Nature or Nurture

Perfect Pitch

A musical tone is defined by the speed with which a vibrating instrument generates a sound wave. When an orchestra tunes, the players key to the first violin's A, which propagates across the stage at 440 cycles per second. When Dr. Joseph Profita, a psychiatrist who works at the Veterans Administration Hospital in Sepulveda, California, hears a tone, he instantly recognizes it. He and about 1 in 2000 other people, including Nat King Cole, Andre Previn, and about 10% of the students at the Juilliard School of Music, were born with the capacity for perfect pitch. With appropriate early training, they hear notes as easily as you see colors. Just as you know instantly and unequivocally when you see green or purple, people with perfect pitch immediately recognize an F or a G. Dr. Profita realized that he could identify tones long before he understood anything about music.

Perfect pitch is neither necessary nor sufficient for a successful music career, but it is clearly of great value to a professional musician. Yet, despite how proficient pianists or violinists might be at their instruments, if they were not born with perfect pitch, they cannot develop it. They can with effort teach themselves to have perfect relative pitch—the ability to recognize a second tone from a reference note—but they must always have the anchor. To envious fellow musicians, their colleagues with perfect pitch must seem to come and go freely in a tonal space that they cannot enter.

Dr. Profita, who is a fine amateur pianist, has also become an amateur geneticist. For many years he has sought out other people with perfect pitch and asked whether it was shared by any of their relatives. As the anecdotal evidence that this was a heritable trait mounted, he became more interested in testing that hypothesis. He realized that he could not do so until he had a way to assess the presence or absence of perfect pitch in people who had no special interest in music. Because most people with perfect pitch are not professional musicians, to pursue the question of heritability only among musical families would severely bias the investigation. Some years ago, he and several colleagues developed a test for perfect pitch that one can administer to persons even if they cannot read music or play an instrument. By the late 1980s, he had identified 60 families in which some members had perfect pitch. From analyzing the family trees, he showed that the data on who did or did not have perfect pitch were strongly consistent with (but did not prove) the presence of a highly penetrant autosomal dominant gene. In a nutshell, about one-half of the children of persons with perfect pitch also have the trait.

In 1997 a scientific team led by Nelson Freimer at the University of California in San Francisco took research on the origins of perfect pitch to a new level. Working with Shai Shaham, a gifted musician turned geneticist, and Siamak Baharloo, he and others developed a survey instrument with which to screen individuals to ascertain the likelihood that they have perfect pitch. Shaham, incidentally, is the brother of world-renowned violinist, Gil Shaham, and of the talented concert pianist, Orli Shaham. All three children and their father have perfect pitch. Among more than 600 professional musicians, the researchers found that about 15% have perfect pitch. Interestingly, virtually all of them who do started formal music training before the age of six. This suggests that the capacity for perfect pitch can be lost if not nurtured. The research team is among the first to recruit subjects over the Internet. They are trying to recruit 100 extended families with multiple members who have perfect pitch. They hope to collect DNA from all of them and within each family compare the DNA markers among those who have the trait to those who do not have it.

What is it like to have perfect pitch? Many musicians who have been interviewed say that they recognized and had distinct feelings about notes when they were as young as three. Some experience synesthesia; they associate certain notes with definite hues such as soft rose with a D and sharp yellow with an F. The associations differ with each person. Does perfect pitch make one a better musician? Opinions vary. Some musicians wryly insist that it merely makes one much more aware of one's mistakes.

Research into the genetics of perfect pitch is unlikely to be well funded, but we will find the relevant gene soon enough. By 2002 the consensus sequence—each of the 3,000,000,000 or more DNA letters code for all the genes in the human genome—will be literally available to everyone. It will be public information, any part of which can be accessed through a National Institutes of Health website.

