Geneticists have not only identified genes that cause genetic disease, but they have also developed genetic tests to detect these diseases as well as researched possible cures for them.

Some people who have a family history of a genetic disease such as Tay-Sachs or cystic fibrosis may get a genetic test to see if they carry the mutated gene that causes the disease. For cystic fibrosis, Tay-Sachs, sickle cell, and many of the other genetic diseases, a simple blood test is all that is needed to detect the mutated gene. This is called preconception genetic testing and counseling. If both partners carry the recessive trait, this may influence the couple’s decision about whether to have a biological child together. Blood tests and cytogenetic analysis can also detect chromosomal abnormalities, such as translocations, that the parents may carry. Once a woman is pregnant, there are also genetic tests that can be performed on the unborn baby. This is called prenatal genetic testing. Amniocentesis is one of the tests that can be performed. During an amniocentesis, a needle is stuck into the mother’s abdomen and into the amniotic sac. Some of the amniotic fluid that surrounds the baby is drawn out through the needle. To make sure there is enough amniotic fluid to take out a sample and still leave enough behind for the baby, amniocentesis is not done until a woman is 16 to 18 weeks pregnant. The test is only done if there is some reason to believe that the baby is at a higher risk for developing a genetic disease because the test itself carries a small risk of miscarriage.

The amniotic fluid can be tested for diseases such as cystic fibrosis, Tay-Sachs disease, and sickle cell disease, as well as for chromosomal abnormalities such as Down syndrome, translocations, and deletions. Scientists in a laboratory look at the baby’s chromosomes and prepare a picture of them called a karyotype. They can rule out Down syndrome by counting the number of chromosomes and making sure there are not three of chromosome 21. They can also detect structural abnormities in chromosomes, such as translocations (balanced and unbalanced), deletions, duplications, and inversions, by comparing the banding patterns of the chromosomes. Not all genetic testing is limited to before birth, however. People who, for example, have a family history of Huntington’s disease can also be tested. And, even though cancer is not an inherited disease, some of the genes that predispose women to breast cancer can be inherited. There are genetic tests to detect the mutated genes for breast cancer, too.

But not everyone with a family history of an inherited disease is convinced that they would like to know what their genetic future holds. Why not? Keep in mind that there is no cure for Huntington’s disease and that sufferers die in their late forties or fifties. Would you want to know that you carry a disease that could affect the rest of your life? What if there was a possible cure? Would that factor into your decision making? What if you were planning to have children? Knowing that Huntington’s disease is inherited in an autosomal dominant manner, would you then want to know? Everyone has their own opinions and must make their own decisions about these issues. Some people will want to know and others will not. There is no right or wrong answer to these questions. They are your genes.

About 1 in 10 people is born with a genetic disease. While scientists have developed medications and other medical interventions that may reduce the symptoms of some genetic diseases, the only true way to cure a genetic disease is to replace the mutated gene in every cell of the body.

On September 14, 1990, a four-year-old girl named Ashanthi DeSilva became the first person to receive gene therapy. Ashanthi suffered from a rare genetic disease called severe combined immunodeficiency, or SCID (pronounced skid). Patients who have SCID do not produce an enzyme called adenosine deaminase (ADA), which is needed for the body to make T and B cells (also know as lymphocytes, which are an important part of a healthy immune system). Before the development of gene therapy trials, there were only two ways to treat patients with SCID: frequent injections of the ADA enzyme (similar to insulin injections), or a bone marrow transplant from a compatible donor. If neither of these treatments worked, the only way children with SCID could live was in an artificial, completely
germ-free environment. In 1971, David Vetter, a boy from Texas, was born with an X-linked form of SCID. He lived inside a bubble for 12 years, his entire life, while he waited for a cure for his disease. David became known as the “bubble boy.” For this reason, SCID is often called the “bubble boy” disease.

When David was born, doctors hoped to be able to cure his disease by doing a bone marrow transplant. In this procedure, the patient’s own bone marrow is killed by chemotherapy or radiation and then replaced with the healthy bone marrow of a compatible donor. If the donor does not have a matching tissue type, the patient’s body may reject the bone marrow cells. A matching tissue type is often found in one of the patient’s siblings. The more siblings a patient has, the greater the possibility of finding a matching tissue type. Even if the donor is compatible, there is still a risk of the patient developing graft-versus-host disease. In graft-versushost disease, the healthy bone marrow tissue that is transplanted (the graft) into the patient (the host) attacks the patient’s body. If this happens, the patient has to take drugs to suppress the new immune system that is now growing inside their body. However, suppressing the immune system leaves the patient open to infection again.

Doctors had been unable to find an exact bone marrow tissue match for David, but something needed to be done. David was very unhappy living in the bubble. So on October 21, 1983, a month after David’s 12th birthday, David’s doctors and his parents decided to transplant some bone marrow cells from David’s older sister into his body. At first, David’s bone marrow transplant seemed to be working, but in December of that year he became very sick, and he died in February 1984.

Doctors discovered later that David’s sister’s bone marrow contained the Epstein-Barr virus (EBV), which is the same virus that causes mononucleosis, or mono. Most people have been exposed to the Epstein-Barr virus at some point during their lifetime. The virus can cause symptoms such as fever, sore throat, and swollen lymph glands. Once a person is infected, the virus stays in the person’s body for life and is dormant (inactive). In some very rare cases, an EBV infection can lead to the development of Burkitt’s lymphoma, a type of cancer. Unfortunately for David, he had never been exposed to EBV, and when doctors autopsied his body after death, they discovered that he had tumors all over his body. David died from the Burkitt’s lymphoma. His death led scientists to discover that some viruses can cause cancer.

