GENE THERAPY

The field of molecular genetics is progressing at a rapid pace, with our ability to manipulate genes and understand the complex processes involved in genetics developing on an almost daily basis. Understandably, people have fears about this powerful technology and are worried that we may use it in ways to change our humanity. In particular, gene therapy is one aspect of molecular genetics that is causing a lot of concern.

Gene therapy is defined as a way of curing or preventing disease by changing the behavior of a person's genes. Currently, gene therapy is still in its early stages, with most of it still experimental. There are actually two types of gene therapy: somatic and germline. Somatic gene therapy targets genes in the soma, or body cells. In this way, the genome¹ of the recipient² is changed, but this change is not passed on to the next generation. For example, experimental trials in treating cystic fibrosis³ treat the genes only in the cells of the lungs, and, consequently, the patient's children would still be at risk of the disease. In germline gene therapy, genetic changes are made to reproductive cells. The egg or sperm cells of the patient are genetically changed with the goal of passing on these changes to his or her children. In practice, this would mean changing the fertilized egg-the embryo⁴ — so that the genetic changes would be reproduced in every cell of the future adult, including the reproductive cells. In fact, the use of germline genetic engineering on human embryos is illegal in most countries. Thus far, the procedures are still deemed too risky. Nevertheless, scientists continue to experiment on mice and other animals in order to observe the effects of the treatment and to better understand gene functions more generally.

Many people falsely assume that germline genetic engineering is already performed all the time, due to news reports about genetic manipulation. But in fact, most of these reports are either of somatic gene therapy trials or of cloning, which in itself does not alter any genes but merely copies them. Furthermore, even in the field of somatic gene therapy, many factors have prevented researchers from developing successful therapeutic techniques.

The first problem is in the gene delivery tool—that is, how a new gene is inserted into the body. Scientists have tried to remove the disease-causing genes and insert healthy genes for therapy instead. Most vehicles used these days are viruses. Although the viruses can be effective, other problems may arise. Often, the body reacts against the virus in an immune and inflammatory⁵ response. Additionally, the viruses don't always target the intended areas.

Another obstacle to successful gene therapy is our limited understanding of gene function. Scientists don't know all the functions of our genes and only know some of the genes involved in genetic diseases. Also, many of the genes involved in genetic diseases may have more than one function. For example, sickle-cell anemia is a genetic disease that is caused by an error in the gene for hemoglobin, the oxygen-carrying protein in our blood. A child with two copies of this faulty gene will have this disease, but a child with only one copy of the faulty gene will not. The prevalence of this disease is greatest in Africa, where there is also a deadly form of malaria⁶.

Studies have reported that in areas where malaria is endemic⁷, children with a single copy of the sickle-cell gene had a survival advantage over children who inherited two healthy genes. They went on to grow up and pass on their genes to their own children, conferring on⁸ them their resistance to malaria. Initial studies have suggested that the gene that causes the defect in sickle-cell hemoglobin also produces an enzyme that repels plasmodium-the pathogen that causes malaria. The point is that this secondary gene function was discovered quite by accident.

Finally, environmental factors play a pivotal role in the expression of many diseases. This is illustrated in studies with identical twins—two people with identical genes who have not developed the same diseases. Epigenetics is an entire subfield that has been developed to study how factors outside of our DNA can interact with genetic traits. But, as environmental factors are much more difficult to study, progress in epigenetics tends to be slow.

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Artificial Chromosomes

In an attempt to develop new gene delivery tools, researchers have been experimenting with introducing an extra, artificial human chromosome to the body, which would make forty-seven in all. This chromosome would exist alongside and be independent of our other forty-six chromosomes. Scientists also think that these artificial chromosomes would not be attacked by the body and hence would not cause some of the negative reactions that virus vehicles do.

In fact, Chromos Molecular Systems, a biotech company in Canada, is already producing artificial chromosomes in the hope that this will lead to further advances. Dr. Gyula Hadlaczky, the pioneer of this research at Chromos, makes these artificial chromosomes by modifying normal human chromosomes. The result is called an artificial chromosome-although it was originally created through natural processes-because it is the result of that manipulation.

Although gene therapy is limited at present, Hadlaczky expects these modified chromosomes to have applications in other forms of biotechnology and genetic engineering. One application of this tool may be to alter mammal cells grown in the lab so that they become natural producers of vaccines or other drugs.

Although some critics of genetic engineering fear such technology and think it might lead to mutations and the weakening of living systems, the scientific consensus holds that such general fears are unfounded. And at Chromos, they are optimistic. They point to evidence that their artificial chromosomes do not damage cells and that this is an important step forward in genetic engineering.