The Genetics of Alcoholism:

A Review of the Evidence and Ethical Implications

Jennifer N. Guggenheim, Medical Student, University of Colorado Health Sciences Center

Consider a time in the future when a hard-working bus driver with a perfect driving record is fired after his company tests his DNA and finds that he has a genetic predisposition for alcoholism. Although he is not an alcoholic and never has been, his DNA indicates that he has genes that make him vulnerable to alcohol dependence. Despite the fact that he has been a dependable driver who has never abused alcohol, his company terminates him. He loses his job not because of his behavior, but because of his DNA.  

Now consider the fact that on May 14, 1988, a repeat drunk-driving offender sped the wrong way down the highway in his pickup truck and slammed head on into a school bus. The bus burst into flames killing twenty-four children and three adults while injuring thirty others (MADD 1998). Perhaps the driver of the pickup truck also had a genetic predisposition to alcoholism. If a DNA test had been available to him so that he had known of his vulnerability before he developed a problem with alcohol, maybe this tragedy could have been prevented. These two scenarios demonstrate the ethical dilemma of DNA testing that society may soon face. It is unfair that the hard-working bus driver be discriminated against for something he has never done; but it is also unfair for a drunk driver to destroy the lives of others.  

Several lines of evidence lead us to believe that there is a genetic component to the risk for alcoholism (Cloninger, Bohman, Sigvardsson 1981; Pickens et al 1991; Kendler et al 1992; Schuckit 1994). Most recently the Collaborative Study on the Genetics of Alcoholism (COGA) reported "highly suggestive" evidence of a genetic vulnerability for alcohol dependence (Long et al 1998). This study points to specific chromosomes that predispose individuals to become alcoholics. As researchers further delineate the biological basis of alcoholism, they will be able to develop more effective treatment programs and initiate preventative programs. This in turn would benefit the millions of people who are affected by alcoholism and its devastating effects.  

At the moment, DNA tests for vulnerabilities to alcoholism do not exist. However, such a test may become available in the not-too-distant future. DNA testing is complicated, not only because of the scientific methodology, but also because of problems like health care discrimination, job discrimination and stigmatization. To better understand the ethical issues of the genetics of alcoholism, this paper will discuss important information about alcoholism: First, it will define alcoholism. Second, it will demonstrate how society is affected by it. Third, it will outline the scientific research and discoveries that have been made about alcoholism. And finally it will discuss the ethical implications of the genetics of alcoholism. There are five main ethical issues: autonomy, privacy, justice, equity and quality (Knoppers, Chadwick 1994). By sensitively educating health care workers, policy makers and the general public about these issues, the quality of life will be improved for individuals suffering from alcoholism and those who are affected by it. 

What is alcoholism?  

The word alcoholism has many different connotations. It is important to first establish a firm definition for alcoholism before focusing on the ethical implication of the genetics of alcoholism. The Joint Committee of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine established one that clearly defines alcoholism: 

Alcoholism is a primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. (Morse, Flavin 1992) 

This is the definition of alcoholism that is presently used by clinicians and researchers. It takes current concepts into account.  

The most recent criteria used by clinicians to diagnose alcohol dependence are set forth in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Alcohol dependence is described as "a maladaptive pattern of alcohol use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same twelve-month period": 

(1) tolerance 

(2) withdrawal  

(3) alcohol is often taken in larger amounts or over a longer period than was intended  

(4) persistent desire or unsuccessful efforts to cut down or control alcohol use  

(5) great deal of time spent obtaining, using and getting over the effects of alcohol  

(6) important social, occupational or recreational activities are given up or reduced because of alcohol consumption  

(7) continued use despite psychological or physical problems caused or made worse by alcohol 

These essential features make dependence differ from abuse and harmful use. While all can be problematic, dependence (often referred to as alcoholism) is considered the most severe alcohol use disorder.  

How does alcoholism affect us? 

Eighteen million Americans are alcoholics (Noble 1991). These individuals impact our work force, our fiscal budget, and the safety on our highways. The economic cost of alcoholism and alcohol abuse to the United States in 1992 (the latest year for which all sufficient data are available) was $148 billion (National Institute on Alcohol Abuse and Alcoholism (NIAAA) 1998). While the monetary cost can be estimated, the emotional toll to victims can not. In 1997, alcohol was a factor in 39.3 % of all traffic fatalities and resulted in the death of 16,520 people (MADD 1998).  