Many environmental factors influence the role of music in one's life, and most persons with perfect pitch are not musicians. To those who may have little or no interest in music, this "talent" could be unimportant or even a hindrance. What most of us tolerate as the dissonance of everyday life (car horns, subway wheels, pots clanging) must be particularly irritating when the deviant notes are so obvious. They might take issue with my suggestion that perfect pitch is an example of a talent (defined in my tattered Webster's as a "natural endowment"). Still, I think it a fair example of a trait that some of us (my tone-deaf self included) would love to have, but realize is forever out of reach.

Galton's Legacy

Talent is ineffable and elusive. Although there is a good chance that no two people will agree on what it is or who has it and who does not, or who among people with particular talents is more talented, achieving rough consensus about who occupies the upper reaches in some firmament is not too hard. Michael Jordan, Tiger Woods, Stefi Graf, Leontyne Price, Seiji Ozawa, and Yo-Yo Ma have each reached greatness in his or her field. How did they do it? What is the nature of the complex interaction of genes with environment that has propelled them to such heights? What, if anything, can we say about their genes? We really have no idea what it is that enables a person to do so extraordinarily well at some endeavor that he or she escapes from the crowd of the very good to join the inner circle of the great. Even though there have been extraordinary advances in human genetics, we are not remotely close to being able to address questions such as what role a composer's particular genetic profile played in contributing to his or her success.

Efforts to parse the hereditary contribution to talent, or at least to attainments readily acknowledged and admired by others, began with a serious misstep. Francis Galton, a Victorian polymath and a cousin of Charles Darwin, was among the first to study the relationship between natural endowments and success in life. In 1865 he published two articles in MacMillan's magazine on the accomplishments of relatives of then-

prominent English judges during the prior two centuries. He reported that an impressive number of relatives had also achieved eminence and posited that they were members of what today we might call a genetic elite. In 1869 he published a book, Hereditary Genius, with the highly presumptuous subtitle, "An Inquiry into its Laws and Consequences." For each field in which he was interested—the work of judges, statesmen, military leaders, writers, scientists, musicians, painters, clergy, oarsmen, and wrestlers— Galton identified those men in England whom he thought most eminent. He then investigated whether or not they had eminent relatives and, if so, whether the number was much in excess of that which would be attributed to chance. In all the fields he investigated, Galton found substantial evidence that achievement was strongly influenced by heredity.

By today's research standards, his work is badly flawed. He barely considered, indeed virtually dismissed, the contribution of wealth, schooling, and social class to success in life. In 19th century England there were few paths to success for even the most talented person born into the poverty in which the mass of people lived. But, in providing what passed as scientific proof that inborn talents had allowed individuals to emerge over time as founders of family dynasties that continued through the generations to dominate English politics, arts, and science, Galton wrote for receptive readers. No one criticized him for failing to acknowledge that social class locked talented people out of the niches in which their abilities might flourish. A social Darwinian, Galton coldly argued that if a person had talent worth worrying about, that individual would break through to success.

Although Galton is correctly credited with being the founder of the eugenics movement (see Chapter 24), for most of the period when it flourished (about 1900-1940), the major focus was on preventing the flow of "defective" genes, not encouraging the flow of "positive" genes. Galton and his English disciples were among the few who instead sought to encourage the scions of talented families to pick talented spouses. In the United States, Teddy Roosevelt was among those ardent positive eugenicists who boldly urged healthy, intelligent young Americans to marry and have big families, the best antidote, they thought, to the polluting of the American "gene pool" caused by immigrants from southern and eastern Europe. Roosevelt's exhortations presaged by four decades the corrupt Nazi version of his vision known as Lebensborn, a determined effort to match young persons of good Teutonic stock to become parents for the fatherland.

Famous Families

When we consider the extraordinary accomplishments of groups of persons in particular families, the possibility that genes are a driving force in talent is not easy to dismiss. Who does not know that several of the greatest composers were raised by parents who were accomplished musicians? The Bach family includes at least 20 musicians across four generations who demonstrated special talent. Other great composers evidenced striking talent at such precocious ages that it is hard to imagine it as a product of great teaching. Mozart, Beethoven, Mendelssohn, and Schubert were publishing scores as children or young adolescents. In painting, Ruysdael and Titian (to name just two of many) were born into families of artists and both showed exceptional talent in childhood. Such family histories stimulated Charles Davenport, one of the founders of human genetics in the United States, to speculate naively that great artistic talent arose in children only if they inherited a pair of predisposing recessive genes!

