The DNA Files: Unraveling the Mysteries of Genetics

“DNA and Behavior: Is Our Fate In Our Genes?”
Transcript

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“DNA and Behavior: Is Our Fate In Our Genes?”
Transcript

[Theme Music]

JOHN HOCKENBERRY: This is the DNA Files, I'm John Hockenberry. Is our fate in our genes? Is there a fat gene, a smart gene, or a gene for aggression?

DEAN HAMER: Of course, the gene doesn't whisper in your ear, "go bungee jumping."
Genes aren’t that smart or that powerful.

LEE SILVER: There is no such thing as nature versus nurture; it's nature and nurture. Almost every aspect of who we are is based on an interaction between the two.

JOHN HOCKENBERRY: To sort out the nature of genes from the influence of environment, scientists have constructed twin studies, mouse studies, they even use personality tests. But will knowing what we’re made of tell us anything about who we are? Listen as we explore "DNA and Behavior."

But First.....

Consider the cruelty of the disease schizophrenia, tearing young men and women from their families, plunging them into a nightmare of paranoid delusions and sinister inner voices. Crueler still, for much of this century, science blamed parents for their children’s inner agony. We know now that schizophrenics have a brain disease, but the search of causes has lead scientists into a labyrinth of environmental factors and genetic inheritance as John Rieger reports.

[Sound of father reading Green Eggs & Ham:]

“Ok. Where were we? Would you eat them in a box?”

JOHN RIEGER: No matter how much we love and cherish them, one child in 100 will be schizophrenic. It strikes typically at the first flowering of adulthood with hallucinations and paranoid delusions that ravage family bonds. And until about twenty years ago, psychiatrists blamed it on bad mothers.

DR. E. FULLER TORREY: Were I to guess, I will guess that when she died, she still felt guilty that somehow she had caused it, because after all, that’s what the big doctor said.

JOHN RIEGER: Dr. E. Fuller Torrey saw his own sister develop schizophrenia at seventeen, and he watched his mother shoulder the blame. An avowed enemy of pumpkin headed psychiatry, he’s helped spark a revolution in how we understand schizophrenia.

DR. E. FULLER TORREY: This is a brain disease.

JOHN RIEGER: Torrey was co investigator in a landmark study of schizophrenia in twins. In sixty eight pairs of identical twins, twenty eight pairs were discordant for schizophrenia. Meaning one twin had it and the other didn’t.

DR. E. FULLER TORREY: What we found was that there were clear differences in both brain structure and function despite the fact that they have the same genes.

JOHN RIEGER: Now, that’s a puzzle because schizophrenia runs in families. In the general population it strikes one in a hundred. But children of schizophrenics are ten times more likely to be affected. So, it appears to be genetic. But the twin study shows it’s not that simple. Steven Hyman is director of the National Institute of Mental Health.

STEVEN HYMAN: Even twins who share 100% of their DNA are both affected with schizophrenia only about 40% of the time. So, that means since they share all of their DNA that some non genetic factors must be involved in producing the illness.

JOHN RIEGER: This could be good news. Maybe your genes make you vulnerable to schizophrenia, but some factor in the environment makes you sick. Find the environmental factor, and perhaps you could prevent the disease. But the missing factor may be random. Steven Hyman.

STEVEN HYMAN: You know identical twins have different fingerprints, and they have different patterns of folds in their brain. There simply isn’t enough information it the genome to encode the precise detail of…of the connections among the hundred billion neurons in the brain. And so while genes create the overall blueprint for each person, uh there is a certain amount of simply uh random developmental effects in wiring up the brain. And then, the environments acts to shape and sculpt those connections.

JOHN RIEGER: The genetics of schizophrenia is also complex. Identical twins have all the same genes. Fraternal twins share only half their genes. If a gene causes schizophrenia, then identical twins should both be schizophrenic about twice as often as fraternal twins. But in fact, the ratio is five to one, which means that schizophrenia involves not one gene but an unknown number of genes.

STEVEN HYMAN: This has been a major area of research for the last ten years, and unfortunately has not been very productive.

JOHN RIEGER: Dr. Torrey says the gene hunters won’t succeed. He believes the environmental factor in schizophrenia is a virus.

STEVEN HYMAN: I think that we can look for a gene or genes that cause schizophrenia from now for the next 150 years and we’re not going to find them. What we need to do is identify the environmental agent, viral or otherwise that actually gets in the brain. I think that over the next five years we will identify genes that cause vulnerability to schizophrenia….

JOHN RIEGER: Steven Hyman.

STEVEN HYMAN: …and this will launch an enormous flowering of research which is going to take those genes and use them as tools of inquiry in the brain to say, you know, what is it that’s going wrong in these brains? And then another group of scientists are going to be able to ask, are there modifiable environmental factors that are taking this genetic risk and making people sick uh so we’ll have a great uh flowering I hope of research on environmental factors and indeed prevention research.

[Sound of father reading Green Eggs and Ham]

JOHN RIEGER: But for now we haven’t found any genes. We don’t know what the environmental factors are. We can’t predict who will become schizophrenic, but we know it will be one in a hundred worldwide. And we know it’s not caused by bad parents.

[Sound of child laughing]

JOHN RIEGER: I’m John Rieger for the DNA Files.

[music]

JOHN HOCKENBERRY: This is the DNA Files. I’m John Hockenberry.

[Sound of airplane]

Everybody is different. I, for one, would not care to throw myself out of the open door of an airplane, flying almost three miles above the ground. Hey, but Jeff Talbot gets a thrill from doing just that. He is what some people call a “novelty seeker.”

JEFF TALBOT: I'm a big jumper. I jump off cliffs, waterfalls. Just uh....It's fun. (Laugh)

JUMP INSTRUCTOR: OK, turn around. You'll be tempted to want to flair or slowdown the parachute before I give the command, but you don't want to trust your own instincts, you want to trust mine.

[Sound of roar of plane as door opens]

JUMP INSTRUCTOR: It's going to be 120mile per hour wind force..... Ready, set....(whoosh!)

GROUP IN PLANE: Whoopee!

[Sound of plane fades into background]

JEFF TALBOT: Ha ho. Nothing like it. Oh, just incredible!

JOHN HOCKENBERRY: Novelty-seeking, which is kind of a clinical term from people from people who like to perform stunts like jumping out of planes, is just one of the many personality traits behavioral geneticists are studying. These scientists are trying to discover if there is a connection between the way one acts and one’s genetic make-up. Long before scientists posed the question, it’s been the stuff of family lore.

[Sound of classical music under the Dinner Party Scene; Random voices overheard at a big family dinner party:

WOMAN: "But she does have your fine ear for music."

CHILD: (Laughter)

MAN: "And her Uncle Herbert's sense of humor."

JOHN HOCKENBERRY: One’s sense of humor is not something that is “passed down” from Uncle Herbert. The only thing that is actually passed down – or inherited – are genes. Scientists are just beginning to unravel the physical process of how genes influence specific traits – like a sense of humor. Human beings each have between 80,000 and 100,000 genes within each cell of our bodies. These genes are organized into 23 pairs of chromosomes, including the X and Y, the famous chromosomes that determine a person’s sex. Since the 1950s, scientists have understood that our DNA is a “code” that regulates what our body looks like and how it operates. New research in genetics, molecular biology and neuroscience shows us that genes are also a factor in the make-up of our personality. But what do we mean by “personality”? Robert McCrae, a research psychologist at the National Institute on Aging, has been studying personality for the last 20 years.