These statistics demonstrate the tragic effects of alcoholism. To combat this, scientists have been studying alcoholism to learn about its mechanism. This could lead to better prevention programs for those at risk and improved treatment programs for alcoholics. As we learn more about the genetics of alcoholism, ethical issues are created that must be addressed. While it is important to stop the negative consequences of alcoholism, we must be aware that new ethical concerns are being created. We hope to protect people from the ravages of alcoholism, but we must also protect individuals who may have a genetic vulnerability from being discriminated against or stigmatized.  

Family, Twin, and Adoptee Studies 

The fact that alcoholism runs in families has been well-documented in studies since the 1950's (Heath 1995). Individuals who have a family member suffering from alcoholism are five times more likely to struggle with the disease themselves (Cloninger, Bohman, Sigvardson 1981)). Family studies have found genetic factors contribute to early-onset alcohol dependence (Lewis, Bucholz 1991; Mathew et al 1993). However, family studies do not indicate whether or not alcoholism is transmitted genetically or through family environment. In order to separate these factors, scientists have conducted twin and adoptee studies.  

Twin studies have indicated inheritance in alcoholism (Kendler et al 1992; Pickens et al 1995) Identical twins are monozygotic (MZ) and share 100% of the same genes; fraternal twins are dizygotic (DZ) and share only 50% of their genes. MZ and DZ twins share the same environment. Therefore if MZ twins are more similar to each other than DZ twins are to each other, these similarities can be attributed to the fact that MZ twins have identical DNA whereas DZ twins do not. Twin studies investigating alcoholism have established that there is a substantial genetic influence on alcohol consumption patterns (Heath, Martin 1993).  

Adoptee studies have provided an opportunity to examine individuals reared by biologically unrelated parents. They compare the risk to biological relatives with the risk to adoptive relatives of alcoholics. The risk of alcoholism in adopted-away sons of alcoholics is four times greater than for the general population (Cadoret 1987). While these studies do not indicate that genetics are the only factor in alcohol dependence, they do imply that genes create a vulnerability that can be affected by environment.  

Family, twin and adoption studies demonstrate the genetic contribution to alcoholism but also confirm an important environmental component. While learning about these components may allow us to develop new preventative measures, the ethical implications of these findings must be carefully considered (Ball, Murray 1994). 

The Promise of Molecular Genetics 

In 1989, the National Institute of Alcohol Abuse and Alcoholism (NIAAA) initiated the Collaborative Study on the Genetics of Alcoholism (COGA), a large-scale, multidisciplinary research program to investigate the genetic components of the susceptibility to alcohol abuse and dependence (Begleiter et al 1995). Recently, COGA reported highly suggestive evidence on chromosomes 1 and 7 and more modest evidence on chromosome 2 for linkage to alcohol dependence vulnerability. The researchers also found a protective locus on chromosome 4 near alcohol dehydrogenase (ADH) genes (Reich et al 1998). In a separate study conducted by NIAAA, highly suggestive evidence for linkage emerged for genomic regions on chromosome 11 and 4 (Long et al 1998). While the two studies identified several different regions, both found evidence of a linkage to chromosome 4. This concurrence demonstrates the strength of evidence that a region on chromosome 4 is linked to alcoholism. What does the suggestive evidence mean? Of the approximate 100,000 genes that make up each individual's DNA, scientists suggest that certain areas contribute to alcoholism. In the not-too-distant future, the exact gene or genes within these areas will be replicated, cloned, and available for research. 

Alcoholism is a complex, heterogeneous disorder (Morse, Flavin 1992). It has environmental, social, and genetic predisposing factors. The chance of a single gene causing a vulnerability to alcoholism is unlikely. Instead, a polygenic model involving multiple genes is more plausible (Ball, Murray 1994). That is, there is not one single locus that is responsible for vulnerability to alcoholism, but instead a combination of different genes working in concert. The recent suggestive evidence makes it imperative to explore appropriate rules and policies about the genetics of alcoholism.   

Environment and Biology  

Enoch Gordis, director of the National Institute on Alcohol Abuse and Alcoholism, or NIAAA reported "There is no doubt that genetics play a role in alcoholism... We have twin and adoption studies going back 25 years that prove this. But do we say that it is only genetic? Of course not. Social issues, family issues and environment all play out. We know that some people are loaded genetically, but obviously they can't become alcoholic unless they take a drink (Judge 1997)." 

