Biology and Behavior

April 03, 1998


Abstract
By Adriel Bettelheim

How much do our genes drive the way we act?

Nearly every week, scientists report identifying a new gene linked to a particular human trait. The discoveries have provided a clearer understanding of the human condition and offered a starting point for potential cures to cancer, AIDS, cystic fibrosis and a host of other afflictions. But the ability to unravel the mysteries of DNA has led some researchers to look for genetic links to commonplace behaviors, such as sexuality, violence and risk-taking. That has spawned a sometimes passionate debate over how much biology controls destiny and whether society is relying too much on science and discounting underlying social and economic conditions. Policy-makers are trying to sort out the social ramifications and establish ground rules for genetic testing and privacy.


Lab mice have played a critical role in recent genetic discoveries. (Photo Credit: Robert Bishop)

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Overview

Laboratory mice usually are very attentive parents, constantly herding their pups into nests and crouching over the offspring to nurse them and keep them warm. So why would lab mice at the University of Washington start neglecting their young?

Neurobiologist Steven Thomas and molecular biologist Richard Palmiter inactivated a gene in the mice that plays a key role in preparing the brain for motherhood. The gene is responsible for creating a protein needed to manufacture the brain chemical norepinephrine, which is believed to promote nurturing. When the mice with the altered gene gave birth, they left the pups scattered around the cage, not even bothering to remove placental material. Nearly three out of four of the pups died of neglect. But when the surviving pups were given to foster mothers with the normal gene, 85 percent survived.

“It makes sense that maternal instincts would be reinforced in the brain just before they're needed,” Thomas says. [1]

The researchers' work is part of a fast-growing field that is attempting to answer the age-old nature-nurture question: Does biology or the environment play a greater role in determining behavior? More than 130 years after Austrian monk Gregor Mendel formulated the laws of heredity while studying pea plants, researchers continue to disagree over how much genes control destiny and what that means for public policy.

Research in behavioral genetics is different, but no less controversial, than the burst of cloning research that has dominated news in recent months. [2] Though both come under the rubric of “barnyard biotech,” the developmental research does not involve the creation of new organisms. Instead, it explores how genes in DNA carry chemical messages that may influence behavioral traits.

Scientists since the mid-1930s have known that certain mutant genes, acting alone or in combination with one another, can cause hereditary diseases. Technology has since been perfected to identify the precise genetic code for conditions such as cystic fibrosis, Huntington's chorea and Tay-Sachs disease, and, in limited cases, physicians are applying gene therapy to treat symptoms.

But over the last two decades researchers have found ways to isolate and characterize DNA sequences from individuals. With these new tools, some scientists now are searching for biological explanations to far more complex phenomena, such as sexuality, risk-taking and violence.

“There is now a perception that we are closing in on a molecular understanding of the human condition,” writes Tennessee medical researcher R. Grant Steen in his 1996 book, DNA and Destiny: Nature and Nurture in Human Behavior. “Most people are aware that, though genes can determine good health and above-average intelligence, genes are also responsible for many undesirable traits.”

Popular attention to the field was sparked by the publication of the controversial 1994 book The Bell Curve, in which authors Richard Herrnstein and Charles Murray asserted that IQ is largely hereditary. The authors went on to argue that, since people often marry people like themselves, the differences between intelligence of races and classes are growing wider, and efforts to help the poor are likely to fail because poverty is a function of inherited low intelligence. Many scientists disputed the conclusions, charging the authors' statistical measurements were inadequate and that IQ was not a true indicator of intelligence. [3]

Biologists, psychologists and others drawn to the field say they are concerned about drawing similar broad societal conclusions from limited studies that could have weaknesses in methodology. But their work is nonetheless presenting headline-grabbing evidence that genes may account for previously unexplainable, but commonplace, behaviors.

In 1996, a research team reported discovering a link between anxiety-related behavior and a gene that controls the brain's ability to use a neurochemical called serotonin -- the same neurotransmitter targeted by Prozac and other antidepressants. Researchers at the National Institutes of Health (NIH) and the University of Wurtzburg in Germany studied more than 500 people and found that individuals who have a slightly shorter version of the gene for the serotonin transporter tend to be more anxious and harbor more negative thoughts and feelings than those with a longer version of the gene. [4]

That same year, two groups working independently at NIH and in Israel reported a link between excitability, thrill-seeking and quick temper and a gene involved in the activity of the neurotransmitter dopamine, which, among other things, transmits sensations of pleasure. The studies focused on a segment of the gene's molecular code that is repeated either four or seven times in a row. Novelty-seeking seemed more common in people with the sevenfold repetition. [5]

Since then, there have been near monthly announcements of newly discovered suspect genes, often with the caveat that they act in tandem with other genes and the environment to express a trait. Last year, researchers at NIH reported finding that an abnormally long variant of the gene tied to risk-taking could also account for drug addiction. The type of behavior expressed depends on whether the suspect sequence acts in tandem with up to 10 other genes that also might determine novelty-seeking. Someone with two or three active genes might be somewhat impulsive in nature, or maybe drive race cars for a hobby. Someone with all 10 might thrive on risks like taking ######. [6]


Extensive research has also been done on genes believed to be linked to schizophrenia, manic depression and alcoholism. The specific cause of each condition remains unknown, and most serious researchers acknowledge that environment may play as important a factor as genetic inheritance. Indeed, the biological connections are murky enough that scientists in some cases can identify a gene sequence linked to a condition but not be able to explain how it works.

Arguably the most controversial connection between genes and behavior concerns suspected links to crime and violence. Researchers studying a dysfunctional Dutch family announced in 1993 that aggressive behavior may be linked to a single faulty gene that causes a shortage of enzymes needed to break down serotonin molecules that transmit signals in the brain. Since then, scientists and policy-makers have engaged in an often stormy debate over the roots of crime and possible solutions for society. [7]

Proponents of continued research say that while the concept of a single “criminal gene” may be the stuff of science fiction, biological markers exist that could make a person more likely to commit crimes or provide clues about populations that are more at risk. Gene therapy to correct any inborn problems could also make an attractive and humane alternative to incarceration, they argue.

But critics say labeling a group as predisposed to violence recalls the eugenics movement of the early 20th century, which led to the sterilization of convicts and some mental patients in the hope of reducing crime among future generations. Many social scientists say researchers, in a rush to “biologize” behavior, are ignoring environmental influences, such as poverty, broken families and racism.

“We tend to seek quick and easy technological conclusions that aren't always for the public good,” says Dorothy Nelkin, a New York University sociologist. “Clearly, there are some genetic factors that contribute to behavior. But if you read the media, it's all in the genes. It's easier to blame the individual than take up what's wrong with the social system.”

“A lot of biologists are chasing genes. I tell them, why don't you clone the gene for poverty?” says Craig Ferris, a professor of psychology at the University of Massachusetts Medical Center in Worcester. “Things are more complex, and behavior is acted out in a social context. The chemical coding for some molecules isn't going to influence how you get through the day.”

Many researchers in the pro-gene camp are uncomfortable with such criticisms and take pains to note they are only branching out to study specific biological systems, not prescribing broad solutions.

“When you study how a biological pathway works, you know the details, but you're not always able to see the forest from the trees,” says Judith Greenberg, director of the division of genetics and development biology at the National Institute of General Medical Sciences. “You're seeing researchers trying system approaches to more fully understand the complexities of how cells work.”

University of Colorado psychologist Gregory Carey, who has studied the biological roots of crime, says talk about genetic advances is oversimplified and contributes to a misunderstanding of DNA's power, especially when it comes to predicting individual traits.

“We may be able to say a certain percentage of the population is predisposed to a condition, but I doubt we'll ever be able to identify whether Joe Smith will have it or not,” Carey says. “Genes influence differences in behavior, to some degree. But our knowledge is embryonic, and any big headlines have to be taken with a lot of caution.”

The whole concept of discovering a “gene for” a particular condition is somewhat misleading. When researchers identify a gene linked to a trait, they mean they have targeted an “allele,” or a stretch of DNA that has been changed by mutation, that will code for a physical or behavioral trait under normal conditions. But conditions vary, and having a certain allele does not necessarily mean the trait will be expressed. Studies on identical twins, who have the same sequences of DNA, show that one may be predisposed to a condition like schizophrenia while the other isn't, meaning that environment also plays a role. [9]

As researchers continue to study and debate the basis for behavior, these are some of the questions they are asking:

Is criminal behavior more a product of our genes than our environment?

University of Maryland legal scholar David Wasserman endured three years of criticism while trying to organize a conference on genetic links to violence and crime. When 70 biologists, criminologists and social scientists finally gathered at a conference center in Queenstown, Md., in the fall of 1995, some moments resembled a street brawl.

After one panel discussion, a participant accused Wasserman of using pseudoscience to legitimize racism. Soon after, a group of 30 bullhorn-wielding protesters from mental health and civil rights groups disrupted the proceedings, chanting “Maryland conference you can't hide, we know you're pushing genocide.” Wasserman tried to shout down the group, while two other conference participants engaged in a brief scuffle. [10]

The scene illustrated the passions surrounding a debate tinged with racial and political implications. Wasserman, himself skeptical about claims of a biological root for violence, says continued research, if handled appropriately, could make society more compassionate toward criminals. “As a society, we make intermittent efforts to understand and identify with those who engage in conduct that frightens and repels us,” Wasserman says. “It is possible to imagine a society fairer and more humane than our own where findings of individual differences in behavioral predispositions could be used in an appropriate fashion.” [11]

People have pondered links between biology and crime for more than a century. In the 1800s, Italian physicist Cesare Lombroso asserted that anatomical signs of “primitiveness” -- sloping foreheads and prominent chins, among others -- were indications of criminals because crime amounts to primitive behavior. Similar connections are found throughout popular American culture in the first half of the 20th century; the Dick Tracy comic strips, for example, featured villains with physical deformities.