ROBERT MCCRAE: Personality traits are characteristics that differentiate one person from another and that give people continuity over time; they're enduring aspects of what you're like. So, personality traits are likely to be expressed in what you think, and in your beliefs, and attitudes, and your feelings, and your emotional vulnerabilities and reactions, all those kinds of things would potentially be part of your personality.

JOHN HOCKENBERRY: But what creates our personality? Where does it come from? After years of debate, scientists now agree that every facet of our personality is created through a complex interaction of both genetics and environment. It’s clear that we are not born “a blank slate” to be molded purely by our environment. It is also clear that our personalities are not rigidly “hard-wired” by our bodies. Our genes do not “predetermine” our fate. But they can create a “predisposition” towards a trait that gets triggered by something in the environment. For instance, a child may have a genetic propensity towards shyness. And faced with a domineering teacher, the child may become even more withdrawn. And here’s where scientists don’t agree. What has more influence on our personality, genetics or environment?” Behavioral geneticists are investigating personality traits to discover whether and to what extent our genetic make-up influences the way we act.

ROBERT MCCRAE: I could give you a list of about 18,000 trait names in the English language. You can be nervous, extroverted, silent, curious, straightforward, down to earth...... um, those kinds of characteristics.

JOHN HOCKENBERRY: This program – “DNA and Behavior: Is Our Fate In Our
Genes?” -- will take a close look at three personality traits – sexual orientation, addiction and novelty-seeking you heard about earlier. In the next hour, we'll explore the interplay of genetics and environment on these traits. We'll learn the distinction that scientists make between personality traits and culturally-based behaviors. And we'll talk to the scientists who are busy figuring out what makes us tick.

[Sounds of a parade. Shouts, drums, music.]

Voices Chanting: “People with AIDS, under attack. What do we do? Go fight back!”

Man in Crowd: ”It's OK to be Gay. There's no fear to be queer. You know, it's beautiful.”

JOHN HOCKENBERRY: More than 200,000 people from all walks of life and sexual orientations turned out to watch or march in San Francisco's 28th annual gay pride parade. But out of all those people, what makes someone gay? Male and female physical attributes are genetically determined. That much is obvious. But understanding what makes one attracted to the opposite sex or the same sex is not so straight forward. The debate over whether being homosexual is inborn or learned has
Been going on for quite some time. But are we even asking the right question? Dr. Lee Silver, Professor of Genetics at Princeton University, doesn't think so:

LEE SILVER: There is no such thing as nature versus nurture; it's nature and nurture. Almost every aspect of who we are is based on an interaction between the two. And so it's this very, very powerful interaction between genes and the environment which is always at play in almost all aspects of who we are.

JOHN HOCKENBERRY: Dr. Pilar Ossorio studies ethical issues associated with genetic medicine and genetic research at the American Medical Association's institute for ethics:

PILAR OSSORIO: It's not as though you could melt down the person and then you would have, "Oh, this bit is environmental, and this bit is genetic."

LEE SILVER: When we're talking about environment, we're talking about every single stimulus that comes into our bodies from the moment we're conceived up until we are born. We're talking about the way people talk to us, the food that we eat, the air that we breathe, the position of the
fetus inside the womb. The environment is many, many times more complicated than our genetics, and we're never going to understand it completely. So the environment is really everything other than the genes.

JOHN HOCKENBERRY: To make things more complicated, the part of the equation that is genetic is rarely influenced by a single gene. Pilar Ossorio:

PILAR OSSORIO: For the most part, it's not going to be the results of any single gene directly and only affecting some kind of characteristic. It's going to be a complex interplay between any number of genes, some of which might not seem all that related. You know, things that have to do
with sexuality might have to do with how you see colors, how you smell things, even though people might think it would be strange to say that "Oh, a gene that affects how you smell is a sexual orientation gene."

JOHN HOCKENBERRY: Popular culture sometimes confuses the "nature/nurture debate". For instance, film plots often foster the idea that personality is directly inherited from one's genes. "The Bad Seed" made back in 1956 was one such gem. Patty McCormick plays Rhoda, a darling
little girl, brought up in a perfect home with loving parents, but with an unfortunate propensity towards murder........

[Sound of suspense music]

JOHN HOCKENBERRY: Which, it turns out she inherited from an "evil" grandmother.

THE VISITOR: They cite a type of criminal born with no capacity for remorse of guilt. No feeling of right or wrong.

THE MOTHER: You really mean to say that nice family surroundings and advantages could make no difference at all?

THE VISITOR: It's just that they are bad seeds. Plain bad from the beginning. And nothing can change them.

JOHN HOCKENBERRY: Over the first half of this century, the idea that our personality is influenced by heredity moved in and out of favor in the popular culture. But modern scientific inquiry into the matter didn't begin until the 1960's. While scientists understood the basic concept of inheritance, there was no way to isolate and observe individual genes. They devised a method of examining the influence of inheritance on personality based on the study of identical twins. Until the 1950's twin studies were the only method scientists had to try to trace a biological role in behavior. Over a dozen twin studies on male sexual orientation have been done in the past 40 years.

Reporter Jackie Northam looks at one recent twin study of gay men:

JACKIE NORTHAM: Identical twins share the same genes. So by studying twins, researchers hope to determine if genes have an impact on personalities or behavioral traits.

DOUG WIDENER: One of the things that makes us different that is on the top of my head is that is that I can roll my tongue and he can't.

DAVE WIDENER: So watch Doug just do - now see that's not a very good tongue roll. That’s barely one at all, and then, look. See.

DOUG WIDENER: But I can do some things better than he can too. So…
(laughs)

JACKIE NORTHAM: Dave Widener might be able to roll his tongue better than his brother Doug. But they figure that's one of the few differences between them. The 28-year-old identical twins not only look alike but they say they enjoy the same music, food and sports. And they're both gay.
Could there be a link between their identical genes and their sexual orientation? To find out the answers to questions like this, psychologists Michael Bailey, with Northwestern University near Chicago and Richard Pillard, with Boston University, have done two twin studies on male homosexuality. Dr. Michael Bailey says they drew from a limited sample.

MICHAEL BAILEY: We recruited our twins by advertising in gay and lesbian publications and the advertisements basically said “Are you a twin - if so, call us.” In our first study we had about 50 sets of identical twins and about 50 sets of fraternal twins. We also had a third group who were not twins but these were adoptive siblings.

JACKIE NORTHAM: What Bailey and Pillard found was that the identical twin of a gay man stood about a 50% chance of being homosexual himself. Those figures dropped to about 20% for fraternal twins - they share only half their genes. Those chances dropped even further for the biological or adoptive siblings.

MICHAEL BAILEY: I would say that our results greatly increase the probability that there is a gene or that there are genes for sexual orientation in both males and females. However, it would be good to do an even better study.

JACKIE NORTHAM: Many scientists agree that more sophisticated studies need to be done before conclusive results can be made about the relationship of genes to personality traits. It's not like eye or hair color which are genetically determined. And Professor Jon Beckwith, a geneticist at Harvard Medical School, says twin studies in particular are riddled with problems.

JONOTHAN BECKWITH: To begin with, I would say that people doing the twin studies have started off with very simplistic ideas of how you go about studying very complex behaviors such as homosexuality, or intelligence, etc. I think identical twin studies where you look at twins born with exactly the same set of genes, would appear on the surface to be good kinds of experiments to do. But in fact, it turns out that there are a lot of complexities that are ignored and in fact I think they are much better at showing up in environmental effects then they are in really establishing genetic effects.

