Marilyn is Confused about the Biology of Alcoholism

Marilyn is Wrong Copyright © 1999-2005 Herb Weiner. All rights reserved.

Ask Marilyn ® by Marilyn vos Savant is a column in Parade Magazine, published by PARADE, 711 Third Avenue, New York, NY 10017, USA. According to Parade, Marilyn vos Savant is listed in the "Guinness Book of World Records Hall of Fame" for "Highest IQ."

In her Parade Magazine column of October 12, 2003, Marilyn explained why she doubts that certain people are genetically prone to alcoholism.

Rebuttal to Marilyn's views on the genetic basis of alcoholism

Dr. Charles E. Booth booth@easternct.edu, Department of Biology, Eastern Connecticut State University, supplied the following information:

Marilyn wrote:

"One reason is that alcohol doesn't exist in nature. Instead, alcohol is a creation of mankind: Our genes don't know about it..."

She is wrong on all counts here:

  1. Alcohol (ethanol) does exist in nature - it is produced by yeast and other microorganisms, as well as some plants (Ref: Nelson, D.L. And M.M. Cox, 2000, Lehninger Principles of Biochemistry, 3rd ed., Worth Publishers, NY, page 544).

  2. Some vertebrate animals also produce ethanol, for example, goldfish exposed to low levels of dissolved oxygen in their water (Refs.: Johnston, I.A. And L.M. Bernard, 1983, Utilization of the ethanol pathway in carp following exposure to anoxia, Journal of Experimental Biology 104: 73-78; http://www.st-andrews.ac.uk/~fmrg/documents/69.pdf; Rausch, R.N., L.I. Crawshaw, and H.L. Wallace, 2000, Effects of hypoxia, anoxia, and endogenous ethanol on thermoregulation in goldfish, Carassius auratus. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 278: R545-R555; http://ajpregu.physiology.org/cgi/content/abstract/278/3/R545)

  3. The famous Belgian lambic beer is made by exposing the wort to the open air so it can be colonized by wild yeast (Ref: http://ourworld.compuserve.com/homepages/pvosta/pcrbier1.htm). Humans certainly developed methods for distilling alcohol to make it more concentrated, but they start with ethanol produced by natural fermentation.

  4. There are published scientific reports of birds and primates feeding on over-ripe, fermenting fruit containing ethanol and displaying signs of being intoxicated. In fact, the August 2004 issue of Integrative and Comparative Biology (volume 44, issue # 4) contained eight peer-reviewed review article from a research symposium devoted to alcohol production, consumption, and physiological effects in nature (Ref: http://www.findarticles.com/p/articles/mi_qa4054/is_200408); the reports of birds and primates consuming alcohol, and the possible biological basis for alcoholism, are discussed in several of the articles in this volume.

  5. Our genes don't literally "know" anything, but we, and other vertebrate animals, do have a gene coding for an enzyme, alcohol dehydrogenase, that breaks down ethanol in the body (the same gene produces ethanol in yeast and in hypoxic goldfish). Most of our alcohol dehydrogenase is found in our liver cells ( Ref: Nelson, D.L. And M.M. Cox, 2000, Lehninger Principles of Biochemistry, 3rd ed., Worth Publishers, NY, page 544). However, there is also some alcohol dehydrogenase produced in our stomach (Ref: Parlesak, A. et al, 2002, Gastric alcohol dehydrogenase activity in man: Influence of gender, age, alcohol consumption and smoking a Caucasian population. Alcohol and Alcoholism Vol. 37, No. 4, pp. 388-393, 2002; http://alcalc.oxfordjournals.org/cgi/content/abstract/37/4/388).

  6. The fact that animals in the wild consume and metabolize alcohol, and in some cases seem to be attracted to it, opens up the possibility that alcoholism could have biological, that is, genetic, roots. This idea has been put forth in the so-called "drunken monkey" hypthesis (Stephens, D. and R. Dudley, 2004, The drunken monkey hypothesis: the study of fruit-eating animals could lead to an evolutionary understanding of human alcohol abuse. Natural History, December 2004). I don't necessarily subscribe to this concept (Here is are some criticisms of the hypothesis: http://www.save-the-elephants.org/Elephant%20News%20Items/Of%20Drunken%20Elephants.htm), but it is a legitimate area of scientific investigation (albeit a hard one to resolve).