By today's standards, Galton's research methods would fail peer review, but he still casts a long shadow. Throughout the 20th century, our culture has continued to be fascinated by families in which extraordinary talent, abilities not easily attributable solely to economic security or social class, persists through the generations. Consider, for example, an article in the New York Times Magazine entitled, "Natasha Richardson and the Redgrave Dynasty." The author began his story on the dynamic young actress, the fourth generation in the family to win fame on stage, in this way: "Her mother's daughter, her aunt's niece, her grandfather's granddaughter, her sister's sister—the career of the Americanized actress invites the intriguing question: Is talent hereditary?"

Natasha Richardson is the daughter of Vanessa Redgrave who vaulted to fame in 1967 with her performance in the film Blow Up. Vanessa is the daughter of Rachel Kempson and Sir Michael Redgrave, both acclaimed British actors. On the evening when Vanessa was born in 1937, Sir Michael was playing Laertes in Hamlet. Lawrence Olivier, who was playing the title role, stepped to the footlights and announced her birth to the audience, predicting that she would be a great actress—which she became. Vanessa's daughter, Natasha, appeared in her first film at age 4, and by 18 she was acting in London's West End. The author describes her as having "the family aptitude for emotional extremity." Elsewhere he says, "She has inherited her mother's smoky voice and her genius for emotional revelation, yet she is determined to make her career independently."

Which is it—heredity or environment? Natasha grew up in a wealthy household that was at the epicenter of theatrical life in England. As the author put it, she "inevitably attended drama school" and was pushed into theater work while still a young child. Throughout her childhood she watched her grandparents and mother win acclaim on stage. Although she is no doubt hurt by allegations of nepotism, Natasha Richardson would also have to acknowledge that many more theater doors were open to her than to her unknown competitors. The answer, of course, to the question is "both." Natasha may well have inherited vast complexes of as-yet-undescribed genes that fashioned her voice or cheekbones in ways that recall her mother's. On the other hand, if her mother had rejected the theater and made every effort to suppress an urge to act in her daughter, Natasha might well have grown up to be a lawyer or a teacher.

In 1997, four years after running the article on the Redgrave family, the New York Times again took up the heritability of talent in a piece entitled, "When Creativity Runs In the Family." The journalist, Loch Adamson, opened: "Artists may well be born, but they are also made." He opined, "it is tempting to ascribe artistic talent, even creativity, to genetic or neurological factors. Yet, even art and creativity are products of nature. They must all be nurtured, recognized, and supported." The article reviewed the impact upon talented children—Julian Fleisher, a jazz singer; Betye and Lezley Saar, visual artists; and Hallie Foote, an actress—of growing up under the influence of an extremely gifted and successful parent. Each child wound up working in the same artistic field as the parent, but all noted that observing the creative struggles (and, sometime, the despair) of their parents had at times dissuaded them from the road they ultimately decided to travel. Articles like this fail to do the obvious, which is to remind us of the far greater numbers of families in which a child does not follow a parent into artistic greatness. It seems to me that Ruth Richards, a psychiatrist at the Saybrook Institute in San Francisco, who was interviewed for the article, got it just right. "With the right combination of elements—

psychological, social, and biological—running in families, there is a real possibility of sparking eminent creativity."

Richards reminds us to avoid genetic reductionism (the notion that a person's destiny is encoded in his or her DNA). The shameful history of the eugenics movement (Chapter 24) proves that genetic reductionism flourished for a good chunk of the 20th century. It is, thus, difficult to dismiss concerns that it could rise again. During the 1990s, genetic imagery became a favorite of the advertising world and insinuated itself into every corner of modern life. Among the many early favorites I collected is a two-page glossy ad for the British Sterling automobile that graced the inside cover of Sports Illustrated in 1990 under the lead, "The remarkable handling of a Sterling. It's in our genes." Beneath, a beautiful photo of the automobile parked majestically before a brick mansion ran the explanation for its quiet, comfortable ride. "It's British. Nobody understands suspension quite like we do."