JACKIE NORTHAM: Beckwith says twin studies ignore the complex role environment plays.

JONOTHAN BECKWITH: Environment obviously goes back to how they develop within the womb. And there are lots of studies coming out now that suggest that in the womb itself there are differences in the way different twins develop.

JACKIE NORTHAM: Bailey agrees that the environment is a crucial factor for personality traits - but he defends the studies saying they were able to determine a pattern of similarity in relatives for homosexuality.

MICHAEL BAILEY: At the conclusion of a twin study, usually what you're going to be able to say is something like ‘genes sure seem to be important or genes don't seem to be very important' - you're not going to be able to say 'there seems to be a gene on chromosome 21 that affects this trait'.

JACKIE NORTHAM: But Bailey does acknowledge problems with his studies, including how the participants were recruited. Placing ads in gay magazines created a certain bias he says. When he did a later study in Australia, using a broader spectrum of twins by searching that country's
twin registry, Bailey's findings were strikingly different than the American studies. The identical twin of a gay man in the Australian study stood about a 25% chance of being gay himself. That's about half the figure found in the American study. However, Bailey says this study also
found that just under 10% of fraternal twins had a gay brother. So, what does that mean? Even though the numbers were lower, the ratio between the identical and fraternal twins stayed constant -- still showing the genetic influence.

MICHAEL BAILEY: I think that the sampling method in this Australian study is clearly preferable to the way that we did it in America and so these new numbers, I think, are more trustworthy.

JACKIE NORTHAM: But what these numbers call into question is how misleading statistics and findings can be. Twin studies rely on something called a heritability estimate which illustrates how much a particular behavioral trait can vary - both genetically and environmentally. Scott
Stoltenberg, a behavioral geneticist at the University of Michigan, says heritability estimates were first designed by plant and animal breeders as a way of determining which traits would be good for selection - like the numbers of ears of corn or percentage of milk production. But Stoltenberg
says this system is flawed when it refers to humans.

SCOTT STOLTENBERG: The statistics then were sort of taken over by people that did human behavioral genetics because well, there really wasn't much else out there I think to try to learn about human behavior genetics with because, you know, you can't do selective breeding with humans and, you know, there are a lot of things you can't do with humans.

JACKIE NORTHAM: Even behavioral geneticists emphasize that these statistics really only apply to populations, not individuals. They cannot tell us to what extent genes influence a trait in any individual. Dr. Richard Lewontin, a molecular geneticist at Harvard University, says whatever studies are used, he has no doubt sexual orientation is a mixture of genetics and environment. But, he adds, so what?

RICHARD LEWONTIN: The question is once the studies are done, and even if they
were perfect, what would they tell you that you want to know: What is it
I'm trying to find out, What am I trying to do about sexual preference? Am
I trying to change peoples' sexual preference? I think the argument that
it's interesting to know whether genes influence or don't influence, for
example, sexual preference is a bad argument. I don't want to know that, I
don't care, it doesn't mean anything to me.

[Sound of Doug and Dave in the kitchen, rattling dishes, talking.]

JACKIE NORTHAM: But back in the Widener kitchen, the debate about genetics and sexual preference strikes an emotional chord with the twins. Dave, the older twin by four minutes, has fears about the repercussions of genetic research.

DAVE WIDENER: Just think about it, if there is a gene that says, say that you know gray eyes are unattractive, you know, if we could filter out a gray eye gene, you know, that would be scary and parents can say let's filter out this gene. And parents can say, let’s filter out this gene, you know.

JACKIE NORTHAM: But his brother Doug says research can only go so far in determining a person's behavior.

DOUG WIDENER: No matter how similar Dave and I are, I'm…I’m unique and
there'll never be another Doug Widener on this planet ever, you know, that exhibits exactly the exact same traits that I do.

JACKIE NORTHAM: Which is why it will likely be a long time, if ever, before scientists can understand the complex interaction of nature and nurture.

[Theme Music]

JOHN HOCKENBERRY: Jackie Northam found that the influence of heredity in homosexuality is a complex and touchy issue. People's opinions about the scientific work done in this area are often colored by their feelings about homosexuality itself. Pilar Ossorio:

PILAR OSSORIO: Certainly there's a portion of society today, which is very opposed to homosexuality, which considers it a lifestyle, a choice and more than that, considers it a sin. So, you could ask, "Will doing this research change people's attitudes in any way?" And particularly, will this diminish the stigma that's associated with homosexuality in any way? Will it cause people to change their attitudes and become more accepting or understanding of homosexuality?

JONOTHAN MARKS: Whether or not homosexuality is genetic is not going to influence what homophobes or homophiles think about the behavior. Their attitude is going to be framed independently of what science has to say.

JOHN HOCKENBERRY: Jonathan Marks is a biological anthropologist at the University of California at Berkeley.

JONOTHAN MARKS: The Nazis felt that homosexuality was inherited, and that therefore to get rid of homosexuality, all you had to do was kill all the homosexuals. The reaction to that after the war, of course, was to say, "Well, it's not genetic. It's learned." And this was conventionally
accepted wisdom until homophobes discovered that homosexuals were teaching in the public schools and said, "Well, if homosexuality is a learned behavior, we can't have homosexuals teaching our children, can we? Because they'll be teaching our children buggery." This does have social consequences.

JOHN HOCKENBERRY: The question is, do people mostly choose their personality traits from some preference, or do they live out some predetermined organic scenario in their personalities? The debate is the high voltage that drives so many controversial issues in policy and politics. Let’s take the question of addiction. If addiction is a choice, you would deal with it one way. But if it’s beyond our control and we can prove that addiction is genetically determined, it would suggest a completely different strategy.

[Sound of jukebox at the bar; loud voices in background]

BARTENDER #1: We get a little of everything, I mean you have....we have a lady who comes in here and basically, drinks half a bottle of wine, takes off, comes back a couple of hours later, and orders the other half bottle of wine. You will have your regulars. They just need their, their fix I
guess.

JOHN HOCKENBERRY: What makes someone an alcoholic? What exactly do we mean by an "addictive personality"? Lee Silver studies this trait:

LEE SILVER: When a person becomes addicted to a substance they have a craving for that substance. And they also have withdrawal symptoms. So, if the stop smoking or they stop taking alcohol they get sick from not having the drug and they need the drug to overcome their sickness.

JOHN HOCKENBERRY: What distinguishes someone who is addicted to alcohol from the rest of us who might simply have one too many at a party?

LEE SILVER: Addiction has to be distinguished from abuse. It's not just a question of how much alcohol is drunk; it's a question of whether the alcohol is being drunk because of a need, a physiological need, to do the drinking. So there are actually many college students who over drink,
abuse alcohol in a serious way every weekend during their college career; they graduate college, they grow up and they never have a problem with alcohol because they never became addicted.

JOHN HOCKENBERRY: But why can some people control their drinking and others can't?

LEE SILVER: Some people are born with a genetic predisposition towards addiction. So that these people have a particular genetic constitution that when they drink, they will become addicted.

JOHN HOCKENBERRY: So do certain genes make one an addict? Not really. They are simply codes from which proteins are manufactured. These proteins play an important role in mind and body function.

LEE SILVER: Genes operate very indirectly. They are the instructions for making proteins. And these proteins carry out different functions in our body. So, some proteins operate to digest the food that we eat every day. And other proteins act as receptors to receive neurotransmitter signals.