Marilyn wrote:

"Another reason is that about 80% of alcoholics are male. Yet, no one suggests that problem genes are sex-linked, such as male-pattern baldness."

Once again, she is mistaken on the facts of biology, and also suffers from seriously flawed logic:

  1. So-called "male-pattern baldness" is not sex-linked - it results from an autosomal (non-sex chromosome) gene that expresses itself in males that are heterozygous for the trait (and the condition is probably influenced by androgens, or male sex hormones of which testosterone is one), but not in females (Ref: Fraser, F.C. and J.J. Nora, 1986, Genetics of Man, 2nd edition. Lea and Febiger, Philadelphia. Page 132).

  2. I don't dispute that the majority of alcoholics are males (though the 80% figure is higher than that reported by the National Institutes of Health). Researchers have identified some physiological differences in the way males and female respond to alcohol (Ref: Parlesak, A. et al, 2002, Gastric alcohol dehydrogenase activity in man: Influence of gender, age, alcohol consumption and smoking a Caucasian population. Alcohol and Alcoholism Vol. 37, No. 4, pp. 388-393, 2002; http://alcalc.oxfordjournals.org/cgi/content/abstract/37/4/388).

    And there may well be social and psychological factors that influence male alcohol consumption patterns. But, that does not negate the possibility that one or more genes predispose certain people to alcoholism.

  3. The National Institute of Alcohol Abuse and Alcoholism of the National Institutes of Health states the following on its website:

    Research shows that the risk for developing alcoholism does indeed run in families. The genes a person inherits partially explain this pattern, but lifestyle is also a factor. Currently, researchers are working to discover the actual genes that put people at risk for alcoholism. Your friends, the amount of stress in your life, and how readily available alcohol is also are factors that may increase your risk for alcoholism. (http://www.niaaa.nih.gov/FAQs/General-English/faq3.htm)

    I'm much more inclined to believe the scientists at the NIH than I am Marilyn. And to support my belief in the scientific research, I have appended a list of genetic markers correlated with alcoholism (see below). Note that these markers are mostly neurotransmitters or receptors for neurotransmitters that presumably influence how a person's brain responds to blood alcohol; a person with certain version of one or more of these gene (that is, a certain gene allele) could be predisposed to alcohol dependence.

Marilyn wrote:

"So I am concerned that, in an effort to remove the stigma of alcoholism from individuals and to blame their genes instead, we are stigmatizing whole families and ethnic groups. In my opinion, that's far worse."

This is one of the more egregious example of flawed logic I have encountered from a supposedly intelligent person: Undesirable social consequences may well be a valid reason for making policy decisions, but they cannot be used to establish scientific understanding of a topic (that is, scientific facts).

Bottom Line: I don't know if alcoholism is genetically-determined or not - but it is certainly a possibility that cannot be dismissed out-of -hand, especially not using the flawed reasoning given by Ms. Vos Savant.

Genetic Markers Correlated with Alcoholism

Genes for Neurotransmitter Receptors

dopamine receptor, subtype 2 (DR2)+: In a sample of 35 alcoholics, 69% had the A1 allele and 31% had the A2 allele. In the same number of non-alcoholics, only 20% had the A1 allele and 80% had the A2 allele. This study suggested that the A1 allele of the dopamine receptor is associated with alcoholism. Reviewed in Blum et al., American Scientist, March-April, 1996. However, other studies have found no association between human Taq1 A1 allele and alcoholism. Town et al., Am. J. Med. Genet., 88:58-461, 1999.

GABA receptor, beta-1 (GABA-R-B1)+: A polymorphism in GABA receptor, type beta-1 (GABA-R-B1) was associated with type II alcoholism but not controls. Parsian et al., Am. J. Med. Genetic., 88(5): 533-538, 1999. Another study of three DNA sequence variants in exons 1a1, 7, and 11 of the GABA-R-BR1 found that none of the genotypes varied significantly among alcoholics and controls. However, trends towards an excess of the exon 7 and 11 polymorphism was found in the entire sample of alcoholics. Sander et al., Psychiatr. Genet., 9:69-73, 1999.