The best scientific work on the subject to date explores the connection between violent behavior and the neurotransmitter serotonin. Groundbreaking research on the Dutch family and subsequent work concluded that low levels of serotonin can contribute to aggressive, impulsive and sometimes violent behavior, including suicide. Many factors influence serotonin production. Males tend to have 20-30 percent less of the chemical than females, and levels tend to fall as one enters adolescence, then rise again as one gets older. Certain diets and consumption of alcohol also can lower serotonin levels.

Scientists have expanded on the work in recent years by looking for similarities in the criminal records of identical twins raised separately and studying chemical changes in the brains of children with attention-deficit hyperactivity disorder. The National Research Council in 1994 reported substantial evidence of genetic links to anti-social behavior but cautioned that the connection “is likely to involve many genes and substantial environmental variation.” [12]


Studies of identical and fraternal twins are giving scientists clues to the relative importance of biology and the environment. (Photo Credit: Twins Day Festival)

A furious debate continues over how to interpret the findings. At one extreme is J. Phillipe Rushton, a psychologist at the University of Western Ontario at London, who asserts that criminality and violence are significantly linked to genes. He argues that blacks worldwide show a higher incidence of criminal behavior because of genetic factors, such as higher testosterone levels and differences in brain size. “If race were an arbitrary, socially constructed concept, devoid of all biological meaning, such consistent relationships would not exist,” Rushton says. “Facts remain facts, and require appropriate scientific, not political, explanation.” [13]

Others insist any exploration of the biology of violence is perilous precisely because it will be exploited to stigmatize groups. Peter Breggin, a Bethesda, Md., psychiatrist and author of the 1991 book Toxic Psychiatry, says the quest is driven by scientists more interested in research dollars than in looking at the society around them. “There's a vast research community hungering for money, and the government and pharmaceutical industry are ready to spend huge amounts of money to convince the public there's something there,” Breggin says. “They don't want to talk to black kids in inner cities or find out why people are shooting each other.”

Breggin helped derail Wasserman's first effort at organizing a conference on genetics and crime in 1992 by organizing protests and charging the meeting was part of a government effort to screen black children and treat them with drugs. That same year, charges of racism prompted the resignation of Frederick Goodwin, then director of NIH's Alcohol, Drug Abuse and Mental Health Administration, after he compared aggressive young blacks to primates in the jungle. [14]

James Gilligan, director of the Center for the Study of Violence at Harvard University, rejects notions that violence is instinctual or hereditary, arguing socially determined gender roles are partly to blame. He says theories of criminal genes are promoted to push a conservative political agenda. “If violence is innate and instinctual, then clearly there is no point in trying to change our social and economic system,” Gilligan writes in his 1996 book, Violence: Our Deadliest Epidemic and Its Causes. “If the assumption is violence is an inextricable part of our inborn 'human nature,' then clearly the only way to keep the problem under control is to emphasize just that: control.”

Several recent and notable findings suggest a complicated comingling of nature and environment may be responsible for aggressive, delinquent behavior. A study of 301 inner-city boys in Pittsburgh found exposure to lead in the environment may be a factor. The study by the University of Pittsburgh School of Medicine builds on previous research showing lead in paints and contaminated soils commonly found in inner cities reduces IQ by damaging brain cells in children. [15]

University of Southern California criminologist Adrian Raine also reports a significant link between birth complications and early maternal rejection and violent crime at age 18. His conclusion: a chain of events begins before conception and continues through one's lifespan that can trigger violent behavior. “There is no single gene capable of producing criminal behavior per se,” Raine says. “But despite strong criticisms from social scientists, empirical data from several sources provide strong converging lines of evidence indicating some degree of genetic predisposition for crime.”

Proposals to screen for specific genes that influence anti-social behavior -- and using gene therapy to treat some conditions -- have caught on with some clinicians. David Comings, director of the department of medical genetics at City of Hope National Medical Center in Duarte, Calif., reports success treating children with nervous tics, hyperactivity and disruptive behavior. The work involves manipulating genes in the frontal lobes of the brain. Left unchecked, such conditions would lead many of the children to drop out of school and turn to alcohol and drugs, Comings maintains. [16]

But the thought of taking matters a step further by screening children at high risk for adult violence and treating them with gene therapy concerns critics. They note predicting violence, even in adults with a history of anti-social behavior, is an uncertain exercise. And pre-emptive strikes by administering drugs to children is regarded by many as both intrusive and expensive.

“Effective education and decent material support are far more important to violence prevention than drug therapy,” says Franklin Zimring, professor of law at the University of California at Berkeley. “We should not be forced to choose only between governmental neglect and ineffectual therapeutic interventions.” [17]

Does society benefit when genetics is used to identify certain traits?

Neurobiologist Evan Balaban has a unique distinction: Last year he made a chicken behave like a Japanese quail. The senior fellow at the Neurosciences Institute in San Diego, Calif., painstakingly isolated brain cells that control sounds and head motions in quail and transplanted them into chicken embryos. When the chicks hatched, they wobbled their heads and crowed like quails, ignored calls from their mother hen but responded to warning cries from quails.

Balaban says his experiments may help stroke victims and others suffering from brain damage. By studying how brain cells come to control inborn behavior, Balaban hopes researchers may eventually train certain healthy cells to take over the functions of cells damaged by disease or injury.

“The first thing you do when you find a gene linked to a condition isn't to call a news conference,” Balaban says. “It's not until much later that you find out whether there's a real link or it's spurious. Researchers who've done work on this for a long time recognize that. The guys who jump from gene to gene to gene don't.”

It's a message frequently repeated by scientists: Developmental biology yields real results that can improve the human condition. But, they caution, it also raises false hopes with sometimes simplistic explanations to complex phenomena, and may provide a new means to intrude on privacy and stigmatize groups.

“People like simple stories, but we're complex creatures,” says National Institute of Mental Health Director Steven Hyman. “For human behavior, there's no single gene that's the equivalent of fate. Genes are critical tools for discovery that are beginning to open real doors to understanding what we are.”

As an example, Hyman points to recent research on autism, a neurological disorder that affects about one in 1,000 children and limits the ability to form relationships. The condition was once thought to be caused by maternal rejection. But in recent years, biologists have zeroed in on a gene that codes for a protein that reabsorbs serotonin into the nerve cell after it has been released. NIH is in the midst of a five-year, $27-million research effort to explore a shorter-than-normal strand of DNA believed to play a significant role in the disorder.

Isolating genes for traits is the first step in the broader process of gene therapy, in which scientists can clone healthy genes to take over for defective ones that cause diseases. [18] The process is expected to set the standard for medical care in the 21st century.

Gene therapy has been sanctioned by NIH for patients suffering from cystic fibrosis, a previously untreatable hereditary disease that causes mucous buildup and infections in tissues, especially the lungs. Seventy percent of cystic fibrosis patients have one identified faulty gene. Scientists are participating in a $40-million research program to spray a solution of virus containing a healthy gene into the nose or lungs of a patient. The hope is the virus will enter the cells of the patient and deliver the healthy gene to compete with the protein made by the faulty gene.

The societal benefits from genetic research extend beyond the treatment of diseases. Police and the FBI increasingly are using DNA extracted from blood, saliva and semen left at crime scenes with DNA profiles in databases. The FBI and state labs recently agreed on technical standards and began pooling data in what some believe is the first step toward establishing an American DNA database. [19] Such a database already exists in Britain and has helped identify repeat sex offenders and other felons. However, big questions remain over who must submit to testing, who can have access to the data and how the DNA samples will be handled.

Despite the advances, many social scientists are concerned that increased reliance on DNA and genes will prompt an Orwellian assault on privacy. Insurers already use family histories to deny coverage or charge higher premiums. If a person's entire DNA map became available in several years, as many researchers predict, insurers, prospective employers and others could use computers to quickly scan for predispositions to certain diseases or personality traits, even an individual's life expectancy.

“Everyone wants to minimize unpredictability,” says Jeremy Rifkin, president of the Washington-based Foundation on Economic Trends and a critic of most new biotechnology research. “A company will want to know if a 38-year-old on the fast track has a predisposition to breast cancer. It has the potential to be a new and virulent form of discrimination.”

The Clinton administration in January said it would send a bill to Congress to prevent U.S. companies from requiring genetic tests in hiring or obtaining genetic information about employees. Several states, including Maryland and Virginia, have passed laws banning genetic discrimination. State lawmakers around the country introduced 153 bills related to genetic privacy last year -- many to prevent employers from using DNA information to deny benefits, according to the National Conference of State Legislatures.

Beyond privacy concerns is the cost to society of overstating the results of DNA research. Near weekly news reports of breakthrough discoveries create false expectations and make society too reliant on science to cure all ills, according to the University of Colorado's Carey. “The average person should walk away with the knowledge that genes contribute to individual differences in behavior; they influence things to some degree, but don't necessarily determine things,” Carey says. “Any big headlines have to be taken with a lot of caution.”