JOHN HOCKENBERRY: Neurotransmitters, in turn, allow signals in our brain to be sent from one nerve cell to the next -- the basis of brain function. Two neurotransmitters -- serotonin and dopamine -- seem to play a crucial role in the sending and receiving of signals which influence our
personality.

LEE SILVER: Serotonin and dopamine are used by nerve cells that play a roll in personality traits and in emotive kinds of behaviors – things like curiosity, anxiety, aggression.

JOHN HOCKENBERRY: How did scientists figure out this gene-protein-neurotransmitter connection? Well, it's now possible to actually isolate the DNA from an animal's cells in order to, in theory, identify specific genes that might influence personality traits. So, while twin studies
may still provide useful information, geneticists can now design studies that look at the genes themselves. Animal studies offer an important model for scientists who hope their results will eventually apply to humans. Studies of mouse DNA look especially promising. One behavior being intensively examined is addiction. In these studies, scientists have isolated specific genes that seem to help regulate the use of both serotonin and dopamine in the brains of mice.

Robin Marks reports now on a research team looking at neurotransmitters at the Veterans Administration Medical Center in Portland, Oregon:

ROBIN MARKS: Science has a long, if some what checkered, history of animal experimentation. Remember Pavlov's dog? That research formed the backbone of our knowledge on behavioral conditioning. Dogs, cats, monkeys and mice continue to be used in behavioral studies and today that includes the genetics of behavior. Researchers are particularly interested in behaviors associated with disease, such as alcoholism.

[Sound of laboratory; people talking]

ROBIN MARKS: The Veterans Administration Medical Center has a wing filled with mice, cages and testing apparatus. Some of the testing devices are simple constructions-- no more complicated than the police test of walking a straight line. Others are a bit more elaborate. Behavioral geneticist Tamara Phillips:

[Sound of cage opening]

TAMARA PHILLIPS: This is called a grid test and it measures end coordination produced by drugs. So, normally an animal, when you place it in this chamber, there is a grid floor, it will walk around on that grid floor -- it’s just made of hardware cloth -- without it's feet slipping through. But if you give it alcohol it becomes very ataxic and discoordinated and it's feet start to slip through and make contact with this metal plate, that's lying here.

ROBIN MARKS: Given an adequate amount of alcohol, all mice will stumble on the grid. But, says Phillips, the mice who stumble less may have a greater chance of becoming addicted. This test helps researchers isolate how sensitivity to alcohol fits into the addiction process. The research group conducts a variety of experiments that look at discrete parts of the process. Some experiments look at differences in preference for alcohol. Others examine how much mice come to tolerate alcohol's effects. And still others test a rodent's reaction when alcohol is taken away.

JOHN CRABBE: You pick them up by the tail and there's a very mild -- like a tremor and convulsion that they have that human alcoholics would have too if you didn't give them valium in the ER.

ROBIN MARKS: John Crabbe is Director of the Portland Alcohol Research Center and a behavioral neuroscientist.

JOHN CRABBE: …get better over twenty four hours. So we monitor that sign to estimate how dependent they were and there's big individual differences. Some of them show nothing at all, some of ‘em show big long signs of dependence.

ROBIN MARKS: To search for genes associated with dependence, Crabbe and Phillips breed mice with severe withdrawal signs together and mice with mild withdrawal signs together. By creating mice whose behavior is at either extreme, researchers can test for genetic differences. John Crabbe
says this research method will eventually help locate similar genes in people.

JOHN CRABBE: Cumulatively over a lot of different kinds of experiments and approaches you can use it to identify the specific genes that have been changed by that breeding program and 85% of our genes are the same as what mice have. So, that if you can find genes that lead to extreme responses in mice, it's very likely then that you would then know where to look in humans for the same genes.

ROBIN MARKS: Mouse studies have disadvantages. Mice can’t tell scientists about peer pressure or other social influences. Also, mice are very inbred, humans are not. And that makes the genetic correlation between mice and people harder to do. But Tamara Phillips says there is one huge advantage.
TAMARA PHILLIPS: For me it’s being able to control the environment so that I can separate that out from the genetics and actually determine what part of this behavior is genetically determined, what part of this behavior is environmentally determined. It's extremely difficult to do that in human populations.

ROBIN MARKS: Controlling the genetic makeup of mice is another key advantage. Phillips and Crabbe occasionally use " knockout mice"—mice with a specific gene removed or knocked out. Phillips and Crabbe use knockout mice for studies involving dopamine and serotonin – brain chemicals that affect mood and motivation in people -- including, perhaps, the ability to control the impulse to drink. John Crabbe:

JOHN CRABBE: These animals grow up lacking one of the fourteen different kinds of serotonin receptors and it turns out they drink twice as much alcohol by choice as their normal counterparts. So that is pretty suggestive that that gene is playing a fairly important role.

EVAN BALABAN: If I tell you there's a gene that seems to be correlated, that variation in this gene is correlated with variation in a behavior, what have I explained by telling you that? (chuckle) I really haven't explained very much. 3330

ROBIN MARKS: Evan Balaban is a senior research fellow at the Neurosciences Institute in San Diego. He says alcoholism isn't just a biological problem and genetics is a narrow lense through which to view addiction.

EVAN BALABAN: Whatever John Crabbe is studying will have some bearing on understanding how alcohol is metabolized in a body and the effects that alcohol has on cells of the body, including cells of the brain. And the problem with going from that to statements about alcoholism is that alcoholism is much more complicated than that, because it involves things about emotions and thoughts and feelings that are in and of themselves not directly connected to the way that cells are metabolized or affected by alcohol.

ROBIN MARKS: Balaban's arguments are bolstered by the fact that results from mouse studies don't always hold up in human studies. It's difficult to know why. Environment, study design, differences not yet understood between mice and people, could all be factors. Crabbe says it's important to chisel away at these questions and over time the larger picture will
emerge.

JOHN CRABBE: There isn't a gene for alcoholism. There's not five genes for alcohol. Any of us doing this work would weigh in an say, OK, maybe there's 10, maybe there's 50. It's hard to tell the
difference once you get above about three. These aren’t major gene disorders. They’re polygenic disorders, so there are lots of genes out there and we assume that each one of them notches up or down your risk by a little bit. So what you have to do is capture enough of them that in the aggregate you can really get a handle on increasing or decreasing risk.

ROBIN MARKS: DNA can only tell part of the story of human addiction. Just how large or small a part genes play is far from known. For now these researchers proceed on the hope that deeper knowledge of alcohol addiction will one day lead to better treatment of a difficult disease.

[Theme Music]

JOHN HOCKENBERRY: This is The DNA Files.

JOHN HOCKENBERRY: This is The DNA Files. I’m John Hockenberry. You often hear people say, "if he really wanted to stop drinking, he would." But it may not be so simple. Robin Marks found that genetics may play an important role in addiction. And as we understand more about addiction, how will that research change our attitudes outside of the laboratory? Lee Silver and Pilar Ossorio:

LEE SILVER: I think when an alcoholic person who has such a hard time stopping drinking discovers that he is addicted because of something in his genes, it could give him a sense of relief. It's taking away the notion that the reason people are alcoholic is because they have a character flaw.

PILAR OSSORIO: We tend to think that if we can discover a biological basis for some behavior that that somehow diminishes the responsibility that a person has for doing that behavior. Well, everybody might have propensities to do something that our society disapproves of. And it's one's obligation to overcome that propensity.