In 1983, gene therapy was not available to David. But SCID was a good test case for gene therapy for several reasons. First of all, only one gene is malfunctioning in the disease and that gene is small. And all of the symptoms of SCID disappear if the gene can be replaced and start functioning on its own. Finally, alternative treatments such as bone marrow transplants and injections are expensive and risky. To deliver the correct gene into the body’s cells, scientists use a vector (carrier). Scientists have tried several different viruses, including retroviruses (HIV, the virus that causes AIDS, is an example of a retrovirus, but it is not used as a vector) and adenoviruses (like the ones that cause the common cold). To make the vector, the parts of the virus that cause people to get sick are disabled. The corrected gene is then added to the virus’s genome. Once this virus infects the patient, it delivers the corrected gene into the patient’s cells.

In ex vivo gene therapy, doctors take cells from a patient, coax an engineered virus with a healthy copy
of the gene to infect those cells, and then return the cells with newly healthy genes to the patient.

Seven years after David Vetter died, Ashanthi DeSilva received gene therapy that doctors hoped would cure her SCID. Although she did better than David, she was not completely cured of the disease. As long as she was receiving injections of the correct gene, Ashanthi did well, but as soon as the therapy was discontinued, symptoms of her disease returned and she still had to take medication that delivered ADA to her body. The gene therapy that Ashanthi received targeted her T-cells, which die after a few months. In 2002, Italian and Israeli doctors figured out that if a SCID patient’s own bone marrow stem cells were taken out of their body and the corrected ADA gene was added to those cells, and then the patient’s own bone marrow was partially killed (like in a bone marrow transplant), the gene therapy worked better. Unlike T-cells, stem cells live throughout the patient’s life instead of dying after a few months. Doctors treated two patients with this method in 2002, and after a year, both patients had fully functioning immune systems. Both patients now live normally. One of the patients was even exposed to chickenpox, a disease that would definitely have killed her before the gene therapy, but she was able to fight it off just fine.

In 1999, 18-year-old Jesse Gelsinger was the first person whose death was attributed to gene therapy. Jesse was being treated at the University of Pennsylvania’s Institute of Human Gene Therapy in Philadelphia for a rare metabolic disease when he died. Doctors said that the treatment triggered a severe reaction, which caused many of Jesse’s organs to stop functioning. Scientists stopped gene therapy trials for a time after Jesse’s death so they could figure out how to prevent this from happening again. X-linked SCID patients have been helped by gene therapy, but this has not been without problems. In 2000, 15 French SCID patients were treated with a retrovirus containing the corrected ADA gene. Ten of the 15 have been cured of SCID, but 3 of those 10 boys developed T-cell leukemia, a cancer of the bone marrow that involves the T-cells. Scientists know that retroviruses randomly insert their DNA into the host’s DNA. They hypothesized that the retrovirus given the boys with SCID may have integrated its DNA into the middle of a proto-oncogene, causing the boys to develop cancer. One of the boys died. The other two seem to be cured of SCID, and their cancer is now in remission (not detectable at the moment, but it may come back at some point later). In December 2007, another little boy undergoing the same gene therapy in London was also diagnosed with leukemia.

In light of these tragedies, scientists are being very careful about how they proceed with gene therapy. If they can get the procedure to work, it could mean the difference between an early death (or a severely limited life such as David Vetter’s) and the chance to live a normal life for the many people who live with a genetic disorder.

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Genetics-based medicine is not limited to gene therapy. In 2001, the FDA approved the first genetics-based drug, Gleevec, which is used to treat chronic myeloid leukemia (CML), a type of blood cancer.

CML patients have a translocation between chromosomes 9 and 22. The translocation occurs when a piece of chromosome 22 breaks off and attaches to the bottom of chromosome 9. A tiny piece of chromosome 9 also breaks off and is transferred to the bottom of chromosome 22. The tiny chromosome 22 that results is called the Philadelphia chromosome, named after the city in which researchers first found out that all CML patients carry this translocation.

The breaks in chromosomes 9 and 22 occur within some important genes. When the pieces of chromosomes 9 and 22 fuse back together, they form an oncogene that codes for a protein that causes the bone marrow to make too many white blood cells (which are also abnormal), causing CML. Gleevec blocks this protein, stopping the abnormal growth of white blood cells and keeping the CML under control.

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Who should have access to genetic information? For example, if a 20-year-old woman’s father is diagnosed and dies of Huntington disease and she decides to get tested for the mutated Huntington gene, should her insurance company be told the result of those tests? What if the test is positive? The woman and her insurance company now know that she will most likely get sick in the next 10 to 20 years. It is possible that insurance companies could discriminate against people with positive genetic test results by refusing to cover them. Some states have passed laws forbidding this kind of discrimination, but the laws differ from state to state. If the person being tested is under 18, should his or her parents know? Parents may be able to help a child cope better with the results of a genetic test. But, on the other
hand, this information may lead the parents to treat the child differently.

What about current and future employers? Should they be told the result of a genetic test? It might help if they know what is happening in case the employee gets sick while at work. But this could also prevent them from hiring an employee in the first place. So, who should know?