The public was captivated, for instance, by the 1995 discovery of a gene linked to breast cancer. The identification of the defective tumor suppressor gene known as BRCA1 led to optimistic predictions of gene tests that could prolong lives through early detection. But lost in some news reports was the fact that only 5-10 percent of all breast cancer is inherited, and not everyone who has the suspect gene develops cancer.

Researchers worry that such information will be misinterpreted by a mass media intent on harvesting catchy sound bites and quick explanations. Parents in a few years may face the dilemma of subjecting their children to a battery of new genetic tests for a variety of conditions. That could pose troubling dilemmas: If a teenage daughter is found to have the breast cancer gene, should she do nothing, or should she follow the example of some women and have her breasts removed?

“If we have nothing new to offer once the gene has been identified -- well, then what?” asks Malcolm Paterson, a Canadian molecular biologist and cancer researcher. “The serious problem is we have to say to these women, 'We do not know the underlying causes for 70 percent of all breast cancer. We don't know why other women -- those who are not predisposed genetically in ways we are aware of -- develop breast cancer.' ” [20]

Concerns deepen when society uses genetics to make inferences about specific types of behavior. In 1993, NIH researcher Dean Hamer reported a genetic marker for homosexuality -- an aberration on the X chromosome found in 75 percent of gay brothers. The findings, which researchers have not been able to duplicate, caused a tempest and thrust Hamer into a heated gay-rights debate. Some homosexuals felt a biological explanation in the form of a “gay gene” would make society more tolerant of their lifestyles. Others said Hamer was providing ammunition for groups eager to stigmatize gays and lesbians even more.

While many remain divided on the wisdom of studying how biology influences behavior, the federal government firmly backs the work with huge sums of money. President Clinton's fiscal 1999 budget request asked for $13.1 billion for NIH, a 2.6 percent increase over 1998 levels. Of that amount, $12.5 billion is earmarked for research on sequencing DNA and isolating more genes.

The funding priorities are in marked contrast with those in the 1960s and early '70s. In sync with the social psychiatry of the times, NIH in those days spent heavily on finding the roots of behavioral illnesses in conditions such as racism and poverty. “Even 15 years ago, it was common to have purely psychological explanations” for conditions like autism, says Hyman of the National Institute of Mental Health. “Now, we've discovered genes make us vulnerable to serious illnesses. Our challenge is to translate basic discoveries to treatment.”

But New York University's Nelkin predicts that emphasis will gradually eat away at the social welfare system, with policy-makers more willing to accept science-based conclusions and dismantle federal programs to deal with crime and poverty. “Clearly, there are genetic factors that contribute to behavior, but all the talk deals with data,” Nelkin says. “The technical focus masks having to make serious political and moral choices and deal with the real source of things like crime.”

Should the government regulate genetic research?

Unlike telecommunications and the Internet, Washington policy-makers have been wary about regulating genetic research. Many are reluctant to appear to be standing in the way of science and appear more interested in protecting patents of U.S. drugs and technologies that are produced as a result of the work.

Congress in 1996 began to address genetic privacy issues by passing the Health Insurance Portability and Accountability Act, which bars group health insurance plans from denying enrollment based on an individual's pre-existing genetic condition. Insurers are still able to price policies depending on what they know about an applicant's genetic profile.

The Equal Employment Opportunity Commission also has considered whether genetic handicaps are protected by the law. The commission in 1995 ruled genetic susceptibility to a disease is a disability protected by the Americans with Disabilities Act of 1990. Commission members reasoned that rules must allow a level playing field so people born with a disadvantage don't remain at one forever. [21]

Vice President Al Gore began to address this dilemma in January when he announced the administration's bill limiting what genetic information American companies can collect about their employees. “It is clear that cracking the genetic code would be of significantly less benefit if we allow our moral code to become cracked as well,” Gore said in a speech to members of the Genome Action Coalition, which promotes public support of genetic research.

But Heidi Wagner, spokeswoman for the Washington-based Healthcare Leadership Council, which represents concerned employers, said the law proposed by the Clinton administration was too far-reaching because many applications of the research are still unknown. “Genetic testing is so new. My concern is that when the federal government decides to get involved, though well intended, there might be some unintended effects,” Wagner says, adding that existing laws preventing workplace discrimination may suffice.

Gore said the use of genetic testing to predict diseases is already causing prejudice. “The fear of genetic discrimination is prompting Americans to avoid those genetic tests that are now available that could literally save their lives.” [22]

In Congress, lawmakers' attention to genetic research intensified after Chicago physicist Richard Seed announced his determination to clone human beings. At least three bills were introduced in the Senate expressing the belief that cloning a living or dead person was morally indefensible. But the efforts ran into sharp criticism from the biotechnology industry, which said the proposals would block legitimate medical research.

The Senate in February succumbed to pressure from groups such as the American Heart Association and Cystic Fibrosis Foundation and blocked floor debate on an anti-cloning bill backed by Sens. Christopher S. Bond, R-Mo., and Bill Frist, R-Tenn. The bill would have blocked a procedure that allows the nucleus of a human egg cell to be replaced with another cell component, which theoretically could allow an organism to develop in the womb as a human being. Bond and Frist's language thus considered an embryo worthy of the same protection abortion opponents give embryos conceived through fertilization. [23]

Medical groups argued such language could cut off research aimed at cloning cells to treat cancer, heart disease and other maladies. “I don't think Dr. Seed's announcement brought any closer the reality of a human clone,” observes Sean Tipton, spokesman for the American Society for Reproductive Medicine, echoing the sentiments of many biotech groups. “But he may have brought closer to reality the passage of dangerous legislation.”

Anti-cloning lawmakers say their bills are specifically targeted at the cell transfer procedure but allow other types of cloning, such as recombinant DNA technology. “I am extremely reluctant to place any limits on scientific research,” says Rep. Vernon J. Ehlers, R-Mich., a physicist and a member of the House Science Committee, who has authored two anti-cloning bills. “However, while the possibilities of scientific experimentation may seem limitless, there are times when society -- through the governmental process -- can and should place limits.” [24]

As lawmakers grapple with the complex debate, scientists also are trying to establish some ground rules. This year the National Research Council convened a study committee of 10 pre-eminent researchers to define “appropriate uses of new [genetic] discoveries and to clarify ways of thinking about such information.” Committee members, consisting of biologists and social scientists, are expected to make recommendations on the use and misuse of scientific information on human health and behavior and transmit their findings to politicians, the press and public policy analysts, according to council spokesman Dan Quinn.

Ferris at the University of Massachusetts Medical Center says he hopes such efforts will lead biologists and social scientists to collaborate on preventing harmful conditions instead of frequently talking past one another and disagreeing on the root causes. “Part of our American culture is we see a problem, and we want to correct it,” Ferris says. “We're a bright, dynamic society with some of the best science in the world. We should focus on the preventive side, and create more resilient, healthier minds and bodies.”

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Background

Unlocking the Code

The modern research era was ushered in by biologist James Watson and physicist Francis Crick, who in 1953 proposed their now famous model showing DNA composed of two spirally wound chains. The “double-helix” structure demonstrated that a gene carries information written in a kind of chemical code that can be copied and passed on from generation to generation. The genes are packed into sausage-shaped chromosomes that reside in the nucleus of a cell. In the simplest sense, the chemical code dictates the creation of a protein, and the protein controls the expression of a particular trait, such as eye color or blood type.

Gregor Mendel believed all traits can be inherited. He was only partly correct. Scientists have found mutations in individual genes that give rise to specific physical conditions. One is sickle-cell anemia, which is caused by a mutation affecting one blood protein that reduces the ability of hemoglobin to bind to oxygen and distorts the shapes of the cells. Its ability to restrict the flow of oxygen can be fatal.

Most traits aren't as clear-cut, however, and involve complex interactions between a number of genes and the environment. Here, science has its limits. Researchers do not know yet how many genes come together to express specific conditions, or exactly how the genes interact. Moreover, there are myriad environmental factors from radiation to diet that can play important roles.

Separated at Birth

To assess the relative importance of biology and environment, researchers over the last two decades have turned to so-called “split twin” studies of identical and fraternal twins reared apart. Because identical twins come from the same egg and have identical genes, their biological traits should be more similar than fraternal twins, which come from separate eggs. But fraternal twins raised in the same environment sometimes show uncanny similarities -- a convincing argument, some say, that genes aren't everything.

The problem is finding enough separated twins to make a study statistically valid. Some universities have set up “twin registries,” quizzing siblings on a regular basis about everything from religious beliefs to drug abuse and mental illness. Researchers then measure the degree of similarity in the answers. [25]

One study by the University of Minnesota of more than 100 sets of twins reared apart found that identical twins score much more closely than fraternal twins for IQ and psychological traits like extroversion and neuroticism. Researchers also found identical twins raised apart did not score much differently from identical twins raised together. “In the current environments of the broad middle-class, in industrialized societies, two-thirds of the observed variance in IQ can be traced to genetics,” writes David Lykken, a professor of psychology at the University of Minnesota. [26]

Skepticism remains high over twin studies, in part because they describe behavioral variations in a group and cannot be used to predict how an individual acts. Nor do they consistently account for the full and complex influence of the environment, in particular, personality traits from shared experiences, like a war or economic depression.