GABA receptor, subtype A alpha 6 (GABA-R-A-alpha-6): A low level of response to alcohol was associated with a polymorphism GABA receptor, subtype A alpha 6 gene. Subjects with a Pro/Ser polymorphism in the GABA-R-A-alpha-6 receptor were alcoholics and had the lowest response level to alcohol. Schuckit et al., Biol. Psychiatry, 45:647-651, 1999.

opiate receptor, type mu: Association between a functional coding variant in the human mu-opiate receptor and alcohol dependency. Town et al., Am. J. Med. Genet., 88:58-461, 1999; Shinka, et al., Mol. Psychiatry 7, 224-228.

serotonin receptor, type 1B (5-HT1B): Transgenic mice were engineered which lacked the serotonin receptor, type 1B (5-HT1B). These null mice showed enhanced aggression. See, also, Entry under Aggression. They also showed altered release of serotonin from several, but not all, brain regions. The receptor-deficient mice were evaluated for their response to ethanol. Mutant mice voluntarily consumed about twice more ethanol as wild-type mice. Their intake of food and water, however, was normal. Mutant mice also took longer to develop ethanol tolerance but showed equivalent response to ethanol withdrawal and metabolism. These results suggest that the 5-HT1B receptor plays a role in the regulation of ethanol consumption, as well as mediating its ataxic effects. Crabbe et al., Nature Genetics, 14:98-101, 1996.

serotonin receptor, subtype 3 (5-HT3): A mouse overexpressing the 5-HT3 receptor in the forebrain was created by introducing a 5-HT3 gene under the control of a calmodulin promoter. Overexpression of the 5-HT3 receptor resulted in a decrease in alcohol consumption and an enhanced sensitivity to the stimulating effects of a low dose of alcohol, without altering its sedating effects or alcohol metabolism. Engel et al., Psychopharmacology (Berl.), 140:243-248, 1998; Engel and Allan, Psychopharmacology (Berl.), 144:411-415, 1999.

serotonin transporter (5-HTT or SERT): A low level of response to alcohol was associated with the LL polymorphism of the 5-HTT gene. Schuckit et al., Biol. Psychiatry, 45:647-651, 1999. Genes for Neuromodulators and Enzymes

neuropeptide Y (NPY): Neuropeptide Y (NPY) is a thirty-six amino acid neuromodulator which is expressed throughout the nervous system. NPY's action is mediated through the Y1, Y2, and Y5 family of receptors, G-protein coupled receptors which inhibit the production of cAMP. NPY- deficient mice were produced by genetic engineering. These mice showed an increased preference for ethanol as indicated by a high ethanol consumption. The sedative effects of ethanol were reduced in NPY-deficient mice as compared to controls. The increased ethanol consumption in NPY-deficient mice was not related to a preference for other flavored solutions nor was it calorie-driven. Mice were also genetically-altered to overproduce NPY. In contrast to mice who were deficient in NPY, overproducers drank significantly less ethanol than controls. Thus, high levels of NPY are associated with low ethanol consumption and increased sensitivity to ethanol while low, or null, levels of the neuromodulator are correlated with high ethanol consumption and lowered ethanol sensitivity. Thiele et al., Nature, 396:366-369, 1998.

monoamine oxidase A (MAOA): Monoamine oxidases are enzymes that catalyze the oxidative deamination of monoamines; MOAs are vital to the inactivation of monoaminergic neurotransmitters such as serotonin and dopamine. A positive correlation was found between two polymorphic markers in the monoamine amine oxidase A gene (a mutation in exon 14 and (CA)n repeat ) and alcoholics with antisocial personality (ASP). Genomics, 55(3):290-295, 1999.

catechol-O-methyltransferase (COMT): Catechol-O-methyltransferase (COMT) is an enzyme involved in the metabolism of dopamine, epinephrine, and norepinephrine. Two alleles of the COMT gene have been identified which result in functional differences in COMT activity. One allele codes for low (L) activity and the other encodes a high (H) activity enzyme. The frequency of the L allele was markedly higher in adults with late onset (type 1) alcoholism as compared to the general population, suggesting that the the low activity COMT polymorphism contributes to the development of late-onset alcoholism. Tiihonen et al., Mol. Psychiatry, 4(3):286-289, 1999. Family studies also indicated that the L allele was seen observed more frequently in males with early-onset alcoholism, than family members who did not inherit the L allele, suggesting a role in early-onset alcholism, as well. Wang et al., Mol. Psychiatry, 6:109-111, 2001.

http://www.wiskit.com/marilyn/alcoholism.html last updated December 29, 2005 by herbw@wiskit.com

Page last modified by Herb Weiner Sun Oct 14/2007 20:23