JOHN HOCKENBERRY: Can genetic research ultimately help overcome a propensity towards alcoholism?

LEE SILVER: If we understand the molecular basis for addictability, we may be able to find a cure for it. If we understand the genes, we'll be able to figure out what proteins those genes make and then hopefully we'll be able to figure out a way of overcoming the addiction much more easily.

JOHN HOCKENBERRY: And some people worry that finding a genetic propensity may lead to dangerous consequences. Tests for drug abuse are now common. Why not tests for a genetic propensity towards drug abuse or alcoholism?

PILAR OSSORIO: There's also a concern that there might be problems with discrimination--job discrimination, discrimination of people's ability to get into the military, discrimination in terms of their ability to get insurance. This is a really pretty serious concern.

LEE SILVER: Just because somebody is addictable to alcohol does not mean that they're going to be drinking on their job. And so their genetic profile should not be used. The way they behave should be used.

JOHN HOCKENBERRY: Alcoholism and homosexuality are both emotionally charged issues. Geneticists are also curious about some less controversial traits -- ones that we all share to some degree or another. They call them "normal-range" personality traits. Whether you tend to be happy-go-lucky or have a grumpy disposition, whether you are a quick study in school or struggle with every test, whether you have perfect pitch, a quick sense of humor or a hot temper -- these are all controlled -- at least in part – by the genetic make-up of your DNA. Dr. Robert McCrae:

ROBERT MCCRAE: Talkativeness is a normal range trait, because there's all kinds of variation and some people are very talkative, some people are not talkative at all, and most of them are somewhere in between. And you don't have to have a disorder of some kind to be relatively silent or to be relatively talkative.

JOHN HOCKENBERRY: One group of traits that psychologists like Robert McCrae are looking at are called "novelty-seeking".

ROBERT MCCRAE: People who are high in novelty seeking are extroverted and they are cheerful, and active and fond of excitement. So they're not persistent, they are not deliberate and cautious.

JOHN HOCKENBERRY: But what makes one person love going to parties filled with strangers and someone else prefer to stay at home with a great book? Geneticists are studying a number of what scientists call "normal-range" traits to try to figure out how much is genetically based
and how much is environmentally influenced. Which genes actually play a role and how they do it?

[Sound of New York City Street; people and cars]

JOHN HOCKENBERRY: The first step for these researchers is to determine the level of a trait -- like novelty seeking for instance -- that an individual test subject may have. How do they do this? They simply ask people. The researchers give them "personality quizzes" like this one I'm holding right now, as I wander down Manhattan's 5th avenue. There must be plenty of thrill-seekers in this crowd.....You, you -- excuse me. Can I ask you a couple of questions? I work for Public Broadcasting. My name is John Hockenberry. How are you?

EMILY: I’m fine.

JOHN HOCKENBERRY: We're doing a program on personality and genetics. OK. And I just want to give you a very short personality quiz to see if we can learn anything about you. Alright?

EMILY: Uh oh.

JOHN HOCKENBERRY: Your response to these questions should be “agree,” “strongly agree,” “disagree” or “strongly disagree.” Alright? OK.

EMILY: OK.

JOHN HOCKENBERRY: And what's your name?

EMILY: Emily.

JOHN HOCKENBERRY: Emily. Alright. Emily. Do you think it’s conceivable that your personality is genetically based?

EMILY: Yes.

JOHN HOCKENBERRY: Really?

EMILY: Yeah.

JOHN HOCKENBERRY: Now, if they determine to some precise degree how genetically based your personality was, would you take it in for an overhaul?

EMILY: What do you mean? Like can you rephrase that?

JOHN HOCKENBERRY: Yeah, if they could…if you could manipulate your personality by…

EMILY: Oh, by genetically changing it?

JOHN HOCKENBERRY: Yeah. Right.

EMILY: No.

JOHN HOCKENBERRY: You wouldn’t change anything?

EMILY: No.

JOHN HOCKENBERRY: Would you suggest that she change something?

[group laughs]

MALE COMPANION: No. No. I wouldn’t suggest it at all.

JOHN HOCKENBERRY: Good. Alright.

EMILY: Not even my sense of direction?

[group laughs]

MALE COMPANION: OK. That’s right - sense of direction.

JOHN HOCKENBERRY: So, if you could get a better sense of direction genetically, you’d do that?

MALE COMPANION: Yeah

EMILY: Yeah, probably.

MALE COMPANION: If possible.

[music]

JOHN HOCKENBERRY: Um…what’s your name?

DIANE: Diane.

RICK: Rick.

JOHN HOCKENBERRY: OK. How would you respond to this question. And your answers can be “agree,” “strongly agree,” “disagree” or “strongly disagree.” OK? “I like to try new foods that I've never tasted before.”

DIANE: Strongly agree.
JOHN HOCKENBERRY: Strongly agree. And you?

RICK: Strongly disagree.

JOHN HOCKENBERRY: Strongly disagree...whoa. whoa!

DIANE: He's very rigid when it comes to food. He does not like to try new things and so...

JOHN HOCKENBERRY: I see....

RICK: But I'll get on a plane and go to Thailand for a month so...

DIANE: Right.

JOHN HOCKENBERRY: With a lot of hamburgers I guess....

DIANE: Right. He won’t…he won’t eat the food there.

[music]

JOHN HOCKENBERRY: …a personality quiz, is that OK?

BRYCE: Sure.

JOHN HOCKENBERRY: Alright, what's your name?

BRYCE: Bryce.

JOHN HOCKENBERRY: And your name?

NIKA: Nika

JOHN HOCKENBERRY: Great. This is an actual personality test that, you know, psychiatrists and psychologists have developed.

BRYCE: Uh oh.

JOHN HOCKENBERRY: 'I have no patience with dull and boring persons.'

BRYCE: Disagree.
JOHN HOCKENBERRY: Disagree.

NIKA: Strongly disagree.

JOHN HOCKENBERRY: Strongly disagree? So you have......

NIKA: Nobody's dull to me.

JOHN HOCKENBERRY: Oh really?

NIKA: No.

JOHN HOCKENBERRY: So you have infinite patience for dull and boring people. That's…that’s a personality trait.

BRYCE: We're putting up with you aren't we?

[laughter]

JOHN HOCKENBERRY: There you go!

BRYCE: Just kidding.

JOHN HOCKENBERRY: I opened the door, and you broke through.

[music]

JOHN HOCKENBERRY: So, I’ve made some new friends here but what have I learned. Psychologists like Robert McCrae spend years designing just the right balance of questions in these sorts of tests.

ROBERT MCCRAE: The most common way to assess personality is by asking people to describe themselves in terms of a fixed set of questions that are relevant to whatever it is you’re trying to measure. Any one single answer may not be very accurate, and you want to make sure you that understand what the person is trying to say by asking a similar question many times

JOHN HOCKENBERRY: But just how useful is a test like this? Jonothan Marks thinks these tests have little value.

JONOTHAN MARKS: The problem with self identifications, especially for things like personality or behaviors is that people either kid themselves or they kid you about what they really are. There is no doubt in my mind that in most cases, and for most purposes you can evaluate people’s personalities reasonably well. And the evidence from that comes from many many studies showing that these assessments predict responses to a particular situation.

JOHN HOCKENBERRY: A bigger question is whether the whole idea of normal range traits is valid. Is there even such a thing as novelty seeking? Marks proposes that these traits are not inherent in the human species but varied between cultures.