“These studies are flawed from beginning to end because there are all kinds of suppositions,” says Rifkin of the Foundation on Economic Trends. “There were a lot of legitimate breakthroughs when we began to isolate genes in the laboratory. Now, we've probably shifted too far to the extreme.”

Nature vs. Nurture

The concern about “extremes” is due in part to the connection between the behavioral studies and the eugenics movement of the early 20th century. The movement was founded by Sir Francis Galton, a cousin of Charles Darwin, who asserted in his 1869 book Hereditary Genius that individuals should not get credit for their virtues or blame for their vices because both are beyond their control. Galton also first paired the terms “nature” and “nurture” in trying to explain development.

Galton had the lofty goal of trying to advance aristocratic British civilization. But by the beginning of the 20th century, his followers were subdividing society and singling out certain groups as degenerates, unworthy of reproduction. Many leading psychologists of the time believed that while normal people could control their behavior, the feeble-minded and insane could not.

This led to alarming public policies aimed at cleaning up the gene pool. From 1907 to 1937, 32 American states passed laws permitting the sterilization of the mentally ill, handicapped and those convicted of sexual, drug or alcohol-related crimes. Congress also passed, and President Calvin Coolidge signed, the Immigration Restriction Act of 1924, designed to restrict the entry of persons from Eastern Europe and other areas referred to as “biologically inferior.”

The eugenics movement reached grotesque extremes in the Holocaust, when the Nazis exterminated millions of Jews, Gypsies and psychological patients and set up forced sterilization and selective breeding programs in an effort to purify their gene pool. Revelation of the wartime horrors disgraced the movement and led many researchers to embrace an “environmentalist” school that reached its peak in the 1950s. Adherents argued that human nature was malleable and that all differences among people were related to environment and upbringing. Evolution had little influence, except, perhaps, in making people's brains better at making associations between things.

The pendulum began to swing back to more evolutionary explanations in the 1960s, when psychologists and sociologists began to question whether certain “modules” in the brain aided cognitive ability and the way people learn languages. A school of evolutionary psychologists argued the real question about human society is not why it varies but why it stays the same. Their conclusion: We inherited a common set of psychological mechanisms from our evolutionary past. [27]

Human Genome Project

Advances in laboratory research in the 1970s and '80s -- particularly the ability to insert genes from one species into another, giving the “transgenic” organism a new trait or enhancing an existing one -- finally pushed the debate firmly in the DNA camp and triggered lengthy and expensive explorations of the very essence of biology.

The research so far illustrates both the promise and uncertainties of molecular genetics. Last year, project scientists discovered a new gene linked to the growth and progression of human breast cancer. The gene is found in unusually high levels in tumor cells of most cancer patients. Researchers expect it will help reveal the basic biology of not just breast cancer, but also ovarian and prostate cancer.

Another recent development was the identification of a gene abnormality believed to cause Parkinson's disease, a progressive neurological disorder. The mutation involves one “incorrect” letter in a 400-letter sequence of a normal gene that plays a role in the function of nerve cells.

But eight years after the project began, despite huge costs and the participation of a global team of scientists, it still has not found a single cure for a genetic disease. Project officials defend the scope of the work, saying it will be remembered as a landmark of science.

“Although there is still debate about the need to sequence the entire genome, it is now more widely recognized that DNA sequences will reveal a wealth of biological information that could not be obtained in other ways,” says Francis Collins, director of the National Human Genome Research Institute. “The technology and data . . . will provide a strong stimulus to broad areas of biological research and biotechnology.” [28]

Steen, in his book DNA and Destiny, worries that the current research signals a “reductionist” approach, in which all behaviors are gradually being explained in terms of chemistry and biology. He says that may yet lead to another round of eugenics. Steen points to trends that, taken together, are cause for concern: the ability to screen for medical conditions in the unborn, laws that allow women to abort fetuses with undesirable traits and the ability to use information from genetic tests to discriminate.

“The door is now open to a resurgence of the eugenic ideas that led to such gross excesses in the past,” Steen says. “When people speak of relieving the burden of suffering of the sick, one must ask whose burden is actually being lifted? Any answer other than 'the individual' potentially comes from tainted motives.”

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Chronology

1860s-1940s
Scientists begin to understand the principles of heredity, hastening medical advances -- but also the birth of the eugenics movement.

1865
Austrian monk Gregor Mendel develops the laws of heredity while studying the patterns and relationships of pea plants. The units of inheritance later become known as genes.

1869
British explorer and anthropologist Sir Francis Galton, a cousin of Charles Darwin, founds the modern eugenics movement, presenting evidence that intelligence runs in certain families.

1927
In Buck v. Bell, the U.S. Supreme Court upholds the constitutionality of a Virginia sterilization law. Sterilization laws were passed in 32 states between 1907 and 1937, reflecting public acceptance of using science to improve the quality of the gene pool.

1934
Norwegian chemist Asjborn Folling discovers phenylketonuria, a disorder of body chemistry that, if untreated, causes mental retardation. He subsequently determines the disease is inherited.

1950s-1960s
Researchers unravel the genetic code while a school of psychology asserts human behavior is a response to the environment.

Feb. 28, 1953
James Watson and Francis Crick unveil the structure of deoxyribonucleic acid, or DNA, the material from which genes are made.

1950s
American psychologists Clark Hull and B.F. Skinner modify laboratory animal behavior and develop the concept of reinforcement, or reward, to explain the response to certain stimuli.

1970s
As molecular biologists develop the tools for splicing genes, public-policy groups begin to debate the social and ethical implications.

1974
The Recombinant DNA Advisory Committee is established at the National Institutes of Health to develop guidelines for the safe conduct of gene research.

1978
U.S. geneticists J.C. DeFries and Robert Plomin report there exists a genetic component in lab animals affecting diverse behaviors like learning, sexual activity and aggression.

1980s-1990s
New laboratory advances usher in an era of experimentation.

1980
Religious leaders send a letter to President Jimmy Carter expressing concern about the potential consequences of genetic engineering.

May 22, 1989
The first human gene-transfer experiment takes place at NIH, on a cancer patient.

October 1990
NIH launches the Human Genome Project, a $3 billion, 15-year effort to map and sequence the human body's gene.

1993
Researchers identify genes linked to a half-dozen major illnesses, including Huntington's disease and colon cancer. Human embryos cloned by two U.S. scientists survive for several days in a Petri dish. New findings suggest homosexuality may be inherited.

1994
Richard Herrnstein and Charles Murray draw popular attention to DNA research with their controversial book, The Bell Curve, which asserts IQ is largely hereditary.

October 1995
First human gene therapy trial shows success treating two girls with a rare immunodeficiency disease.

October 1996
Scientists working on the Human Genome Project unveil a map of more than 16,000 genes in human DNA, about one-fifth of the total DNA packaged in chromosomes.

1998
The Clinton administration proposes legislation limiting what genetic information companies can collect from their employees. Congress' attention to genetic research increases in the wake of the cloning controversy.

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Current Situation

'Fountain of Youth' Gene

Scientists have sliced, spliced and transplanted genes to better understand the human condition. Now, they are manipulating them to try to make human cells live indefinitely.

Researchers at Menlo Park, Calif.-based Geron Corp. and the University of Texas Southwestern Medical Center surprised the science world in January when they announced they had altered cells grown in a test tube so that they divide up to 90 times without an abnormality. Conventional human cells divide about 50 times, then die of old age. [29]

The findings capped a 30-year effort to understand a mechanism in living cells that is critical both to the aging process and cancer. The “fountain of youth” is believed to be a rarely expressed gene that creates telomerase, an enzyme responsible for lengthening the ends of DNA that are packaged in chromosomes.

The enzyme is critical because of the way DNA is copied when cells divide. The device that copies the double-helix can't transcribe the last few units of DNA at the tip of the chromosome, so each time a cell divides, a little part of the chromosome is lost. The end section, known as a telomere, effectively serves as a molecular clock, ticking off units until it runs out, and the cell is incapable of dividing again.

Geron scientists inserted the telomerase gene into human cells, then sent a chemical signal that activated the cells. They found the cells began to build their telomeres back up, effectively rewinding the molecular clock to a more youthful state and creating many more chances to divide.

The scientists referred to the re-engineered cells as “rejuvenated.” But they noted that does not mean one will be able to rejuvenate human tissues. Rather it could lead to therapies that revive telomeres on specific cells -- perhaps growing new skin for burn victims or manufacturing blood vessels for elderly patients suffering from macular degeneration, a disease of the retina.

“If everything turns out to be safe and we can turn telomerase on in many different tissues, that might be where this research leads,” says Calvin Harley, Geron's vice president and chief scientific officer.

It's still unclear how the research will affect cancer treatment. Telomerase is dormant in most cells but is active in about 85 percent of cancer cells. Thomas Cech, a University of Colorado biochemist and 1989 Nobel laureate, speculates it may be possible to develop a drug to turn off telomerase production in cancer cells, causing them to revert to normal activity.

“Geron would have us believe that telomerase is the key to immortal life, and I have no idea if there is any wisp of truth in that,” says Robert Weinberg, an expert on cancer genetics at the Whitehead Institute in Boston.

The 'Gene Chip'

Besides manipulating genes in test tubes, researchers are blending semiconductor technology with biology to find quick, low-cost ways of exploring the variations in DNA.

