By Robert Hazen, George Mason University
Human ailments are by far the central focus of today’s genetic engineering of animals. Once a genetic disease has been diagnosed—by gene typing—we’re faced with a question of how, and whether, the human genome should be altered to correct that disease. Genetic engineering of humans to cure inherited disease is what’s called gene therapy, and there’s much research going on in this area today.
Not that Straightforward
In principle, gene therapy accomplishes the same kind of genetic changes as the genetic engineering of microbes or plants. That is, one can add a gene to a genome, try to turn off or delete a gene, or one can try to correct the spelling of a gene. In practice, however, modifying human genes, even for therapeutic purposes, is a daunting challenge. It combines scientific hurdles, and moral complexities as well, because altering our genetic state is something that raises really serious ethical questions.
Animals undergo an extremely complex process of cell differentiation. We start with a single cell, the fertilized egg; but very soon, in the process of development, as the cell divides over and over again, we start seeing specialized cells: blood cells, brain cells, nerve cells, and so forth.
We really don’t know how to clone a human being from one of these single, differentiated cells; as a consequence, it’s difficult to see how we can apply a gene therapy that will treat the entire body and correct all the cells within a body. Nonetheless, this is a very serious and important challenge, as in it lies the promise of improved treatment, or even cures, for diseases that are now incurable.
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The ‘Bubble Babies’
The bright potential of gene therapy was epitomized by the story of Ashanthi DeSilva, who was born in 1986 with a devastating genetic disease, an illness called, combined immunodeficiency. This results from a defect in one specific gene, a critical enzyme called adenosine deaminase, or ADA. The lack of this ADA enzyme prevented her immune system from responding to bacterial invaders.
Children suffering from combined immunodeficiency disease are often confined to plastic enclosures. They’re sometimes called ‘bubble babies’, because they’re so susceptible to infections that even contact with the mother or father could cause death. Indeed, these children are then doomed to suffer their entire lives in an enclosure, and still, most of them die at an early age.
Replacing Faulty Genes: First Attempt
Asha’s doctors knew that she would suffer the same fate; that without drastic measures to isolate her from every source of infection, she would probably die in childhood. With little hope for a normal life, 4-year-old Asha became the subject of a pioneering research study.
This was in 1990; this was the first attempt to replace a faulty human gene. Researchers did a blood transfusion. They, then, modified these blood cells with a correct version of the gene and injected the cells back into her body. One can do this with blood, of course, because it’s possible to extract cells and then reinject them into the bloodstream.
The hope was that some of the modified cells would then produce ADA, and that these cells would start reproducing within her bloodstream, and eventually give her a complete supply of blood cells that had the corrected gene. It seemed to work: six years later, Asha was thriving and living a normal life. Her immune system seemed to be functioning normally, and doctors were cautiously optimistic that her condition had actually been cured.
Strategies Used in Gene Therapy
Thus, Asha was the first gene therapy patient, and became something of a celebrity. She was named an honorary research ambassador for the March of Dimes in 1993. She appeared before Congress, in 1994, and was called living proof that a miracle had occurred. For a time, it seemed that gene therapy was going to be the magic bullet of the 1990s. But, as we’re going to see, Asha’s improvement was not so easily explained.
It appeared that Ashanthi DeSilva was receiving regular injections of synthetic ADA at the same time she had gene therapy. Thus, it’s possible that those synthetic injections are what cured her of the disease. And yet, gene therapy remains a hope, for sure, but it’s definitely not a promise at this point, and there are real questions about whether it’s ever going to work for humans.
Introducing Specific Normal Genes to a Human Genome
Understandably, gene therapy—that is, the modification of genetic errors—became an exciting, if very speculative, area of biomedical research after these first experiments. Since then, since about 1990, there have been more than 100 clinical trials for a variety of genetic diseases, affecting hundreds, perhaps thousands, of patients at this point.
The government contributes about a quarter of a billion dollars in research money to these efforts in gene therapy every year. Most of it is administered through the National Institutes of Health, in Bethesda, Maryland, where they provide grant research for people around the country doing this kind of research.
These gene therapy experiments work through gene modification therapies, which adopt a whole variety of disease-fighting strategies. Many of the trials focus on the introduction of specific normal genes to a human genome. There are also other trials that are efforts to make cancer cells more vulnerable to attack, by inserting a gene for a protein that turns on the immune system, and therefore, fights the cancer cells. There are a number of different ideas in gene therapy that are now underway.
Common Questions about Gene Therapy and Genetic Engineering
The straightforward genetic approaches that worked well with bacteria and plants aren’t amenable to humans; they aren’t amenable to other animals. The reason is because animals undergo an extremely complex process of cell differentiation.
Children suffering from combined immunodeficiency disease are often confined to plastic enclosures. They’re sometimes called ‘bubble babies’, because they’re so susceptible to infections that even contact with the mother or father could cause death.
Gene therapy experiments work through gene modification therapies, which adopt a whole variety of disease-fighting strategies. Many of the trials focus on the introduction of specific normal genes to a human genome.
