warning against repeating mistakes made in the time of the eugenics movement and the Third Reich. "We can applaud the war on disease that genetic research is waging. It will be a great day when a child is definitively cured of cystic fibrosis or when a particular family line is liberated from the burden of fragileX syndrome. But we will be humane warriors only if, in the midst of the battle, we also show respect for those who courageously cope with disability and for those who cannot yet be cured."
[LeRoy Walters, email@example.com]
The electronic form of the newsletter may be cited in the following style:
Human Genome Program, U.S. Department of Energy, Human Genome News (v10n1-2).
The Human Genome Project (HGP) was an international 13-year effort, 1990 to 2003. Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome. See Timeline for more HGP history.