Consider a man with a strong genetic vulnerability to alcoholism and who lives in Saudi Arabia. In this Arab nation, the consumption of alcohol is strictly prohibited. Foreigners who break this law are deported. Nationals who are convicted of this offense are sentenced to spend time in jail (personal communication, staff member at the Embassy of Saudi Arabia, May 1998). Therefore, this man would not have an opportunity to drink. Consequently, he would most likely not develop a drinking problem. Now consider a man with this same genetic vulnerability born into an environment where alcohol is easily accessible and consumption is encouraged. The chances of this individual developing alcohol dependence are much greater. Conversely, if this man is not loaded with genes that make him vulnerable to alcoholism and he lives in an alcohol rich environment, he will probably not become an alcoholic.  

Alcohol dependence has a genetic component, but an individual's susceptibility also corresponds to the social issues, family issues and environmental influences that he or she may encounter. Some scientists have estimated that genetic factors and environmental factors contribute about equally to the development of alcohol dependence (Heath 1993). But whatever the exact contribution of these factors, it is the combination of a physiological vulnerability to alcoholism and an environment that promotes the consumption that causes alcoholism.  

Medical Genetics  

Scientists have developed ways to test for specific detrimental genetic susceptibilities. For instance, several tests detect preventable diseases that would otherwise cause death or permanent impairment. Prenatal testing can identify Down syndrome and neural tube defects. This information allows parents to make informed decisions about management of these pregnancies (personal communication, Prenatal Diagnostic and Genetics Counseling University of Colorado Health Sciences Center, June 1998). Newborn screening can identify errors of metabolism such as phenylketonuria (PKU) and galactosemia. Without identification of these metabolic abnormalities and rapid interventions, the carriers of these genes would become severely mentally retarded. (Khoury, Beaty, Cohen 1993). 

Through the study of genetics, researchers have learned more about the mechanism of disease and ways to prevent and treat certain disorders. This has been invaluable for those individuals whose lives have been improved by this information. However, there are discrepancies between the ability to detect disease-susceptibility genes and the ability to provide effective interventions. Huntington's disease illustrates this dilemma. Individuals who have this defective gene are not symptomatic until they reach adulthood. An individual with an affected parent has a 50% chance of being affected. However, for those who are identified as having this gene, there is no known therapeutic intervention (McDougle 1996). Therefore, if genetic testing reveals the presence of the Huntington gene, the person who has been tested will have to live with this knowledge but not be able to alter the course of the disease. Genetic information can dramatically change decisions about pregnancies, as well as plans for the present and future. Because of this, it is important to consider the ethical implications of genetic testing. 

Why test for alcohol vulnerability? 

Knowledge is power. If researchers learn more about vulnerabilities to alcohol, they will be able to create prevention programs and improve intervention and treatment programs. For this reason, it is important to identify genes that contribute to alcohol dependence. In addition, accurate diagnosis of risk for developing alcoholism could allow better planning for the future by patients, family members, and health care providers. Today, many people seek genetic counseling to help them prevent or treat a variety of genetic disorders. Through counseling, they learn about their disorder and decisions they can make to best manage their lives. Understanding their disorder and learning about risks that can aggravate their susceptibility allows individuals to positively change the course of their lives. If a test were developed that could test for alcohol vulnerability, individuals for whom this test was positive who would have the advantage of seeking out counseling and prevention programs before they developed problems with alcohol.  

As mentioned earlier, the economic cost of alcohol abuse and alcoholism to the United States in 1992 was $148 billion dollars. In contrast, a single DNA test may cost $200-$450 (Bird, Bennett 1995). If individuals in high-risk categories were tested, and they were able to access genetic counselors and preventive treatment programs, the cost to society of alcohol abuse and alcoholism both financially and emotionally would decrease significantly. 

Fears about DNA testing: Discrimination and Eugenics  

DNA testing information could be used by life and health insurance companies and even governmental agencies to discriminate against individuals who test positive for certain genetic vulnerabilities and disorders. The advent of genetic testing raises the possibility that at-risk individuals could be excluded from private health care coverage (Post et al 1997). This has occurred in the past. Insurance companies have been known to exclude "preexisting conditions" from their coverage (Bird, Bennett 1995). Employers might also discriminate. In attempt to reduce their company's potential health-related costs, they could choose not to hire individuals with a genetic predisposition (Post et al 1997). They might exclude these individuals from their work force due to fears that genetic vulnerabilities could result in a loss of productivity or increased health insurance premiums. This type of discriminatory treatment by insurance companies and employers would have a detrimental impact on many citizens. They could lose the opportunity to work and be insured even if they did not have a problem with alcohol. Having a vulnerability to alcohol does not turn the carrier of these genes into an alcoholic. Thus, these individuals should not be punished for crimes they have not committed. 