JONOTHAN MARKS: Americans today, for example, are very very homogeneous in their behaviors. Sure, Newt Gingrich and Jessie Jackson might look different, sound different, act different. But on a global scale, if you take the most heterogeneous group of Americans and put them in a room, the one sherpa from Nepal is going to stand out very very distinctively. And the difference between that one sherpa from Nepal and all of those heterogeneous Americans is not genetic. It’s cultural. It’s the result of historical, social processes that have nothing whatsoever to do with genetics. Behavioral differences in the human species occur much more extensively between groups of people than they do within groups of people.

ROBERT MCCRAE: We have to make a distinction here I think between traits and behaviors. Personality traits are dispositions. They’re tendencies. Behaviors can be different in different cultures. They can be different at different points in the life span. Shooting guns is not something that you have a gene for. But being aggressive may well be something that is influenced by genes.

JOHN HOCKENBERRY: Robert McCrae says that if you are an aggressive person, it doesn’t matter where in the world you live. You are going to find ways to be aggressive.

ROBERT MCCRAE: You may use guns. You may use knives. You may use harpoons. But human beings have found ways to be aggressive in every possible circumstance. And if you have that personality trait, you’ll find a way to express it. So, we have to distinguish between the underlying tendency that’s very general and abstract, a very broad potential and then the concrete behaviors that express it, that act it out at any particular time and place.

JOHN HOCKENBERRY: Traits like nurturing and aggression are also being studied through animal models, the human and mouse genome are very similar, so that often the same gene produces the same protein which influences the same neurotransmitter. But whether this neurotransmitter actually results in the same personality trait, is still very much in question. Mouse studies can’t tell us everything. Scientists are now conducting studies with humans as well as animals to identify specific genes which influence personality traits. These are called genetic association studies. Dean Hamer is best known for these studies. His earliest genetic association studies were about gay men. These were highly criticized some say because the science was faulty. Others say because the subject matter was too controversial. In any case, Hamer has refined his research and he is now studying thrill seeking. While there is no single gene that’s responsible for making a person a thrill seeker, some genetic association studies have identified a candidate gene which seems to play a role. Reporter Kathy Merritt will tell us all about it.

KATHY MERRITT: It seems a little ironic that the search for a thrill seeking gene is happening in a place not exactly known for big thrills, a laboratory. This lab is at the National Institutes of Health in Bethesda, Maryland. And here, under the fluorescent lights amidst the test tubes and computers and stacks of boxes, molecular biologist Dean Hamer has been doing the painstaking work of trying to link behavior and genes.

DH: There obviously are a lot of different factors that guide a person’s behavior, the way you were brought up, where you went to school, who you’ve met, what happened to you yesterday, what happened to you twenty years ago. But we also think that a person’s genes are very important.

KATHY MERRITT: Hamer and a colleague in Israel, Richard Epstein, both began doing studies that tried to link thrill seeking, they call it novelty seeking, with a particular gene. Epstein is director of research at Hertzog Hospital in Jerusalem. He says the study actually began outside the lab with a questionnaire.

RICHARD EPSTEIN: It’s a hundred questions and they answer yes or no to questions like, I enjoy getting up in the morning and doing the same thing at work that I did yesterday. And if you answer yes to that question, you get a low score for novelty seeking.

KATHY MERRITT: Once the answers were tallied, people were rated as high novelty seekers or low novelty seekers. The scientists then gathered DNA samples from their subjects either by scraping a few skin cells off their cheeks or making them swish a saline mouthwash or drawing blood. Then they burst open the cells with a strong detergent, added a chemical to extract the DNA, and purified the DNA using a centrifuge.

[Sound of centrifuge and timer rings]

KATHY MERRITT: But how did they know which gene to look at?

RICHARD EPSTEIN: The particular gene we chose is in a class of genes that are brain receptors for a chemical called dopamine.

KATHY MERRITT: Dopamine is a neurotransmitter. It helps brain cells communicate with each other. And Epstein says previous studies show that it might be involved with impulsive behavior. So, it made sense to study the gene called D4DR. It makes a protein that helps process dopamine. Dean Hamer says they started comparing the gene from one person in the study to the next.

DEAN HAMER: We found there was a difference in that gene. Some people have what’s called a long form of the gene. Other people have a short version of the gene.

KATHY MERRITT: And when they compared the questionnaire results with the genetic differences, the scientists believed they found that people with the long form of the gene had scored higher on novelty seeking than people with the short form. Was this it, then, a gene for novelty seeking?

DEAN HAMER: Of course the gene doesn’t whisper into your ear, “Go bungee jumping.” Genes aren’t that smart or that powerful. The gene just makes a receptor for dopamine. The key point is that people with one form of the gene make a receptor that’s a little bit more sensitive to dopamine. People with the other form of the gene make a receptor that’s a little bit less sensitive to dopamine. Presumably what happens is that when those two people do a new activity like bungee jumping, they release the same amount of dopamine in the brain. But depending on which form of the receptor they have, that either feels good or it feels bad.

KATHY MERRITT: Hamer and Epstein thought they found a connection. But despite their conclusion, there’s a problem with their research. Other scientists have had mixed results in trying to replicate the findings.

AM: In our hands there was no relationship between the dopamine D4 receptor gene and the individuals with high novelty seeking.

KATHY MERRITT: Anil Malhotra is chief of the molecular psychiatry unit at Hillside Hospital in Long Island, New York.

ANIL MALHOTRA: And in fact, in one population of subjects found the opposite association, that the patients were the subjects with the low levels of novelty seeking were linked to this particular form of the gene.

KATHY MERRITT: Malhotra says there are lots of reasons why scientific studies don’t replicate. For one thing, his study used subjects from a different population group. They were all from Finland.

ANIL MALHOTRA: They’re a very special population genetically, meaning that they haven’t interbred for generations and generations with outsiders. The other studies -- one study was a U.S. study, which is a fairly intermixed population. The other study was an Israeli group. So, those are different populations of people, and perhaps these relationships exist in Israel and in the U.S. population studies and not in Fins.

RUTH HUBBARD: There is a basic flaw in all of this research.

KATHY MERRITT: Ruth Hubbard is a retired professor of biology at Harvard and a board member of the Council For Responsible Genetics. She says the human genome is so big and people are so different that you can’t just study one small group of people and say the results apply to everybody.

RUTH HUBBARD: You could, in fact, by focusing on the right thing and structuring the way you wanted to structure it, you could get any result you wanted. You could always come up with a genetic linkage to the trait that you are trying to prove is genetic and inborn, and biological. And then a little more research, or a good deal more research, is going to throw it out.

KATHY MERRITT: Even the scientists doing the research say that genes don’t determine behavior. In fact, Hamer and Epstein say the D4DR gene has only about a five or six percent influence over novelty seeking behavior. As many as ten other genes may play a role. But Epstein says genes can help move people in a particular direction.

RICHARD EPSTEIN: You could have a bank robber who is very flamboyant and very dramatic, and you could have a bank robber who’s uh…very quiet and…and goes about his work in a very undramatic fashion. And similarly you could have a research scientist who can be very dramatic and broadcasts his enthusiasm to everyone, and a research scientist who does things very quietly. The critical issue for society is why one person decides to be a bank robber and another person decides to be a research scientist. The “how’ we decide to do it -- the manner and the style -- is due to genes. But the “what” and the “point” of our behavior and the goals that we set for ourselves are much more influenced by parents, and society, and the culture that we live in.

