WASHINGTON _ What does a roving spouse have in common with awandering mind?Easy: Both traits reportedly stem from highly conserved genes _ if,that is, you believe Time magazine. "Infidelity: It may be in ourgenes," trumpets the latest edition. Last month, the magazine drewessentially the same conclusion about attention-deficit disorder.The theory, which some call "genetic determinism," is nothing new. Itlies in a highly controversial realm of science known as behavioralgenetics, which aims to penetrate the molecular biology of such diverseand complex traits as homosexuality, scholastic achievement,criminality and dementia.The increasing popularity of the theory has led David Reiss, a GeorgeWashington University psychiatrist to declare in the journal Sciencethat "the cold war is over in the nature vs. nurture debate."That does not mean it's time for the biotech industry to begin workingon genetic prescriptions for brutishness or promiscuity.Nothing in nature is that simple _ and nothing brings a skepticalbehavioral geneticist like Tim Tully to a boil faster than the implicationthat such complex behaviors can be ascribed to one gene or another,without taking into account the profound environmental influences thatalso play a significant role in human development.Tully, a senior scientist at the Cold Spring Harbor Laboratory in NewYork, has read the Time article on attention-deficit disorder, and he'sstill fuming. "That's the dangerous situation the press is at right now,"Tully says. "They bought the genetic determinism argument, hook, lineand sinker _ and don't even offer alternative explanations any more."Peter Breggin, director of the Center for the Study of Psychiatry, inBethesda, Md., and one of the most vocal critics in the field goes a stepfurther."Behavioral genetics is the same old stuff in new clothes," he toldScience. "It's another way for a violent racist society to say people'sproblems are their own fault because they carry `bad' genes."Tully and other behavioral geneticists think nay-sayers like Breggin gotoo far, and point to evidence suggesting that there is a genetic basis fora spectrum of behaviors, among them Alcoholism and Tourette'ssyndrome.Dean Hamer, of the National Cancer Institute, said "all of us wouldagree that what you would like to have in the end is a quantitativeassociation between a person's genotype and their behavioralphenotype."But, though a quantitative explanation has eluded researchers in mostcases, a few "extreme types of behaviors" including Alzheimer's andHuntington's disease are "very firmly established," Hamer says.Scientists cite three bodies of research that have kindled an increasedinterest in behavioral genetics:u A vast body of information on the genetic underpinning of behaviorsin animals, chief among them the relatively simple fruit fly Drosophilamelanogaster. Over three decades, for example, Seymour Benzer of theCalifornia Institute of Technology has found a gene, per, whichgoverns the fly's circadian rhythms. Flies who lack the gene arehealthy, but they behave differently than normal flies.u Improved studies in humans. A series of studies that are frequentlycited are twin studies done by Thomas J. Bouchard at the MinnesotaCenter for Twin and adoption research. Bouchard's team has examinedalmost 1,000 pairs of twins, fraternal and identical. Of those pairs 128were raised in different homes. Bouchard found that identical twinsresembled one another more than they did their surrogate relatives.u Mounting evidence that the relationship between genetics andbehavior is infinitely more complicated than Time magazine wouldhave its readers believe. "The current theoretical models of behavioralgenetics are too simplistic," Tully says. "They assume that single genesact alone without any influence from other genes or environmentalinfluences."Tully said the concept of nature vs. nurture comes from the theoreticalequation: "genotype plus environment equals phenotype.""That equation is oversimplified," he said, because it understates therole of environment. As a result, much of the experimentation inbehavioral genetics is "misguided" and likely to yield results that aredifficult, or impossible, to replicate.For the equation to mirror reality, it should read: genotype plusenvironment _ plus a non-additive term which is the interaction ofgenotype times environment _ equals phenotype."The experimental models at worst simply eliminate that term from theequation," he said. "As soon as you include it, you can no longer parsephenotype into purely environmental or purely genetic effects."The influence of the environment can be so powerful that it canameliorate the effects of one of the most profound genetic defects,phenylketonuria (the accumulation of an amino acid resulting in mentalretardation and other complications). "In practice," Tully said, "wedon't cure that problem with any genetic manipulation. We cure it byremoving phenylalanine from the babies' diet _ which is anenvironmental manipulation."If we raise them in an environment with phenylalanine, they areretarded. If we raise them in an environment without phenylalanine intheir diets, they are normal. So how can you talk about purely geneticdeterminism?"With such a complex combination of factors at play in humandevelopment, it should come as no surprise that researchers have hadgrave difficulties in identifying specific genes and the roles they play inbehaviors.Another problem is the likelihood that not one but dozens _ or evenhundreds _ of genes are involved in complex behaviors. To study theinfluence of genes on behavior, then researchers must first understandhow the genes influence one another, and then factor in the effect ofthe environment.Depression and schizophrenia are two well-known examples of clearlydefined conditions whose genetic underpinnings have perplexedscientists for decades, according to a recent article in Science. Eachtime a research team has produced evidence linking particular genes orchromosomal regions with one of these illnesses, the investigators havehad to withdraw their findings because no one else could replicatethem.Nevertheless, the research continues _ and every so often yieldstantalizing results. For instance, Hamer of the National Cancer Instituteand four colleagues reported a year ago that homosexuality may belinked to a region on the X chromosome known as Xq28. Hamer saidhis team is in the process of trying to replicate their earlier study, andthat the preliminary findings are promising."We're also looking at sexual orientation in women, and there the storyis more complicated," he said. If there is a genetic basis for femalehomosexuality, his team has not yet unmasked it.And a Dutch American team led by Han Brunner of the NijmegenUniversity Hospital has linked monoamine oxidase A deficiency,which produces borderline retardation and such criminal behaviors asrape and arson, to a mutation of a gene on the X chromosome.Tully and some other researchers, including Peter Schonemann, apsychologist at Perdue University in West Lafayette, Ind., suggest thefrustrating pace of progress may be due, in part, to methodologicalproblems _ particularly the assumption that scientists can break abehavioral trait down into clear-cut genetic and environmentalinfluences.Define Gene-Gene Interaction First"Gene-gene interaction is the rule, rather than the exception," Tullysaid. "You cannot define the contribution of a single gene to thebehavior unless you can also define gene-gene interactions. In order todo that you have to know the specific alleles carried at every genelocus involved in a specific interaction. If you don't know all the genesand can't describe gene-gene interactions, you will grosslyoverestimate the contribution of a single gene. This can be provenmathematically."Tully recommends proceeding in precisely the opposite direction.Working with fruit flies, he breeds strains with different alleles of thesame gene, groups the flies according to the different alleles, and thenstudies differences in learning and memory.So far, he said, the work has yielded a handful of genes _ "fewer thana dozen" _ that appear to be involved in these processes, although hedeclined to discuss the work in detail. If he succeeds, he will tease outthe sequences of these genes, and then, "in 10 years," begin looking forhomologous genes in humans.The key of that experiment will be to draw blood samples at randomfrom a diverse population, he said. Then divide the subjects into groupspurely on the basis of the sequences of the alleles of the suspect gene."Once you do that, and have groups divided up according to whetherthey have allele a or allele b at chromosome X, only then can you beginto analyze behavior", Tully said.Practical applications of this research are far off, scientists said. Still,the effort could provide medicine with tools for managing some verypersistent and perplexing disorders, including Tourette's syndrome,alcoholism and the dementias. n
-- Steve Sternberg Special To BioWorld Today
(c) 1997 American Health Consultants. All rights reserved.