Intelligence

For most of this century, the center of the controversy over the genetic contribution to talent has been the debate over the heritability of intelligence. Argument perennially swirls around three issues. Can intelligence be defined? Can it be measured? To what extent is the capacity for intelligent behavior inherited? In 1906 the psychologist Henry Herbert Goddard imported the IQ test from France, where it had been developed by Alfred Binet and Theodore Simon as part of their struggle to determine the learning capacity of children with mental retardation. The test was quickly adopted by American psychologists. Just a few years later, government officials decided to administer it to every man who enlisted in the U.S. military. For most of the 20th century, taking an IQ test was almost a rite of passage for American children. Only recently has its validity been sufficiently challenged to cause doubts as to its value in guiding educational choices for children.

Is there a readily measurable human trait that is positively associated with achieving economic and social success in adult life and that is far more influenced by genes than environment? Unquestionably. It is height. Many studies have shown that most of the variance in adult height is attributable to genes. A number of impressive efforts compared final adult height among identical twins reared apart with that of identical twins, nonidentical twins, and siblings reared together. For example, in their 1937 book, Twins: A Study of Heredity and Environment, Newman, Freeman, and Holzinger, three scientists at the University of Chicago, studied height in 50 pairs of identical and nonidentical twins reared together, 52 pairs of siblings reared together, and 19 pairs of identical twins reared apart. More than 70% of the identical twin pairs, whether reared together or apart, had a final adult height that differed by less than 1.9 centimeters (three-quarters of an inch), whereas only 30% of nonidentical twins and sib pairs reared together (that is, in the same general environment) were so similar. The correlation coefficients for height between pairs of identical twins reared together or apart were much higher (greater than 0.9 where 1.0 would indicate that there was no discernible evidence of any environmental influence) than for nonidentical twins and sibs born at different times, suggesting that environmental factors played only a small role. Across all groups, the correlation coefficients were strongly positive, suggesting a major role for genes in determining height.

More than a few studies show that tall people are more likely to achieve economic and political success in American culture than are short people. Who does not know the trivial fact that all but a few American presidents have been significantly above average height? Although those of us, like myself, who are on the short side might not like to hear this, it is true. However, I suspect that few comparatively short people (those within 1-2 standard deviations from the mean) lose any sleep over their height after adolescence. This is not so much because they know that they can't change their height as because they realize that such a statistic has no predictive value for any one individual. Put another way, they know that there is substantial scatter in the correlation between height and success. Many short people do much better in life than do many tall people. Whatever the height advantage is, in the grand scheme of things, it is relatively small.

Whether intelligence, like height, is easily measured, highly heritable, and significantly correlated with socioeconomic success has been frequently and bitterly debated. During the 1920s, 1930s, and 1940s, due mainly to the influence of several large longitudinal studies, especially that of 1500 gifted (all but a few of whom had an IQ above 140) children in California by Stanford psychologist Lewis Terman, the dominant view embraced by American academia was that intelligence is measurable and cor relates well with later success. Terman did not focus on heritability, but he was struck by the observation that siblings of his gifted children (who were nicknamed "Termites") were also often gifted. During the early 1930s, Terman was convinced that the persistent differences among racial groups in mean IQ score could not be accounted for by environmental differences and, thus, must have a genetic basis, but as time went by, he backed away from this view.

Although children who take an IQ test several times over several years tend to receive quite similar scores, and although there is much evidence to confirm Terman's observation that persons who score high tend to enjoy socioeconomic success later in life, for the last 40 years there has been intractable debate as to what the test really measures and as to whether it is culturally biased. Some fascinating aspects of this debate are succinctly told by Stephen Jay Gould in The Mismeasure of Man, which won the award from the National Book Critics Circle for the best nonfiction book published in 1981.

