Basics of Human Gene Therapy

Basics of Human Gene Therapy

Jason Trites

Copyright 1996

Wouldn't it be wonderful if there was no cancer? No heart disease? No blood problems? Everyone wants to be healthy and have a healthy family but some diseases are genetically related. How are these diseases avoided? This question was pondered by molecular biologists and geneticists. What they developed will revolutionize medicine and health care as we know it. The technique used to try to cure these "incurable" genetic diseases is called human gene therapy.

Gene therapy is by no means a new field of scientific query. The idea was first proposed back in the 1950's when Watson and Crick described a model of the double-stranded helix of DNA (Griffith 316). Knowing that DNA is composed of nucleotide base pairs in certain ways, scientists began to ask questions about the DNA structure in the 1970's (Becker) . If the bases can be arranged "incorrectly", then why can't they be rearranged in the "correct" way to produce the desired effect? Genetic experiments involving base pairing went on for years. After these years experiments with bacteria and viruses began. The genetic codes of these cells were changed to express different products like insulin. These products are human based but can be produced by non-human cells. This led to more thoughts and questions. If a bacteria cell can be altered to produce a human product, then why can't a human cell which can't produce this product be altered to produce it also? New experiments began with animals and creatures with larger genomes. Answers formed from the animal experiments. Technical advances occurred to the point that gene therapy could be performed on humans.

Gene therapy has now become a relatively simple process. The basics of the process are the identification of the gene in question, duplication of that gene, and insertion of the gene into the human genome needing the gene (CIS) . The gene that needs to be altered or replaced must be identified. The correctly functioning gene that replaces the defective gene must first be isolated and then duplicated. The gene in question can be isolated by attaching a molecular marker to the gene. The gene is then removed from the genome by a restriction enzyme that will break the genome only at the desired base junctions (i.e. when ATA is next to GAT). Genes removed from the genome can be duplicated easily by PCR. PCR is a process where the genetic sequence of the gene is replicated by the introduction of base pairs in the sequence along with replication enzymes, which induce, cause, and proofread replication.

Next the gene must be inserted into the cell needing it. This can be done either in-vivo or ex-vivo. In in-vivo therapy a vector (generally a retro-virus) is modified with the desired gene and injected into the cells that need the product of the gene. A retro-virus that replicates itself by inducing it's host cell to produce it's genome. The cell host of the retro-virus, after the virus introduces it's genome in the cell, produces the product the retro-virus genome is programmed to produce. Ex-vivo therapy is when the defective cells are removed from the body. The cells are then injected with the gene mechanically or naturally by a vector. The engineered cells are the reintroduced into the organism they were removed from ( Suzuki 176) . New types of gene therapy are being developed now and some day will be applied.

The effectiveness of gene therapy applied in humans is not proven with hard evidence. There are some cases of advocated success but no real evidence. One such case, and the best chance of an effective therapy, is one where two little girls with ADA deficiency were given gene therapy. In 1990 some cells were removed, altered and replaced in the girls (Marshall) . The results of the therapy are good ones except for the fact that the girls were given injections of ADA while the experiments were in progress. ADA production by the engineered cells cannot be measured because of the injections of ADA. The injections mask the production by the engineered cells. These results would be good if the girls were taken off of the ADA injections for a while to see if their cells are enough to produce the necessary ADA ( Marshall) .

Ethical questions about gene therapy have been raised. Should we allow gene therapy to be performed? Can there be possible side effects to the therapies? Is gene therapy a way of playing God? All of these questions are good ones, ones raised every time a new form of medical technology comes along.

Should we allow gene therapy to be performed? With more time and effort put into research gene therapy can become a great tool to doctors. Gene therapy may be unaffordable for some people now, but as the technology advances the of gene therapy will affordable and available to the common citizen. Money will be saved the world over due to less hospital time and more infrequent and shorter treatments. The life of the next president or Nobel prize winner could be saved. Everything that could possibly save a life should be done.