Scientists at the Palo Alto, Calif., technology firm Affymetrix last year perfected a “gene chip” that is similar to the silicon wafers found in electronics but contains molecules of DNA instead of transistors. Researchers at pharmaceutical companies and universities use the chips to measure gene expression and detect mutations that may trigger dispositions to cancer, AIDS and other conditions. [30]

The dime-sized glass chips are encased in a small cartridge and contain molecules of DNA programmed for the sequence of whatever gene researchers want to target. The DNA chemically recognizes a real gene and can highlight the mutations it carries and offer clues about how well the gene is working.

The technology means a researcher can download the DNA sequence of an organism from a computer data bank, then have a programmer design a chip to study the activity of all of its genes. The genes to be tested are cut into fragments, tagged with a fluorescent chemical, then injected into the gene chip cartridge. By scanning with a laser, the researcher can see portions light up where the chip's DNA probes match fragments. The brightness indicates the order of DNA in the targeted gene.

The cutting-edge technology enables researchers to probe the mysteries of life without touching lab animals or human tissue. Many scientists rave about the process, saying it's faster and cheaper than creating mutant cells and subjecting them to a host of conditions, hoping for clues about its function.

“This technology is a rapid and accurate way of obtaining information about genomes,” says Joseph Hacia, a researcher at the National Human Genome Research Institute, who used the chips to detect sequences of primate genes. “You have to make a big investment to get [the initial] sequences, but then you can use that investment to get sequences of close relatives at a relatively cheap price.”

Hacia and his colleagues hope to compare chimpanzee and human genes, which only differ in about 1.5 percent of all DNA sequences. The differences may explain why humans have bigger brains and are capable of more complex thoughts.

Affymetrix expects to perfect a new chip that can monitor 50,000 human genes at once. Longer-term, the company is working under a $31-million grant with Stanford University and the U.S. Commerce Department to develop automated miniature genetic diagnostic systems that can be used in doctors' offices.

Enal Ravzi, biotechnology analyst for Frost & Sullivan, a market research firm in Mountain View, Calif., predicts that within five years, pending Food and Drug Administration approval, clinical diagnostics firms will routinely use the equipment to test for life-threatening conditions at a much lower cost than what is currently available on the market.

But the rapid developments concern many bioethicists, who predict insurance companies and employers also will quickly turn to the devices as a low-cost way to screen for high-risk applicants and prospective employees. They note the companies now are reluctant to use genetic tests because they are too expensive.

“This is a social disaster waiting to happen,” says Curtis Naser, a bioethics expert at Fairfield University in Connecticut. “We presently have little or no public policy to deal with these problems, yet the development of genetic testing proceeds apace. It would be naive to expect those contributing to the 'progress' of the human genome project . . . to slow down their efforts. There simply is too much money at stake.” [31]

Even scientists using the technology have concerns. Last year, a federal task force on genetic testing completed a two-year study concluding the rapid pace of test development, combined with the rush to market them, may create an environment in which genetic tests are available to health-care consumers before they have been adequately validated. [32]

Neil Holtzman, professor of pediatrics at Johns Hopkins Medical Institutions and chairman of the panel, says members were particularly concerned about tests predicting the risk of future disease in people who are currently healthy when no other tests are available to confirm the diagnosis. “We want to set up principles for the development of genetic tests, assure lab quality for these tests and see that [test-takers] are educated and counseled,” Holtzman says. “A lot of people are concerned about these issues.”

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Outlook

Race for the Cure

Now that researchers have spelled out large parts of the human genome and identified individual genes linked to many afflictions, they are rushing to develop a new generation of blockbuster drugs to treat diseases.

Pharmaceutical firms are scrambling to find biotechnology partners to underwrite the cost of developing new agents and sell them around the world. The big drug companies hope combining research and development will drive down the cost of bringing a drug to market, which industry analysts say can total $300 million or more.

Even government and university labs that once concerned themselves with fundamental questions such as how cells divide and how genes are regulated are trying to direct their research toward increasingly practical applications. “We're trying to translate more discoveries into actual treatments, and I think five years from now you'll see a lot of basic science turned into targeted therapies,” says Hyman at the National Institute of Mental Health.

“Most of the research focus has been on improving diagnoses and treating straightforward diseases,” says Greenberg of the National Institute of General Medical Science. “I think we're beginning to enter a new era that tries to get at the complexity of things, understand how genes interact with the environment and deal with the roots of common afflictions like high blood pressure and diabetes.”

The new drugs, called protease inhibitors, have proved to be effective in treating very ill AIDS patients, with few dangerous side effects. But large doses are required and the cost of the so-called “#########” can reach $20,000 a year, making them beyond the reach of all but the best-insured patients. The ideal remedy would be a vaccine that inoculates against HIV infection. But because the virus is so deadly, scientists can't inject a weakened virus for immunization, as they did for polio. [33]

Scientists like Greenberg and Hyman note that the social and economic costs of behavior fuel the quest for better remedies. Drug and alcohol addiction, which are both believed to be heritable, cost the United States billions of dollars each year in medical services and counseling and lower worker productivity. Similarly, learning disabilities are estimated to cost taxpayers $5.8 billion a year because of special education needs.

However, skeptics remain concerned that the push to develop wonder drugs for some conditions may raise public expectations to sometimes unreasonable levels. To many, the stimulant drug Ritalin illustrates the inherent dangers.

The drug is prescribed to children suffering from attention-deficit/hyperactivity disorder, or ADHD, which is sometimes associated with learning disabilities, delinquency, substance abuse and academic problems. Advocates say it efficiently pinpoints and stimulates the area of the brain that secretes chemicals that tell a person to pay attention to specific stimuli and ignore others.

But many have grown suspicious of the drug, saying it amounts to a quick fix but does not address underlying behavioral problems. Skepticism intensified after a recent surge in the number of children diagnosed with ADHD. Some estimates show as many as 5-6 percent of all school-age boys in the United States now take Ritalin for the condition. The United Nations International Narcotics Control Board has questioned whether the drug is being overprescribed. [34]

Biotech critic Rifkin says the rapid pace of research goes deeper than merely promising cures and revises fundamental notions of evolution. Gradually people perceive living things as bundles of information, without individual characteristics or souls, he says.

“All living beings are drained of their substance and turned into abstract messages,” Rifkin writes in his new book, The Biotech Century. “Life becomes a code to be deciphered. There is no longer any question of sacredness or specialness. How could there be when there are no longer any recognizable boundaries to respect? . . . Everything is pure activity, pure process.”

Rifkin sees a “bio-industrial world” emerging, in which animal and human cloning will become commonplace. And people will be able to obtain precise genetic readouts of themselves and offspring, even allowing them to make genetic changes to fetuses to correct diseases, enhance mood and change appearance and intelligence. “The biotech revolution will force each of us to put a mirror to our most deeply held values,” Rifkin writes.

Neuroscientist Evan Balaban hopes the hubub over genes determining complex behavior will slowly subside, to be replaced by a more empirical focus on the basic roots of human development. But he predicts society will continue to rely on science to provide easily digestible explanations.

“It's a particularly American thing to view the individual as somehow no longer responsible -- we look to explain away something as pathological,” Balaban says. “The focus isn't so much on the attribute as on how you got it. I find that curious.”

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Footnotes

[1] Quoted in Philip Cohen, “The Right Chemistry,” New Scientist, Dec. 13, 1997. Thomas is now at the University of Pennsylvania.

[2] For background, see “The Cloning Controversy,” The CQ Researcher, May 9, 1997, pp. 409-432.

[3] For background, see “Intelligence Testing,” The CQ Researcher, July 30, 1993, pp. 649-672.

[4] See Natalie Angier, “Grumpy, Fearful Neurotics Appear to Be Short on a Gene,” The New York Times, Nov. 19, 1996, p. A1. For background, see “Prozac Controversy,” The CQ Researcher, Aug. 19, 1994, pp. 721-744.

[5] See Curt Suplee, “Personality Type Tied to DNA Sequence,” The Washington Post, Jan. 2, 1996, p. A3.

[6] See Sharon, Begley, “Is Everybody Crazy?” Newsweek, Jan. 26, 1998, pp. 51-55.

[7] See Virginia Morell, “Evidence Found for a Possible 'Aggression Gene,'” Science, June 18, 1993, pp. 1722-1723.

[8] Quoted in Peter Maass, “Crime, Genetics Forum Erupts in Controversy,” The Washington Post, Sept. 24, 1995, p. B1.

[9] See “Behavioral Genetics '97: American Society of Human Genetics Statement: Past Accomplishments and Future Directions,” American Journal of Human Genetics, 60: pp. 1265-1275, 1997.

[10] See David L. Wheeler, “The Biology of Crime: Protesters disrupt meeting on possible genetic basis of criminal behavior,” The Chronicle of Higher Education, Oct. 6, 1995, p. A10.

[11] Wasserman's comments were included in a collection of perspectives on the conference that was published in Politics and the Life Sciences, March 1996, pp. 83-109.

[12] See Albert J. Reiss Jr., Klaus A. Miczek and Jeffrey A. Roth, eds., Understanding and Preventing Violence, Vol. 2, Biobehavioral Influences (1994). The National Research Council is the operating arm of the National Academy of Sciences and the National Academy of Engineering.

[13] Statement responding to critics, issued Nov. 4, 1996, from “Stalking the Wild Taboo” Web site, www.groupz.net-lrand/jpr01.html.