Since the late 1960s, the influence and use of IQ testing in American society has been waning, in part because of accusations that it is biased in favor of white middle class children. One of the major inflection points in this trend occurred in 1968 when Arthur Jensen, an educational psychologist at Berkeley, reported that early intervention programs intended to help disadvantaged, predominantly black, youth were not providing any discernible impact on school performance. He argued that the 15-point difference in mean IQ scores between whites and blacks reflected an underlying biology that special educational efforts could not overcome. A few prominent psychologists, such as Hans Eysenck in Britain, supported Jensen, but the vast majority of educators rejected his work. Appearing at the zenith of our society's interest in affirmative action programs, his arguments also drew a fusillade of angry responses from less well informed critics.

Decades of research have consistently showed that as a group, African-Americans on average score consistently lower than, and Asian-Americans consistently score higher than, do whites. Of course, this is merely a summary statement about the results of testing in large populations that when compared show a huge overlap of test scores. Within these groups there are many black children who score higher than do many white children. Statistical observations about groups are irrelevant to the test score obtained for any individual child. Furthermore, even if IQ testing is a reliable indicator of the capacity for intelligence, the test results suggest nothing about why persons who score high are intelligent.

The revolution in molecular genetics will soon permit us to make a serious attempt at answering that question. Of the 40,000 or so genes that are active at some time or another in human brain cells, it is possible that a much smaller number (perhaps 10 or 20 or 100) play a special role in the development of what we call intelligence. Possibilities include genes that code for neurotransmitters or the receptors with which they interact, genes that control the manner in which nerve cells migrate to their appropriate location in the developing brain, and genes that determine the manner in which nerves become insulated, thus affecting the speed with which information is propagated along them. It is highly likely that scientists will elucidate such genes and, eventually, understand their role in neural physiology.

A few intrepid souls, such as behavioral geneticist Robert Plomin, are already trying. He is using a technique called quantitative trait loci (QTL) mapping to attempt to find alleles that are common in people who have quite high IQ scores, and are less common in persons with quite low IQ scores. Among his most fascinating studies is work he is performing in collaboration with educational psychologists at Vanderbilt University. Since 1998 Peabody College at Vanderbilt has been the home of a long-term project called the Study of Mathematically Precocious Youth (SMPY), often simply called the Stanley Study, in honor of its originator, Julian C. Stanley, who began to study mathematically gifted children at Johns Hopkins University in 1971. Over nearly three decades, the SMPY has collected tens of thousands of children who record dramatically high scores on IQ tests. In 1998 Plomin began to collect DNA samples from a special cohort of children whose scores meet a selection criteria that is only expected in 1 of every 30,000 randomly ascertained kids. He is convinced that his cohort will provide the world's first DNA marker for general intelligence. I doubt he will succeed. If even as few as 100 genes control most of one's potential to do well on an IQ test, each is likely to make only a small contribution (on the order of 1%). It is extremely unlikely that Dr. Plomin will ever be able to perform a large enough study to isolate these effects from the general background and study them further.

Plomin might do far better searching for genes that "cause" intelli gence by first seeking genes that cause mental retardation, a topic on which we have, in some cases, a slightly better grip. We know quite a few genes that must be crucial to intelligence because individuals in whom they are absent or defective have mental retardation. Recently, scientists have begun to map and clone some of these genes, and they have set out on the challenging journey to understand their role in brain function.