On the other hand people with genetic defects may not want the therapy or feel the therapy should not be given because fate has dealt them this hand and they should play it . Not all people may be able to handle the therapy (either due to the vector or the "foreign" gene reacting with their system.) Many people may feel that if a treatment doesn't work for some people that no one should attempt to take the treatment because of the potential risks. Who wouldn't be willing to risk it to lead a "normal" life?

The possible side effects actually could possibly be predicted. The only possible side effects are a reaction to the vector or to the introduced gene. The vector can be reduced to a protein shell and be inactive as far as it's natural function is concerned. The reaction to the introduced "foreign" DNA in the cell could possibly destroy all attempts to engineer a cell in a person. The bodies defenses could attack the cell because it is genetically different than the other cells similar to the rejection of a transplanted organ. The few side effects or risks are largely outweighed by the possible good the therapy can do.

The problem of geneticists playing God does bring up a serious question; will gene therapy be performed on germinal, reproductive cells or just somatic cells ( Becker) ? If so would these cells be modified to correct defective genes or to produce a "super race" as Hitler wanted to? Questions like these are brought up frequently in ethical and moral discussions. If gene therapy is used only for correcting defective genes then there should be no problem with it ethically or morally. With the possibility of using gene therapy to produce more advanced humans, creating our own piece of evolution, it could be considered that we are playing God (Suzuki 183). The selection and replacement of undesired genes would narrow the gene pool slowly, but narrow the gene pool just the same. The loss of some genes would seem fine at first, but lead to a lower number of heterozygous or hybrid humans which could possibly be better off than either of the homozygotes. The lack of "random" mating would produce the same problems, a loss of genes in the gene pool leading possibly to a loss of vigor or viability (Suzuki 184) . If some genes are therapeutically removed from the gene pool and a new form of disease comes along that is counter-acted by the lost gene what will happen? Will the human race be wiped out? It's doubtful (but possible), the gene would probably show up as a mutation in the population anyway, but who wants to take the chance? Somatic cell gene therapy cannot change the gene pool because it doesn't affect the reproductive cells. Only reproductive cells can pass on their genes to future generations. Somatic cell therapy shouldn't be questioned as a therapy but germinal gene therapy should be looked after and highly regulated. Germinal gene therapy is highly questioned and all the answers seem to be negative. The answers so far are that the proposed advancements are faked due to the large amount of money to be made by developing a method of genetic therapy that consistently work.

Gene therapy is leading in new directions (because of the possibility of saving lives and the desire for the ever powerful dollar). The cells being engineered now are cancer and bacteria cells. Cancer cells are being engineered to be susceptible to certain forms of antibiotics and pharmaceuticals. The engineering allows the antibiotics or pharmaceuticals to destroy the cancer cells. This form of gene therapy and others like it are in their infantile and experimental stages (CIS) . It has been proven to work in laboratory tests but will truly be tested when tried on humans. The possibilities seem endless.

With all the controversy of ethical questions and accusations of non-scientific testing and falsified evidence, the process of gene therapy trudges onward. The technology will be used some day in ways not yet thought of. It is the wave of the future and most people would like to catch this wave for profit or for the desire to create a new technology and help people. Hopefully this type of therapy will be successful and gene therapy will become a common treatment. For the people with heart disease or cancer it would be a miracle and a godsend. The idea of gene therapy is not new and neither are the ideas of what it could do. Gene therapy is going to lead us into the twenty-first century and hopefully carry us through. Out of all of the legal mumbo jumbo (i.e. the FDA) and greedy investors hopefully will come a technology used for good.

Works Cited

Becker, Amy and Soderberg, Erin. "Gene Therapy: the Future of Medicine." 5/22/96. Online. 10/22/96.

CIS, Cancer Information Service. "Questions and Answers About Gene Therapy." 8/93. Oncolink. Online.

Griffiths, Anthony and Gelbart, William and Lewontin, Richard and Miller, Jeffrey and Suzuki, David. An Introduction to Genetic Analysis. Sixth edition. New York: W.H. Freeman and Company, 1996

Marshall, Elliot. " Jury Still Out on Pioneering Treatment." Science. 25 Aug. 1995; pg. 1051.

Suzuki, David and Knudtson, Peter. Genethics. Revised edition. Cambridge, Mass.: Harvard University Press, 1990.

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