[14] See John Horgan, “Genes and Crime: A U.S. plan to reduce violence rekindles an old controversy,” Scientific American, February 1993, p. 24.

[15] See Thomas H. Maugh II, “Lead Exposure May Contribute to Crime,” Los Angeles Times, Feb. 7, 1996. For background, see “Lead Poisoning,” The CQ Researcher, June 19, 1992, pp. 525-548.

[16] Politics and Life Sciences, op. cit., p. 84.

[17] Ibid., p. 105.

[18] For background, see “Gene Therapy's Future,” The CQ Researcher, Dec. 8, 1995, pp. 1089-1112.

[19] See Carey Goldberg, “DNA Databanks Giving Police Powerful Weapon: The Instant Hit,” The New York Times, Feb. 19, 1998, p. A1. For background, see “Science in the Courtroom,” The CQ Researcher, Oct. 22, 1993, pp. 924-925.

[20] Quoted in Alberta Heritage Foundation for Medical Research Newsletter, March/April 1995. For background, see “Breast Cancer,” The CQ Researcher, June 27, 1997, pp. 553-576.

[21] See R. Grant Steen, DNA and Destiny: Nature and Nurture in Human Behavior (1996), pp. 273-274.

[22] Quoted in “Gore Urges Curbs on Genetic Testing,” The Associated Press, Jan. 21, 1998.

[23] See Dan Carney, “Senate Vote Blocks Debate On Bill To Ban Cloning,” CQ Weekly Report, Feb. 14, 1998, p. 395.

[24] Opinion piece, Roll Call Health Care Policy Briefing, Feb. 23, 1998, p. 14.

[25] See Arthur Allen, “The Mysteries of Twins,” The Washington Post Magazine, Jan. 11, 1998.

[26] See Thomas J. Bouchard, David T. Lykken, Matthew McGue, Nancy L. Segal and Auke Tellegen, “Minnesota Study of Twins Reared Apart,” Science, Oct. 12, 1990.

[27] See “Biology Isn't Destiny,” The Economist, Feb. 14, 1998, pp. 83-85.

[28] Quoted in “A New Five-Year Plan for the U.S. Human Genome Program,” National Human Genome Research Institute Web site, http://www.nhgri.nih.gov/HGP/HGP-goals/plan.html.

[29] See Nicholas Wade, “Cells' Life Stretched in Lab,” The New York Times, Jan. 14, 1998, p. A1.

[30] See Sandeep Junnarkar, '“GeneChip' Encodes DNA on Silicon,” The New York Times, March 15, 1997.

[31] From Loyola University, Chicago, Department of Mathematical and Computer Sciences, 1997 ethics papers. Available on the Web at www.math.luc.edu/ethics1997/papers/naser.html.

[32] National Institutes of Health and U.S. Department of Energy Task Force on Genetic Testing, October 1997.

[33] For background, see “Combating AIDS,” The CQ Researcher, April 21, 1995, pp. 345-368.

[34] See Kristin Leutwyler “Paying Attention,” Scientific American, August 1996. For background, see “Learning Disabilities,” The CQ Researcher, Dec. 10, 1993, pp. 1081-1104.

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Bibliography

Books

Ridley, Matt, The Origins of Virtue, Viking, 1996. A science writer and zoologist discusses the biological basis for human behavior and how the individual gene has replaced the species as the basic unit of evolution. He focuses on how social values can evolve when evolutionary biology teaches that people are driven by “selfish” genes.

Gallagher, Winifred, I.D.: How Heredity and Experience Make You Who You Are, Random House, 1996. A journalist examines the nature-nurture debate through a 40-year case study of a woman named Monica. Born with a serious birth defect and neglected by her mother, the child nonetheless had a cheerful disposition and was nurtured by the hospital staff. Her transformation into a happy productive wife and grandmother is intended to illustrate the argument that biology and environment work in tandem to influence behavior.

Peter Copeland, Living With Our Genes: Why They Matter More Than You Think, Doubleday, 1998. Hamer is the National Cancer Institute biologist who caused a stir when he claimed to have discovered a so-called “gay gene.” In this recently published book, he asserts that genes influence myriad human behaviors and conditions, including sex, anxiety and anger. The authors explain the biochemistry underlying the conditions and examine how much of it is under genetic control.

Charles Murray, The Bell Curve, Free Press, 1994. In this controversial book, the authors argue that IQ is substantially inherited and that efforts to help the poor are likely to fail because poverty is a function of inherited low intelligence.

Steen, Grant R., DNA and Destiny: Nature and Nurture in Human Behavior, Plenum, 1996. A researcher in brain physiology argues human behavior is roughly half the result of genes and half the result of the environment. He explores the interplay between the two forces by discussing possible genetic links to alcoholism, homosexuality and intelligence.

Articles

Begley, Sharon, “Is Everybody Crazy?” Newsweek, Jan. 26, 1998, pp. 51-55. This special report provides a cleverly written look at how researchers are providing biological explanations to previously unexplained behavioral quirks.

Allen, Arthur, “The Mysteries of Twins: Why Genes Aren't Everything,” The Washington Post Magazine, Jan. 11, 1998, pp. 6-11, 21-25. Behavioral studies on similarities between twins pose difficult questions about whether biology or environment play a bigger factor.

Wray, Herbert, “Politics of Biology: How the nature vs. nurture debate shapes public policy -- and our view of ourselves,” U.S. News & World Report, April 21, 1997, pp. 72-80. An overview of the uneasy questions posed by advances in development biology and the difficulties of establishing root causes of behavioral traits.

Garelik, Glenn, “Born Bad? New Research Points to a Biological Role in Criminality,” American Health, November 1993, pp. 66-71. An even-handed view of the growing body of research suggesting some people are biologically predisposed to violence.

Reports and Studies

Jeffrey A. Roth, Understanding and Preventing Violence, Vol. 2, Biobehavioral Influences, National Academy Press, 1994. A National Research Council overview of influences on violence concludes there is substantial evidence of genetic links to antisocial behavior. It concludes there are diverse and subtle biological influences that work in tandem with environmental factors.

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Next Step

The Gene Factor

Gould, Stephen Jay, “The Internal Brand of the Scarlet W,” Natural History, March 1998, pp. 22-25. Gould discusses the eugenics movement and its use in the early 20th century to identify those immigrants to the United States who were undesirable. He also considers the continuing desire of society to find genetic causes for every behavior or personality trait.

Kiernan, Vincent, “Genetic Mutation Tied to Mental Illnesses,” The Chronicle of Higher Education, Jan. 16, 1998, p. A18. Researchers say that a mutation in a single gene appears to predispose people to mental illnesses severe enough for hospitalization. The conclusion came after analyzing the DNA of 11 blood relatives of individuals previously diagnosed with mental illness.

Kong, Dolores, “Obesity Study Cites Nature and Nurture,” Boston Globe, Sept. 25, 1997, p. A20. Many surmise that children of obese parents are more likely to grow up overweight, but until this study, published this week in the New England Journal of Medicine, there had been no major research on how parents' weight affects their offspring's prospects. The study finds that chubby babies with obese parents have a 40 to 79 percent chance of becoming obese young adults, as much as 15 times the risk for plump babies with slim parents.

Maugh, Thomas H., II, “Scientists Identify Gene That May Raise Schizophrenia Risk,” Los Angeles Times, Oct. 31, 1997, p. A3. University of California-Irvine scientists have identified a gene they believe increases the risk of both schizophrenia and manic-depressive illness -- mental disorders that, combined, affect as many as 5 million Americans. Although the history of attempts to associate genes with mental illness is littered with claimed links that could not be verified, the new finding seems credible, some experts said. They noted that the mutated gene falls into the same class of mutations as recently discovered genes linked to Huntington's disease, fragile X syndrome and several other disorders of the brain.

Saltus, Richard, “British Scientists Hint at Genetic Link to Social Behavior,” Boston Globe, June 12, 1997, p. A5. British scientists say they have found evidence of a gene that makes girls superior to boys at winning friends and knowing how to behave in social situations. The research team, led by Dr. David H. Skuse, a child psychiatrist at University College, London, inferred the gene's existence by studying girls with a rare genetic disorder called Turner's syndrome.

Saltus, Richard, “Study Finds Gene Defect Can Cause Overeating,” Boston Globe, June 24, 1997, p. A3. Providing the first concrete proof that a genetic mutation alone -- not simply a lack of willpower -- can cause humans to overeat, scientists have discovered flawed genes that apparently caused massive obesity in two cousins and an unrelated woman.

Violence and Aggression

Brody, Jane E., “Genetic Ties May Be Factor in Violence in Stepfamilies,” The New York Times, Feb. 10, 1998, p. F1. Dr. Martin Daly and Dr. Margo Wilson, evolutionary psychologists at McMaster University in Hamilton, Ontario, found that the rate of infanticide was 60 times as high and sexual abuse was about eight times as high in stepfamilies as in biologically related families.

Maass, Peter, “Crime, Genetics Forum Erupts in Controversy,” The Washington Post, Sept. 24, 1995, p. B1. A University of Maryland conference on links between genes and criminal behavior is facing criticism, with protesters saying scientists are trying to find a gene that links minority groups, especially African Americans, to violent behavior.

