By Andrea Blake
Imagine, being the parent of a child, who has already succumbed to the incredible statistics of a childhood disease, and be told your child was part of an even smaller percentile that will affect the medication's reactions in his body. Possibly rendering him unable to recover. Or even worse, not being told of your child's special condition, and him dying from a treatment that was supposed to cure him.
This question is what has brought about the emergence of a field of science known as pharmacogenetics. Scientists are able to link particular genes to how patients will respond to medication - specifically, whether the drug will help them and whether they will suffer side effects. (1)
Pharmacogenetics may be a small stream in the torrent of biomedical research, but its importance is disproportionately large. Pharmacogenetics provides a perspective on individuality of drug response. This individuality has profound implications both for the conduct and interpretation of basic and applied research and for the clinical practice of medicine and pharmacy, where treatment is, after all, administered to individuals. (2)
The beginnings of pharmacogenetics was in the mid-1950's with the demonstration that two unrelated drug reactions were caused by different genetically determined biochemical aberrations: single-gene responses to succinylcholine and primaquine. "The field underwent a renaissance in the 1970's when Vesell and his collaborators demonstrated by drug metabolism studies that identical twins were more alike than non-identical twins for many drugs tested. (Vesell, 1973)" (3) Multifactorial inheritance was postulated with the implication that multiple unknown genetic determinants affected drug disposal. The twin studies suggest that those rare individuals representing the extremes of the normal distribution owe their deviant response largely to genetic variability. From this it can be concluded that genetic factors are an important explanation for variability in response to most drugs.
To this day there are already many gene alterations known that affect a drugs' effectiveness. Asthma patients can be tested for the gene that causes Albuterol or Ventolin to become ineffective. Childhood leukemia which is normally treated with Thiopurines can actually lead to severe bone marrow depletion because the drug cannot be metabolized. Codeine is a very popular pain relief drug for most people, however those with a mutation of their alleles of a specific gene receive no comfort due to the fact the body cannot convert the drug into its active form. Tuberculosis is usually successfully treated with a drug family know as Isoniazid, however in some, they metabolize the drug so fast it isn't absorbed. A very common drug used these days to treat depression is Prozac. Unfortunately in some people, the drug is metabolized so slowly it can reach toxic levels. Another drug that could cause severe harm is Procainamide. This drug is usually used for heart conditions, however when the drug isn't cleared properly from the body, it leads to fatal liver disease (1). All of these drug reactions are quite severe, and all of these drugs are quite commonly prescribed without much forethought by the doctor.
Pharmacogenetics also raises perplexing marketing, safety, and regulatory issues. Many Pharmaceutical companies are teaming with research centers to develop connections between certain ailments and the drugs that heal them. At Georgetown University in Washington, D.C., Raymond Woosley, chair of the pharmacology department, says he and his colleagues have been working with Affymetrix of Santa Clara, California, to develop a rapid screening procedure for CYP mutant genes (carcinogenic genes); some of which occur in up to 7% of the population. Woosley's staff now routinely screens patients in clinical drug trials for these mutations. (4)
Myriad Genetics, a genomics company in Salt Lake City, is developing a diagnostic that may let physicians better customize how they treat patients for hypertension. Hypertension is most commonly cause by high salt intake. Myriad has developed a test for mutants of the angiotensinogen gene, which codes for a protein that regulates salt retention. The test is being evaluated in a large clinical trial at the U.S. National Institutes of Health. If patients with angiotensinogen (AGT) mutants are helped by a low-salt diet, Myriad could hope to bring the AGT test to market. (4)
A psychiatric geneticist of the University of Toronto is aiming at an entirely different target : mutant receptors for brain chemicals. For the past year James Kennedy has been studying 180 patients with schizophrenia to see whether individuals who have a mutant gene for a dopamine receptor are less likely to be helped by the anti-psychotic drug clozapine. (4)
While these lines of research offer patients and physicians the possibility of precisely tailored treatments, they could be a mixed blessing for pharmaceutical companies. One fear is that pharmacogenetics will shrink the market for a particular drug by limiting who can take it. Drug companies also worry that drug development might be slowed if the agencies charged with regulating new drugs begin requiring pharmacogenetic data. (1)
Despite such concerns, several large drug companies are improving their pharmacogenetic programs. Some companies believe that "There's a real threat to any pharmaceutical [company] that doesn't incorporate pharmacogenetics. Your market could be taken away from you."(Lee Babiss of Glaxo Wellcome) (4)
There are also many ethical questions that follow these procedures. It isn't simply to do the test or not, but who pays for it, who is it made available to, who are the results given to, what is the insurance company's role in all of this? I think that privacy also plays a large role in factoring the ethics of screening a person's genetic makeup. Not only do these tests enable a doctor to predict the reactions of a drug to a specific patient, but it also predicts the possible future of the patient. Screening for drugs like Codeine or Prozac is one thing, but screening for cancer or Alzheimer's is another. If a gene screen shows that you are in the percentile that does not respond to codeine, then a doctor will prescribe you another pain killer; if the same screen shows that you have a high probability of developing cancer later in life, it will most definitely affect the way you live and who insures you. Insurance companies make money off of healthy people, if it is known that you have a high risk of contracting a monetarily expensive disease, then an insurance company will most likely not insure you. This could lead to a lot of possible problems with heathcare.
However, there is a flip side to this. If it is known that you have a high chance of developing a certain ailment, such as Alzheimer's, then it would be possible to hopefully prevent the onset of it. If pharmacogenetics continues it's research, then a drug could be developed to hinder the onset of many ailments.
Unfortunately both of these choices cost money. Money to fund the research for the gene screen and money to develop the drugs. That money has to come from somewhere. The initial money will come from grants, government and private funding. Nevertheless the money must be made back somewhere. That is where the consumer, you and me, come into play. How much should the insurance company pay? Should they pay for the screen? For the medicine? How much should the individual pay? What about those that cannot afford the tests and drugs? These questions are very difficult for one person to answer. Are the tests going to be so expensive that only the rich can afford to have them done?
Chances are the tests will be less expensive than the potential treatment of an ailment. From an insurance company's view, this would benefit them, if there was a known cure or preventative measure the patient can take. Unfortunately this also means that the insurance company will know if you will be a costly customer. With this knowledge, they could raise your prices, or even worse possibly reduce your coverage. Essentially there is a very fine line between necessary knowledge and too much information. People may also not want to know they will be developing cancer later in life, if there is nothing they can do about it. Why would you want to know your fate before it happens?
All in all, the study of pharmacogenetics brings up a lot of ethical questions in the retail portion of science. But also brings a lot of vital information to the world of scientific discoveries of understanding the cause and effect of the human body.
1. Begley, Sharon, "Screening for Genes." Newsweek Feb 8, 1999:66
2. Deitrich, Richard A., Erwin, Gene, McClern, Gerald E, "Development of animal models as pharmacogeneic tools", proceedings of a workshop, December 4-6, 1978, Boulder, Colorado / sponsored by the Alcoholic Research Center of the University of Colorado and the National Research Centers Branch, NIAAA
3. Motulsky, A.G., "Pharmacogenetics and Ecogenetics" Human Genetics Supplement 1: 1(1978)
4. Cohen, Jon, "Developing Prescriptions With a Personal Touch" Science Feb, 1997:776
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