There is another basis for fears about DNA testing. In the past, heinous crimes have been committed against people in the name of eugenics. According to a report in the New York Times, "Up until the 1970's some 60,000 people had been sterilized in Sweden, and 11,000 in Finland, under government policies designed to rid the population of properties like poor eyesight and Gypsy features" (Wade 1997). Would it be possible for this to occur again or for individuals with a vulnerability to alcohol dependence to be violated in this manner?  

Ethical issues that need to be addressed 

The advent of DNA testing and advances of the National Institute of Health's Human Genome Project have stimulated reports, guidelines and even some legislation. A consensus has emerged about important ethical issues for the field of genetics. Five fundamental principles underlie this consensus: autonomy, privacy, justice, equity, and quality (Knoppers, Chadwick 1994). This paper addresses these five terms as they are relevant to the genetics of alcoholism. 

1) Autonomy - 

Individuals should have the right to decide to be tested or not to be tested for a vulnerability to alcoholism based upon appropriate information. The nature of genetic testing is highly personal and can have a powerful emotional impact. For this reason, testing should be completely voluntary. Prenatal testing or testing of children should be considered in depth as it may violate both the fetus' and the individual's right to decide. While scientists are learning more about alcoholism and trying to develop effective treatment programs, they have not yet discovered a "cure". Therefore, knowledge of one's predisposition to alcoholism would not ensure prevention or treatment. Given the current imprecise nature of genetic testing for this disorder, these considerations are imperative. To provide the best understanding of all these complex issues, genetic testing should always be accompanied by counseling.

Confidentiality of genetic information is crucial. Consent must be given for any information released to others. As discussed earlier, insurance companies, employers and others could misuse genetic information about vulnerability for alcoholism. Genetic testing should be prohibited both in the workplace and by insurance companies. While test results reveal information to the person who has been tested, other family members may also be impacted. For these reasons test results should be disclosed only to the person being tested.  

3) Justice - 

Children and mentally incompetent adults should be included in the decision to have their DNA tested whenever possible. Whether it is appropriate to test someone for a vulnerability to alcoholism should be rigorously considered. Individuals should have the right to consent to the testing or to refuse. Children may be too young to give informed consent. Ramifications for testing of children who are up for adoption should be addressed. Will these children be less desirable and hence unadoptable? 

4) Equity - 

Access to genetic testing for a predisposition to alcoholism should be equal for everyone. Would individuals of lower economic status have their access to genetic testing linked to their willingness to terminate a pregnancy? Would welfare benefits be denied if an individual refused to be tested? This is especially relevant to certain ethnic groups that have a higher occurrence of alcoholism. While access should be equal for everyone, it is important that no contingencies be linked to the testing procedure. Anyone who wants to be tested should have that opportunity. The results should be confidential and the person being tested should not be required to abort a fetus, give up a job, or change insurance policies because of the results of a genetic test. 

5) Quality - 

Control of test quality is necessary to ensure that individuals being tested for a genetic vulnerability to alcohol are receiving accurate information. "There is an accelerated trend toward commercialization of DNA technology" (Khoury, Beaty, Cohen, 1993). This trend is motivated by profit. It neither reflects an equal  understanding of test interpretations, nor appropriate application. For these reasons, testing should be limited to providers who have appropriate credentials and are obtaining accurate results. 

What can be done to prevent a bus-driver from being fired because of his DNA and at the same time protect children on a school bus from an accident caused by a drunk driver? Social policies and rules need to be implemented that will prevent the misuse of genetic information that exposes predisposition for alcoholism. At the same time social policies must protect the general public from individuals in sensitive positions who could expose a risk to public safety. Three policies should be implemented that would do this. 

The first would establish guidelines concerning DNA testing. A policy must be implemented to assure private, accessible and personally sensitive testing. Consider a woman who wants to have a DNA test to see if she has a vulnerability for alcohol dependence. A policy should be created so that she has access to DNA testing under certain conditions: She has family members who are alcoholics or some other indicator of risk. She is old enough, mentally capable, and makes the decision of her own free will. There are no external pressures to terminate a pregnancy, quit a job, or act in any way she does not choose of her own free will. The test provides high quality results. She sees a genetic counselor prior to testing to understand the test and its implications. And finally, she has access to prevention, intervention, and treatment programs.  