Rose, Steven, “A Pizza Killer's Defense: Steven Rose Thinks That Genetic Science May Be Used to Try and Explain Away the Causes of Crime and Violence,” The Guardian, Jan. 22, 1998, p. 19. The author discusses whether all human activities can be blamed on genes. Using genes as an explanation for violent, criminal or socially deviant activities is simplification, he says, and fallacious.

Roush, Wade, “Conflict Marks Crime Conference,” Science, Sept. 29, 1995, p. 232. Charges of racism and eugenics exploded at a controversial University of Maryland meeting exploring the genetic basis of crime. Common ground found by the conference participants is discussed.

'Gay Gene' Controversy

Gallagher, John, “Gay for the Thrill of It,” Advocate: The National Gay & Lesbian Magazine, Feb. 17, 1998, p. 32-39. Geneticist Dean Hamer has written a new book entitled Living With Our Genes: Why They Matter More Than You Think. Hamer doesn't think there is a “gay gene,” but rather a variety of genetic markers that shape a person's tendency to be gay or straight. Brief excerpts from the book are offered.

Pool, Robert, “Portrait of a Gene Guy,” Discover, October 1997, p. 50-55. Part molecular biologist and part psychologist, Dean Hamer is one of a small but growing group of researchers who look for the genes that shape our individual personalities. Hamer, who believes that something important about human behavior can be learned by studying its genetic basis, is profiled.

William Byne;, “The Ethics of Genetic Research on Sexual Orientation,” Hastings Center Report, July 1997, pp. 6-13. Research into sexual orientation provokes intense controversy for a number of reasons. The very motivation for seeking an “origin” of homosexuality reveals homophobia, the authors maintain, and such research may lead to prenatal tests that claim to predict homosexuality.

Human Genome Project

Allen, William, “Scientists See Perils in Unraveling the Mysteries of Human Genetics,” St. Louis Post-Dispatch, Feb. 15, 1998, p. A16. The hype surrounding the Human Genome Project could lead to the return of an abusive social movement known as eugenics, warns Garland Allen, a Washington University historian. Allen traced the links between the genome project and the eugenics movement of the early 20th century in a lecture during the annual meeting of the American Association for the Advancement of Science in Philadelphia.

Saltus, Richard, “Top Scientist Urges Shortcut on Gene-Mapping Research,” Boston Globe, Sept. 7, 1997, p. A8. The government's top genetic scientist is calling for an urgent shortcut in the human genome project, saying researchers should quickly hunt down common genetic differences that make some people more susceptible to diseases rather than continuing to decipher genes randomly. If the genome scientists don't change course and hone in on the variations, private biotech companies may locate and patent the disease-related sequences, potentially inhibiting research, Dr. Francis S. Collins warned at a medical symposium last week.

Lab Mice

Mihill, Chris, “Scientists Breed Mice With Full Human Chromosomes,” The Guardian, June 4, 1997, p. 12. Scientists are today claiming a new milestone in genetic engineering with the transfer to mice of entire human chromosomes -- long strands of DNA containing thousands of genes -- rather than just the implantation of single genes. For years it has been possible to insert isolated human genes into mice and other animals.

Petit, Charles, “Firefly Genes Light Up Stanford Research Mice,” San Francisco Chronicle, Oct. 11, 1997, p. A1. Scientists at Stanford University are using mice and rats that glow faintly in the dark -- thanks to firefly genes inserted into their cells -- as potent new tools for medical science. By using genes that give cells the power to glow, researchers can more easily tell whether transplanted DNA is functioning in living cells selected for therapy or study.

Trafford, Abigail, “A World of Research on the Shoulders of a Mouse,” The Washington Post, July 29, 1997, p. WH6. Mickey and Minnie would be stunned by all the new members of the mouse family: inbred mice, hybrid mice, mice made to carry human genes, mice with a particular gene deleted -- the so-called knockout mouse -- so that scientists can see what that gene really does. The mouse is also a living test tube for new drugs.

Genetic Discrimination

Armour, Stephanie, “Workers Fear Genetic Discrimination,” USA Today, Feb. 25, 1998, p. B4. The surge in genetic research has employees worried bosses will use DNA tests in hiring and firing. Research advances are making it possible to identify a host of health risks related to genetic traits. Just this month, a federal appeals court ruled secret testing of employees is unconstitutional. The ruling stemmed from a lawsuit by workers who say Lawrence Berkeley National Laboratory covertly tested them for syphilis, pregnancy and the sickle-cell trait. The action sends the lawsuit to a lower court for trial.

Page, Susan, “White House: Ban Gene Bias in Workplace,” USA Today, Jan. 20, 1998, p. A1. The White House today will endorse a federal ban on discrimination against workers in hiring or promotion because of their genetic makeup. “In the next five to 10 years, there will be tens if not hundreds of genetic predisposition tests available,” says Francis Collins, director of the Human Genome Project, a federal research effort to map human DNA. “If no protections are in place, it could be used to deny us a job, and that seems patently unfair. One thing you don't have much choice about is your DNA sequence.”

“The New Discrimination,” Los Angeles Times, July 20, 1997, p. M4. Simple blood tests have been developed in recent years that use genetic markers to identify hereditary leanings toward certain diseases. The tests give valuable early warnings but also are a potential source of discrimination, providing reasons for denial of employment or insurance coverage. Proposed federal legislation would go far toward blocking that threat. While new genetic tests are swiftly coming on the market, however, studies show that many Americans avoid them out of a justified fear of discrimination.

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Contacts

National Human Genome Research Institute

National Research Council
2101 Constitution Ave., N.W., Washington, D.C. 20418
(202) 334-2000
http://www.nas.edu
Part of the National Academy of Sciences, the council advises the nation's leaders on scientific issues that pervade policy decisions, including the ramifications of linking genetics to behavior.

Foundation on Economic Trends
1660 L St., N.W., Washington, D.C. 20036
(202) 466-2823
Headed by Jeremy Rifkin, the foundation examines the environmental, economic and social consequences of genetic research and pursues public-policy initiatives.

Biotechnology Industry Organization
1625 K St., N.W., Suite 1100, Washington, D.C. 20006
(202) 857-0244
Representing more than 500 biotech companies, this trade association monitors government activities at all levels, promotes educational activities and organizes workshops.

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Special Focus

No Mickey Mouse Research for these Rodents, Mice are the Test Animals of Choice

Is Sexual Orientation Genetically Determined? Researchers Are Looking for a 'Gay Gene'

Genome Project Makes Progress

They're cheap, easy to breed and have genes that can be easily manipulated at the molecular level. Is it any wonder laboratory mice have become the test animals of choice in the current explosion of genetic research?

Over the last decade, researchers have used millions of the rodents to study the detailed function of individual genes. Because scientists can pinpoint the DNA code of many genes -- and because researchers have a complete genetic map of the mouse -- they are able to chemically alter the code and inactivate, or “knockout,” specific genes in the rodents. The resulting “knockout” mice are providing important clues about the development of cancer, sickle-cell anemia and myriad other conditions.


Lab mice have played a critical role in recent genetic discoveries. (Photo Credit: Tom Levy)

In addition to switching genes on and off, scientists are cloning genes from other animals and introducing them in mice. The mice then transmit the genes to offspring. Because mouse and human genomes are similar, these “transgenic” rodents provide useful models of human tendencies to certain conditions. [1]

Mice have gradually replaced primates, cats and dogs as the pre-eminent test animals in university, government and corporate labs. Part of this is due to practical considerations -- a typical lab mouse costs between $2 and $2.50 and can produce offspring in three weeks. Also, public sympathy tends to be lower for rodents than for cats, dogs or monkeys, reducing the likelihood of emotional protests against animal research. [2]

One important use of transgenic mice is in cancer research. Researchers have found cancer is partly caused by damage to genes that regulate cell growth. Harvard University geneticist Philip Leder introduced active damaged genes, called oncogenes, into special strains of mice, then watched them pass on the genes to offspring. The results indicate that conditions such as leukemia and lymphoma are often caused by two or more oncogenes, meaning cancer likely requires several activating events.

“Our work has been considerably advanced by introducing active oncogenes into the hereditary makeup of special strains of lab mice,” Leder says. “In many ways, [the] mice become useful models of human malignancy.” [3]

Last year, researchers at the University of Alabama at Birmingham, Lawrence Berkeley National Laboratory and the University of California at Berkeley used knockout mice to develop the first animal model for sickle-cell disease. The scientists successfully transplanted human genes with defective hemoglobin into the rodents, capping a long-running research effort. [4]

“This is a major advancement a lot of labs have been trying to achieve for more than a decade,” says Alan Schechter, a sickle-cell expert at the National Institutes of Health. “It's probably as good a mouse model as you could ever have for sickle-cell disease.”

Knockout mice also provide insights into behavior and the nature-nurture debate. Researchers at the National Human Genome Research Institute last year reported using knockouts to isolate what they termed the first gene affecting social behavior in mammals. The gene was the mouse version of the so-called “disheveled” gene, first found in fruit flies, that controls cell-to-cell signal pathways. [5]

Mice that had the gene inactivated appeared to have normal learning and memory patterns. But they consistently exhibited odd anti-social behavior, interacting less, failing to fluff up suitable beds for nesting material and, most notably, not engaging in a characteristic pattern of trimming each other's whiskers. Researchers hope finding a genetic link will provide clues about the development of autism, schizophrenia and Tourette's syndrome in humans.