[Theme music]

KATHY MERRITT: Epstein and Hamer say the next decade will see an explosion of research in behavioral genetics. Their studies are the first of many that will try to tell us just how much of our personality comes from our DNA.

JOHN HOCKENBERRY: Kathy Merritt learned that it may be a long time before we have conclusive results in genetic research. Even so, the work of geneticists like Dean Hamer is often sensationalized in the press. [rustling paper] Let me give you some examples here. Let’s see. Grumpy, fearful, neurotics appear to be short on a gene. That’s the New York Times, November 29, 1996. Here’s another one. Scientists hope cheap date gene defect can be found in humans too. I’d be interested in that. L.A. Times, June 12, 1998. Or how about this? Study provides new evidence of “gay gene”, Washington Post, October 31, 1995.

PILAR OSSORIO: If we call something a “gay gene”, then that can really mislead people into thinking, oh, gay people are so different because they have some gay gene that I don’t have.

JOHN HOCKENBERRY: Dr. Pilar Ossorio.

PILAR OSSORIO: They don’t realize, well, we basically all have the same genes. And so that kind of reporting and that kind of labeling, it is misleading.

JOHN HOCKENBERRY: Jonathon Marks claims that the real culprit isn’t the media but the scientists themselves.

JONOTHAN MARKS: The training of the average geneticist is to learn how to run gels, to learn how to work the equipment that has the flashing multi colored lights, but not to learn the humanistic aspects, the bioethics, the history that defines the work as meaningful, that defines the work as socially relevant. And that scientist who has had technical training no longer has the luxury of denying the social relevance, of denying their own responsibility for the work that they do.

PILAR OSSORIO: There’s no such thing as pure research. And I think it’s especially important for scientists who are doing things like behavioral genetics which is very controversial, which touches on issues such as sexuality, such as violence, such as alcoholism. It touches on issues which are contentious and contested in this society. And so, I think it’s particularly important in those cases for scientists, in order to be able to do good science, to be very very self examining about what our thought patterns, and structures, and preconceptions are. Because if science which is not very good is incorporated into social policy, a lot of people’s lives can be hurt.

JOHN HOCKENBERRY: Jonathon Marks says that happened in the 1920s when there was a great deal of publicity about the influence of genetics.

JONOTHAN MARKS: What geneticists were emphasizing is how important genetics was in American life. What we needed to do was to improve the gene pool of the American people and the most immediate result of that particular social movement led by the scientists was discrimination, was the violation of civil rights, was the restriction of immigration, was the involuntary sterilization of the poor on a very large scale. The tragedy is that this era of genetics is generally not part of the training of the average geneticist and it needs to be.

JOHN HOCKENBERRY: Jonothan Marks is referring to the eugenics movement of the early 1900s. At that time unfounded assumptions about the heritability of character traits led to oppressive social policies in a number of countries. Particularly here in America. Women who were branded as feeble minded, criminal or insane were forcibly sterilized to prevent them from passing these traits on. The argument was that it was inefficient to allow such “problem parents” to produce offspring which the government would then have to support. By 1935, 30 states and Canadian provinces had sterilization laws on the books. Ultimately over 60,000 women were sterilized under these eugenics laws.

[Theme music]

JOHN HOCKENBERRY: That’s our painful past. But what about the future? As our understanding of genetics and personality grows, will we remember the lessons of the past? Do we understand the social impact of our scientific discoveries? And what will we do with that knowledge? Who decides how and whether a person’s personality needs improvement? And who decides what is socially unacceptable behavior? If you are hyperactive, are you also more curious? If you’re a thrill seeker, are you also more liable to break the law? Do we want to cure shyness or disruptive behavior? A seemingly endless quest for knowledge surely must be a genetic trait of the human species. But often our ability to discover how things work races ahead of our ability to consider the implications of our actions. How do we handle the knowledge we’re uncovering? This is a question not only for the scientists but also for the rest of us.

[Theme music]

Credits for The DNA Files:

The DNA Files is produced by SoundVision Productions and is made possible through the generous contributions of the National Science Foundation, the Department of Energy and the Alfred P. Sloan Foundation.

For more information, and for an interactive look at some of the issues behind this program, go to our web site at www.dnafiles.org. For tapes and transcripts of this program and this series, contact VisABILITY at 303.823.8000. To contact The DNA Files, send your email to feedback@dnafiles.org. This program, "DNA and Behavior: Is Our Fate in Our Genes?", was produced by Claire Schoen with reports from Jackie Northam, from WBEZ; Kathy Merritt, from WAMU; Loretta Williams and Robin Marks. The engineer was Robin Wise and the editor was Sora Newman. The DNA Files Executive Producer is Bari Scott. The Project Director is Jude Thilman.

Managing Editors of The DNA Files are Loretta Williams and Catherine Stifter. Production manager is Catherine Gollery. Technical Director is Robin Wise. Adi Gevins is Director of Research and Creative Consultant. Sally Lehrman is Content Consultant. Original music composed and performed by Bill Frisell. Introductory Feature produced by John Rieger and edited by Gary Covino.

This has been a SoundVision production.

This program is distributed by NPR – National Public Radio.

The DNA Files: Unraveling the Mysteries of Genetics

“DNA and Evolution: Where Did We Come From? Where Did We Go?”
Transcript

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For further information about genetics and these programs, as well as the producers who brought you this series, visit the project web site at www.dnafiles.org

Send your questions about genetics and this project to feedback@dnafiles.org

“DNA and Evolution: Where Did We Come From? Where Did We Go?”
Transcript

(Theme music begins)

JOHN HOCKENBERRY: This is The DNA Files, I’m John Hockenberry. Scientists say all life contains the same genetic building blocks and just how we’re related is written in our DNA.

DR. KENNETH KIDD: We can compare the DNA sequence we find in modern humans with that in chmips and gorillas.....and see how similar the DNA sequence is..

JONOTHAN MARKS: There's a cultural assumption here, and that is that the genetic similarity overrides all other kinds of differneces. //// If you can't tell the human from the chimpanzee at twenty paces you're not a very good biologist.

JOHN HOCKENBERRY: What does it mean to be related to chimps, to apes, to each other? Genetics adds new fuel to some old debates about human evolution. Coming up, the Goddess of Memory helps us understand DNA and Evolution: Where did we come from and where did we go?

But First.....

JOHN HOCKENBERRY: The Oscar-winning documentary for 1951 was the tale of four Norwegians and a Swede who crossed the Pacific from Peru to Tahiti on a primitive balsa-wood raft-voluntarily! The voyage of the Kon Tiki was anthropology of the epic school. Thor Heyerdahl and his crew hoped to prove that the people of Polynesia could have come from South America. Alas! scientists believe quite differently today, in part because of a tale told by DNA, as John Rieger reports.

JOHN RIEGER: He was a Norwegian in Polynesia in the 1930s, an adventuress young biologist who rejected the accepted wisdom. Although the Polynesian islands are situated closest to America, it has nevertheless been assumed that these people originally came from the Asiatic fringe, the cradle of the human race. Thor Heyerdahl believed that the first Polynesians must have come west from South America and he set out to prove it.

[music]

On a crude balsa wood raft modeled after the boats of ancient South Americans, Heyerdahl and a crew of four set sail from Peru in 1947, casting his theory’s fate and his own to the Pacific. The voyage of the Kon Tiki was a great adventure and an Academy Award winning documentary. Unfortunately, Heyerdahl was wrong.