In our society, persons with Down syndrome (first described by Langdon Down, a British physician, 150 years ago) represent the archetype of mental retardation. This is because affected individuals look remarkably alike and because the syndrome is so common (appearing in about 1 in 1000 births). Yet, no one even had the slightest guess as to the cause of Down syndrome until 1936 when Lionel Penrose, a British geneticist, offered conclusive evidence that the chances of bearing such a child rose dramatically as women reached their late 30s. Over the ensuing 20 years, this finding spawned much conjecture, but few new facts. The big advance came in 1959 when Jerome Lejeune, a French geneticist, found that persons with Down syndrome invariably have an extra chromosome. This extra chromosome, by convention number 21 (the chromosome pairs are numbered in descending order of size, so this is almost the smallest), is present due to an error in the way chromosomes separate during the formation of egg or sperm cells. About 5% of persons with Down syndrome have the disorder for another reason: In one of their parents the extra chromosome is stuck to another chromosome. That parent has the right amount of genetic material, but it resides on only 45 chromosomes. If the fused chromosome gets passed on, the child will have the normal count of 46 but will have 3 chromosomes numbered 21. In a few cases, such persons inherit only part of the extra number 21.

The scores of physical findings associated with Down syndrome (including short stature, small head, thick tongue, flat cheeks, increased risk for congenital heart defects, short fingers, unusual skin folds on the hands, sunny disposition, and low intelligence) all must arise because of the presence during development of the extra doses of the proteins made by the genes on the extra chromosome 21. By studying hundreds of persons with Down syndrome, especially those persons who have only portions of an extra 21, scientists have begun to define a "critical region" within which the genes that compromise intelligence must lie. That is, they have greatly narrowed the search for the genes that cause the mental retardation.

Using new techniques in molecular genetics, in 1996 Desmond Smith, a British physician-scientist working in California, successfully transferred small chunks of human chromosome 21 into young mouse embryos. These animals have grown up and now represent an exciting new resource for refining our understanding of the role each human gene plays in intellectual functioning. Smith and his colleagues have devised ways to test the intelligence and memory of these transgenic mice. They can then correlate their performance with which portion of human chromosome 21 they carry in their genomes. Because they can create chromosomal chunks of different sizes and study their impact on many animals, the scientists have already greatly refined our understanding of the critical region. This will enhance our understanding of how genes in this region work to support the development of normal and even superior intelligence.

Might we someday be able to use genetic engineering to enhance human intelligence? I can imagine a future when humans will be able to assess the capacity for superior intelligence by performing genetic tests on early human embryos and improving that capacity through gene therapy (Chapter 20). One might argue that we have even taken the first steps on that long journey. In the summer of 1999, Dr. Joe Z. Tsien, an assistant professor of biology at Princeton, published an extraordinary paper suggesting that by adding a single gene to early mouse embryos, he had conferred upon the live-born animals the capacity for doing spectacularly well on the equivalent of mouse intelligence tests. It appears that he did this by enhancing their ability to remember. It has long been thought that the capacity to form memories and success in taking tests that are used to measure intelligence are closely related. In mice a complex molecule called the NMDA receptor, which is assembled from several proteins (each coded for by a different gene), is known to have a huge influence on memory formation. Dr. Tsien reasoned that if he added another gene for a protein called NR2B (which is one of the components of the NMDA receptor) to the two already present in the cells of a mouse embryo, the resulting extra protein in the young mouse would have a positive effect on its neural activities, including memory and learning. He was able to create the trans-genic mouse embryos which grew into mice that can negotiate a maze much quicker than can their unmanipulated relatives. The basis for their superior performance seems to be to that in the cells of the genetically engineered mice the altered NMDA receptor stays open about 150 thou sandths of a second longer than do regular cells. Predictably, the report of a "smarter mouse" provoked an invasion of journalists, all asking when the techniques would be ready for human use.

Even cursory reflection on the immense complexity of the human brain, an organ with billions of cells involved in trillions of interconnections, and operating in an ever-changing pattern, makes the hubris of anyone who would attempt such actions with current knowledge laughable. Still, we may have started on a journey that will someday result in our learning how to genetically enhance intelligence. If so, I am glad it is still a long road, for we are clearly not yet mature enough to be able to use such skills in ways to benefit humanity and its fragile home. Until we mature as a species, it is surely better that the origins of intelligence, musical and artistic talent, athletic prowess, and the thousand other qualities that make us fascinated with (and envy) each other remain elusive.

Dean H. Hamer, Ph.D.

Was this article helpful?

0 0

Post a comment