Designing the mice has become something of a specialty. The Jackson Laboratory, founded in 1929 in Bar Harbor, Maine, is among the largest suppliers, shipping 2 million mice a year from more than 1,700 stocks and strains. The lab has the world's largest frozen mouse embryo repository so particular genetic strains can be thawed and carried to full term with no damage in foster mothers.

But animal-rights groups, while praising legitimate scientific findings, say the genetic tinkering has many unintended consequences. Some transgenic mice bred to develop eye tumors also suffered cancer throughout their bodies. There are other published examples of animals being born with loss of limbs, facial clefts and massive brain defects.

Animal Aid, the largest British animal rights group, urges scientists to do more work on human cells in test tubes, noting some diseases like cystic fibrosis are expressed differently in mice and men. The group advocates removing human cells from patients, incorporating healthy genes into the cells in a test tube, then returning them to the patient.

“Ultimately, it is clinical, patient-oriented studies that give the most valid results,” the group says.

 

[1] See Holly Ahern, “It's A Knockout: Mice Advancing Research as Lab Animals of Choice,” The Scientist, Vol. 9 No. 14, July 10, 1995, p. 18.

 

[2] For background, see “Fighting Over Animal Rights,” The CQ Researcher, Aug. 2, 1996, pp. 673-696.

 

[3] Quoted in Howard Hughes Medical Institute, 1995 Annual Report, Biomedical Research, p. 53.

 

[4] See Warren Leary, “Gene-Altered Mice Are Called First True Sickle Cell Model,” The New York Times, Oct. 31, 1997, p. A20.

 

[5] See Nicholas Wade, “First Gene for Social Behavior Identified in Whiskery Mice,” The New York Times, Sept. 9, 1997, p. C4.

Much of the conflict between homosexual activists and their foes springs from disagreements over the nature of homosexuality. Most gays and lesbians contend their sexual orientation is either an inborn trait or an immutable and healthy psychological condition developed in the early years of life. In contrast, opponents of gay rights insist homosexuality is a consciously acquired mode of behavior that can be changed or acquired at will.

The debate over the basis of homosexuality took a new turn in 1993, when National Cancer Institute scientist Dean Hamer reported in the journal Science that he had linked male homosexuality to a small region of one human chromosome. Hamer emphasized that he had not isolated a single gene, and had no way of knowing how the DNA in question contributes to sexual orientation or how often people were likely to become gay as a result of carrying it. [1]“”

Hamer's work was built around a study of 40 pairs of gay brothers. In 33 of the pairs, the brothers were found to have identical pieces of the end of the sausage-shaped X chromosome. Normally, only half of the pairs of brothers should have shared the common region. The odds of Hamer's results turning up randomly were less than half a percent.

The timing was dramatic, coming as the nation was in the midst of a debate over gay rights in the military. In addition, several states were considering measures barring laws that protect gays and lesbians from discrimination. Legal experts speculated that if homosexuality could be demonstrated to be inborn, discriminatory laws against gays and lesbians would probably be invalidated by courts. [2]

Yet in succeeding years Hamer's results were never duplicated. Moreover, his work was investigated by the Office of Research Integrity, a branch of the U.S. Public Health Service, after a colleague accused him of cooking the results. Hamer eventually moved on to other research, including studying whether there is a gene for nicotine addiction.

“I'm convinced that in the end the positives [of linking genes to behavior] will outweigh the negatives,” he says. “We'll learn more about ourselves and others. Understanding your genetic makeup is the key to figuring out who you are. This is a tool for liberation, a scientific window into the soul.” [3]

Hamer's work has sparked intense criticism and division in the scientific and gay-rights communities. Some homosexual leaders fear that any legitimate link between genes and sexuality will spark calls for therapy to correct the condition. Indeed, the Rev. Louis Sheldon, president of the Traditional Values Coalition in Anaheim, Calif., has asserted that if the findings are confirmed, society should develop gene therapy “to correct that genetic defect.” [4]

Conservative groups, who tend to depict homosexuality as a behavioral choice, also have attacked the research, citing it as an example of how federal funding is being used to advance gay political activism. Hamer's work is part of the Clinton administration “methodically unleashing an avalanche of pro-homosexual policies and advocacy,” according to Robert Maginnis, policy analyst for the Family Research Council. [5]

But others see positive results from such work. Simon LeVay, a former Harvard University researcher and founder of the Institute of Gay and Lesbian Studies in West Hollywood, Calif., says the perception that gays are a distinct biological group, rather than heterosexuals behaving inappropriately, helps the gay political agenda.

LeVay points to polls showing people who think homosexuality is a choice are more likely to be homophobic. One such poll taken last year for U.S. News & World Report found that while only 45 percent of 1,000 adults surveyed favor gay rights, 69 percent of those who believe homosexuality is completely or mostly controlled by heredity and genes favor gay rights.

“We think it's important there be sound scientific research into sexuality,” says Kim Mills, director of education for the Human Rights Campaign, a Washington-based gay-rights group. “While the basic issue is equal rights for us, it's important that the public understand whatever the basis is for sexual orientation.”

Many still believe there is some genetic component to gayness, though the connections -- like so many others between biology and behavior -- are murky at best.

“There is a consensus that none of the possible factors for establishing orientation are ones ordinarily considered to be under an individual's control,” says Georgetown University Law Center Professor Chai Feldblum. “Sexual orientation is not a characteristic which an individual can be said to easily change through simple choice.” [6]

Researchers continue to explore the subject. LeVay has concluded that the hypothalamus, a region of the brain that controls hormonal functions, is much larger in straight men than in gay men or in women.

A team at the University of Texas at Austin reported in March that, compared with heterosexual women, the hearing of homosexual and bisexual women tends to be more like that of men. The findings suggest that homosexual and bisexual women develop in slightly different ways than heterosexual women, and that their brains may also form differently, accounting for their sexuality. [7]

“It's an indication that other brain sites have also been masculinized,” says Dennis McFadden, a professor of experimental psychology at the University of Texas who led the study. He says he and his colleagues are doing follow-up research to see if they can identify specific differences in the brains between heterosexual, homosexual and bisexual women. [8]

 

[1] See Natalie Angier, “Report Suggests Homosexuality is Linked to Genes,” The New York Times, July 16, 1993, p. A1.

 

[2] For background, see “Gay Rights,” The CQ Researcher, March 5, 1993, pp. 193-216. and “New Military Culture,” The CQ Researcher, April 26, 1996, pp. 361-384.

 

[3] Quoted in Robert Pool, “Portrait of a Gene Guy,” Discover, October 1997.

 

[4] Quoted in Larry Thompson, “A Search for a Gay Gene,” Science, June 12, 1995.

 

[5] Robert Maginnis, “Insight: Federal Government Promotes Homosexuality Using 'Diversity' Cover,” Family Research Council, December 1994.

 

[6] Testimony before the House Small Business Subcommittee on Government Programs and Oversight, July 17, 1996.

 

[7] See Rob Stein, “Study Suggests Biological Basis for Lesbianism,” The Washington Post, March 3, 1998, p. A9.

 

[8] Ibid.

February 1998: Researchers at the National Institutes of Health (NIH) and Johns Hopkins School of Medicine demonstrate for the first time in a non-human primate that gene therapy works against viruses that destroy the immune system. The work may eventually benefit patients infected with HIV, the virus that causes AIDS.

January 1998: NIH researchers find a mutated gene that causes Hirschsprung's disease in lab mice. The rare genetic malady leaves the colon with no nerve cells, meaning it can't relax. Scientists are looking for the equivalent mutated gene in humans.

November 1996: Teams at NIH, Johns Hopkins and the University of Umea in Sweden identify the location of the first major gene that predisposes men to prostate cancer. The so-called HPC-1 gene is situated on the long arm of chromosome 1.

November 1996: For the first time, scientists pinpoint the location of a gene they believe is responsible for some cases of Parkinson's disease, a degenerative neurological disorder. They hope to learn why nerve cells die in Parkinson's and how to stop them from dying.

October 1996: A team of 100 scientists from government, university and commercial labs reveal a map that details the locations of more than 16,000 genes in human DNA -- about one-fifth of the total DNA packaged in human chromosomes. The results mean the number of mapped human genes has tripled in less than two years.

April 1996: An international consortium finishes spelling out the entire genetic code of a common species of yeast, among the most advanced organisms to be entirely sequenced. Sequences in the 12,057,500 chemical subunits of its nuclear DNA will help researchers understand the function of individual human genes in medical problems.

March 1996: The Human Genome Project completes a five-year effort to develop a genetic map of DNA from a common lab mouse. The mouse's genetic information is about 75 percent similar to a human's. Spelling out the entire sequence takes 500 journal pages.

October 1995: Results from the first human gene therapy trial show success treating two girls with adenosine deaminase deficiency, a very rare form of immunodeficiency disease. Both received copies of a replacement gene that codes for the enzyme ADA.

June 1995: A gene is isolated for the childhood disease ataxia-telangiectasia, a rare hereditary neurological disorder. Researchers believe it could provide a marker for predisposition to certain cancers and people sensitive to radiation.

 

[1] For background, see “Gene Therapy,” The CQ Researcher, Oct. 18, 1991, pp. 777-800, and “Gene Therapy's Future,” The CQ Researcher, Dec. 8, 1995, pp. 1089-1112.