The second would prevent discrimination based on results from genetic testing. Employers and health insurance companies should not have access to genetic testing results, nor should they be able to mandate testing by their employees. Results should be confidential. If an employer or insurance company were to learn of these results, the individual should be protected from any misuse of this information.  

Finally, the third policy would help to protect public safety. This would not be done by endorsing genetic testing for alcoholism. We should not rely on genetic testing to protect the public. Instead public safety would be safeguarded by strictly enforcing current laws and creating new legislation. How would this policy be enacted? Individuals who are placed in highly sensitive jobs and whose actions could detrimentally affect the safety of others (e.g. like airplane pilots and nuclear engineers) could pose a threat to public safety if they drink alcohol while they work. In order to safeguard the public, employers should assume that some of their employees will develop alcohol dependence and should take precautionary measures accordingly. By making the assumption that some and therefore potentially all employees could cause a risk to the public, random drug and alcohol screening procedures should continue to be administered to those who work in highly sensitive positions. In instances where routine testing is not being administered, employers should consider its benefits. Individuals who violate policies about not drinking while they work should receive treatment options as well as punishment. Genetic counseling services should be offered to these citizens to empower them. However, these individuals should not be excused for their alcoholism. Repeat offenders should be prosecuted and face harsh penalties such as jail time, fines and loss of driver's licenses. By enforcing these policies, individuals would continue to be punished for their behaviors, not their genetic vulnerabilities. 

Education could prevent misuse of genetic information 

We must educate our society about the genetics of alcoholism and the ethical issues that surround it. This will help to prevent the misuse of genetic information by those who do not understand its significance. The best way to do this is to target three levels: health care workers, the general public and policy makers (Juengst 1994). On one level, health care workers will need to be educated. They will be the interpreters of genetic results and help individuals learn about their vulnerability. It will be important to provide training to these clinicians so that they are adequately prepared to handle their patientsí new needs. An increase in the number of genetic counselors will be essential to the forward-thinking attitudes that need to be established. On a second level, and just as important, will be the general public. It too must understand the potentials and limits of genetic information. To realize this, we must provide accurate information through schools, in the media, and at a grassroots level. Helping the general public to understand the significance of DNA testing will be one of the best ways to prevent the misuse of genetic information. And finally on the third level, policy makers should learn about this topic. They will be able to influence the publicís responses to genetics advances. And they will be in a position to advocate for citizens who have genetic vulnerabilities and create legislation that will help to protect these individuals. In order for policy makers to properly do this, they must have an improved knowledge of genetic issues. This can be imparted through symposiums and workshops on a local and national level. By targeting health care workers, the general public and policy makers, we will greatly enhance societyís ability to understand genetic testing and deal with it in an appropriate and advantageous manner.  

Conclusion 

Current research results from COGA as well as those from other experts are exciting and give hope to the millions of people who are affected by alcohol dependence. The advances that are being made in the genetics of alcoholism will assist the creation of prevention programs as well as improved interventions and treatment programs for those with vulnerability for alcohol dependence. In the meantime, before these programs are perfected, we may experience an awkward transition period in which diagnostic accuracy improves before effective prevention programs can be implemented. This will raise ethical, legal, social, and procedural issues that may be accompanied by anxiety, depression and hardships for our patients (Bird, Bennett 1995). Taking this into consideration, it will be important that the decision to be tested for a genetic predisposition be made with informed consent and accompanied by counseling. This information must be safeguarded and kept confidential so as not to be misused by insurance companies and employers. Children and incompetent adults must be protected from testing which is performed without their full comprehension and given input into the decision even if their parents or guardian give consent. Finally, the quality of the testing procedure must be monitored and access must be equally available to all.  

Legislation concerning the use of genetic information about vulnerabilities to alcoholism is needed and necessary. We must protect the civil liberties of individuals whose genetics make them vulnerable to alcohol. A hard-working, reliable bus driver with an excellent driving record should not lose his job because a DNA test identifies genes that predispose him to becoming an alcoholic. However in order to safeguard the public, policies should be enacted that will monitor the behavior (not the genetics) of individuals in highly sensitive positions. In this way, we continue to address behavioral issues, not genetic vulnerabilities. By encouraging further discussion of this topic as well as implementing legislation that addresses public and private concerns, we will all benefit. 

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