The Myth of an 'Addict Gene'

Ten years ago science was said to be homing in on the "alcoholism gene." Could a gene-based cure for addiction be far away?


Well, yes it could. It's very far away, if even possible at all. Researchers now have identified over a thousand genes linked to alcoholism. The genetics of alcoholism mirrors what has become increasingly apparent to geneticists: life is complicated. The way you act or the quality of your health is likely influenced by many genes interacting with each other along with various environmental factors. The concept that a small number of genes are responsible for disease or behaviour is obsolete.


What that means, in the case of alcoholics or drug addicts, is that even if your parents were addicted, it's unlikely that their genes are the deciding factor that will make you an addict.


But many people still hold the outdated, simplified view that key genes "cause" most disease and addiction. And what we don't understand can hurt us. Biomedical ethicists warn that if public policy doesn't catch up with scientific knowledge, then people at risk of addiction will be stigmatized even more than they are now. Life insurance and employment could be denied and genetic screening could stop people 'at risk' of addiction before they are even born.


Life's nose pokes


Genes are information. How that information is expressed within your body depends on diet, stress and even social interactions, researchers say.


"There are almost no examples where genetics works in exclusion of environment," said Dr. Elizabeth Simpson, a geneticist and professor in the department of medical genetics at UBC. In fact, environmental factors "are important not just in the disease itself, but the course of the disease, the severity of the disease and whether it is actually a significant event in a person's life or not," Simpson said.


Recent research has found a way to look at the influence of environmental factors on drug use in lab rats.


Two lines of rats were bred to have different levels of reaction to apomorphine, a derivative of morphine. One breed doesn't react to the drug very much (Weak Drug Response rats), and the other has a strong reaction (Strong Drug Response rats). When cocaine or alcohol was made freely available to the rats, WDR rats drank more alcohol and used more cocaine than SDR rats.


The scientists then looked at the effect of a stressful life experience on drug usage in the rats; they were put into a new cage and poked in the nose.


After the stressful nose poke, SDR rats increased their consumption of alcohol over a prolonged period, while the WDR rats only increased their drinking for a short time. The SDR rats also used more cocaine after the stressful experience than WDR rats.


The genetics of the rats predicted an outcome that was reversed with one nose-poke. Rats that seemed genetically predisposed to drug use before the stressful event ended up using less afterwards, and rats that used less before ended up using more drugs after. If drug use can change so completely with only one event in a rat's life, it's not hard to imagine how chaotic, stressful lives might lead to humans using more drugs or alcohol.


Tangle of genetic influences


"Multiple genes with small effect is really a scientific discovery of the last ten years, which is very challenging in the way we think about genetics, and it's not the point of view the public knows right now," says Dr. Elizabeth Simpson.


There are thousands of genes that have been linked to addiction, most of them relating to how drugs of abuse work in the brain. Other groups of genes have been linked to traits that make up an "addictive personality," like impulsivity, risk-taking and novelty seeking.


Genetics cannot predict whether someone will develop an addiction; at most genetics will identify risk factors. But genetics can determine what therapies have the greatest chance of working.


"The knowledge of the genetic basis of the disease opens up possibility of treatment, and prevents lots of treatments that don't work," says Dr. Simpson.


There are many different ways that addiction can get wired into the brain. Genetic analysis of a person's genes can pinpoint what is most likely to be contributing to that person's addiction problem. For example, genes for processing an addictive drug could be normal while there are deviations in genes involved in feelings of self-esteem. That would indicate that therapies focusing just on blocking the effect of the drug would not be as effective as therapies focusing on self-esteem.


Using genetic information to get a more holistic look at a person's health is where medicine is heading. But before that becomes possible, the cost of a complete analysis of a person's genes needs to come down in both price and manpower.


Ten years ago, scientists were just starting to figure out how to analyze the genes (or genome) of a person, the Human Genome Project was pumping hundreds of millions of dollars into the effort. Ten years from now it is likely to cost a few hundred dollars and a couple days of work.


"Your baby is born, and should you want it, you have their genome sequenced for a thousand dollars," predicts Dr. Simpson. "What's hard about that thousand dollar genome is, what does that information actually mean?"


The gene screen


Addiction cannot be predicted through genetics alone, but researchers are still trying to identify people at risk of developing addiction. This means that genetic tests for risk factors in addiction are likely to appear somewhere down the road. The danger in such a test is that the genetic information will be viewed as a reliable predictor of a person's lifestyle and capabilities, when it isn't. Misinterpretation of genetic information resulting in discrimination is already happening.


In 2002, the Burlington Northern Santa Fe Railway Company in the United States secretly tested its employees for a genetic variation thought to be responsible for carpal tunnel syndrome. The variation did not accurately predict carpal tunnel syndrome and the company paid out $2.2 million in a settlement.


In 2003, a young German woman was denied employment as a teacher because of a family history of Huntington's disease. The examining physician said that the woman was fit to do the job but there was a 'higher risk' of future absenteeism. If the woman did have Huntington's disease, which was not known, then the symptoms would only be likely to gradually appear after 20 to 30 years of teaching.


In 2004, a research team studying genetic discrimination in Canada published a report in the medical journal Lancet stating that people in Canada have also been denied life insurance because of a family history of Huntington's disease. Positive genetic diagnosis of the disease has also caused problems at work for people when employers knew the results of the genetic testing. These cases have lead bioethicists to question the practices of the insurance industry and call for a halt in the use genetic information for both employers and insurance companies.


Even though Huntington's is one of the rare genetic diseases that is based solely on genetics and not environmental factors, it illustrates what could happen to other conditions, like addiction, if they are viewed as being strongly genetically based.


Currently in Canada there are no laws prohibiting genetic discrimination. Insurance companies are free to demand genetic testing and use the results to deny coverage.


'Good' and 'bad' genes


With genetic testing also comes the ability to screen out undesirable genetic traits from the population.


Dr. Tom Koch, a bioethicist and professor at both University of British Columbia and Simon Fraser University in Canada, is concerned that if a genetic test for addiction were developed, children with genetic risk factors for addiction would be weeded out because only fetuses or embryos free of "deviant" genes would be brought to term.


Dr. Koch proposed that screening out unwanted genes is essentially the same as deciding that the world is better off without those genes. So is the world better off without people with a biological susceptibility towards becoming addicted?


If the answer is yes, Dr. Koch points out that people like Dylan Thomas, William S Burroughs, and Miles Davis might not have existed and brought their art and music into the world. All were artists who struggled with substance abuse.


The Assisted Human Reproduction Act, signed in 2004, is the legislation that monitors genetic screening of embryos and fetuses. The law created a government agency to monitor and regulate the use of all genetic reproduction technology in Canada. Even though the legislation has been praised for being very comprehensive and socially accountable, disability rights proponents have called for tighter regulation of genetic screening.


The concerns of disability rights supporters are the same as those outlined by Dr. Koch: that weeding out "deviant" genes would also weed out and devalue the contributions of valuable people that have a disability, or a greater risk of developing an addiction.


By labeling people as "at risk" of addiction based solely on genetics, Dr. Koch says, "you would stigmatize those that were allowed to be born, on the basis of genetics that is not their fault, and which may or may not be problematic in the way they live."