PROFESSOR REBECCA CANN: The resounding answer from human genetics is no, Polynesians do not come from South America. They most assuredly come from probably some part of Southeast Asia.

JOHN RIEGER: In the early 1980s Professor Rebecca Cann a molecular biologist at the University of Hawaii began studying a rare genetic mutation, a tiny fragment of DNA that seems to appear in people of Southeast Asian heritage no matter where they live today.

REBECCA CANN: Then when I began working in the Pacific uh we discovered that they were a very high frequency of Tahitians, of Marquesans, of Easter Islanders, of Hawaiians, of Cook Islanders.

[waves crashing in background]

JOHN RIEGER: Here was genetic evidence that Pacific Islanders had come from Southeast Asia, but how, and by what route? In order to figure that out, Cann turned her attention to another bit of DNA known to be hyper variable. This DNA mutates so frequently that each new settlement established during some ancient migration would have its own genetic signature. But to decide which mutations and which settlements came first, Cann would have to look several thousand years into the genetic past.

REBECCA CANN: You try to reconstruct what were the ancestral mutations and which are new ones which have appeared in a certain period of time and are restricted geographically, or ethnically or culturally in some way. If you understand those rules, then you can connect a series of mutations to their ancestral state and keep going back and back and you have a reconstructed ancestor.

JOHN RIEGER: Cann’s DNA evidence suggests that the first Polynesians spread from Southeast Asia. But scientists in other disciplines have questions of their own. How did they cross the sea?

[music]

Thor Heyerdahl believed that the colonizers of the Pacific couldn’t sail into the wind. Wallowing and virtually unsteerable, the Kon Tiki drifted westward from Peru washing ashore after 101 days on an uninhabited island near Tahiti. But today there is evidence that the first Polynesians came eastward in canoes. Linguists have traced the Polynesian vocabulary of canoeing to Asian languages. A rich oral tradition including the songs of the hula speaks tellingly of certain regional flowers, fish and birds. There is one piece that doesn’t fit though, the sweet potato. It’s a staple of the Polynesian diet. It came from South America.

REBECCA CANN: Horticulturists have DNA sequences from the sweet potatoes and they can actually identify that the cultivar is the same germ plasm. In vernacular English that means that it’s the same identical DNA sequence present in South America and present in the Pacific Islands.

JOHN RIEGER: This piece of genetic evidence remains stubbornly undigested. Could the ancient Polynesians have sailed to South America into the wind and then returned bearing yams. Ironically, scientists today are taking a page from Thor Heyerdahl trying to reconstruct the sailing technology that could make such a voyage. Rebecca Cann.

REBECCA CANN: We say as geneticists this is likely but the people who actually attempt to reconstruct how it’s done, they...they are showing us what it might have been to actually experience it historically.

[music]

JOHN RIEGER: So, Thor Heyerdahl’s main theories may have been wrong, but the Kon Tiki did not sail in vain.

I’m John Rieger for The DNA Files.

JOHN HOCKENBERRY: This is The DNA Files, I'm John Hockenberry. Today we're going be asking what DNA can tell us about our origins: about our past as a species, our relation to all
other forms of life, our history.

And so, that's why I went to the computer store just now and brought back this CD-ROM here. It's a new software program called Mnemnosyne 99. Mnemnosyne was the Greek goddess of memory, I believe. Anyway this is supposed to be a fantastic program. It's got all the latest genetics and physics and biology and - well, let's just stick it in the computer and fire it up…right, here it comes...

MEMNOSYNE: Greetings, bipedal human consumer genetically related to a chimpanzee. It's a pleasure to meet you.

JOHN HOCKENBERRY: Why don’t you just call me John?

MNEMNOSYNE: Certainly. And, you may call me "Mnemnosyne 99".

JOHN HOCKENBERRY: Okay, listen...I want to ask you something. I want to ask you about human origins. You know, where do we come from? How did we get here?

MNEMNOSYNE: Origins, indeed. I can do that. Where would you like to start?

JOHN HOCKENBERRY: How about at the beginning?

MNEMNOSYNE: Excellent choice. Puts things in perspective. Let me back up here... hang on.... rewinding billions of years, is not as easy as you think.

JOHN HOCKENBERRY: Take your time.

MNEMNOSYNE: Okay, I'm ready now. I'm at the beginning of the cosmos.

JOHN HOCKENBERRY: Great. So what can you tell us about the beginning?

MNEMNOSYNE: ... Nothing.

JOHN HOCKENBERRY: Nothing? Nothing? That's it? Are you sure I installed you correctly?

MNEMNOSYNE: No I mean there is nothing. There's nothing here. No time, no space....

JOHN HOCKENBERRY: I can't see anything.

MNEMNOSYNE: Well, of course you don't. That's why they call it nothing.

JOHN HOCKENBERRY: Seems boring. How long does this go on?

MNEMNOSYNE: Well, that’s hard to say, John. Remember there's no time here. Of course, thank goodness, there is just a little something , a little ...abstract... something, even if you can't see it.

JOHN HOCKENBERRY: What would that be?

MNEMNOSYNE: The laws of physics. The laws are here, John, and according to the rules of
quantum physics, when you have nothing, you have a vacuum in which anything can happen. Anything.

JOHN HOCKENBERRY: So?

MNEMNOSYNE: So all of sudden, it does: it just happens.

JOHN HOCKENBERRY: Wow, look at that. That's the big bang isn't it?

MNEMNOSYNE: Yes. And you hear that? That's the clock. Time has begun. The universe is expanding. There's a lot going on. One-hundredth of a second after the big bang: electrons and
anti-electrons are forming. One second: neutrons and protons stabilize. They’re the building blocks of matter. And seven hundred thousand years: matter separates from light, helium and hydrogen atoms appear. And then, in two million years, the stars and galaxies are forming out of the helium and the hydrogen.

JOHN HOCKENBERRY: This is good, this is good, here comes the milky way, and now the sun, and then the solar system, asteroids smashing together to form the planets, could we just fast forward a bit, and get up to the origins of life part...

MNEMNOSYNE: Well, of course. Hang on. Just a second and here we are: planet earth-- about 4 and a half billion years ago.

JOHN HOCKENBERRY: Hmm. Gases, fog. It looks kind of murky out there.

MNEMNOSYNE: Well, John, I'm only a computer program, all I can show you is the data the scientists gave me. Maybe you'd like to meet some scientists? I've got a clip I can run.

JOHN HOCKENBERRY: Sure. You know, now that I think about it, I'm not even sure what life
is.

MNEMNOSYNE: Well, no one's too sure. It's more basic than being able to think, or to move, or breath. One thing everybody seems to agree on is that all life has the ability to reproduce itself. Here, take a look at this:

ALAN WEINER: My name's Alan Weiner, I teach molecular biophysics and biochemistry at Yale University

NANCY MAISELS: I'm Nancy Maisels. I teach molecular biophysics and biochemistry and genetics at Yale. I think life is something that's replicating itself in an informational way. So rocks aren't life, because you need something to make a rock, and then it's just a rock. But a cell that divides is life or a virus that can replicate itself is life.

ALAN WEINER: And the essence of replication and life in the living system is that there is enough information there that the mistakes you make can produce more interesting molecules which will also be capable of self-replication.

NANCY MAISELS: When we say "life" it has a meaning, and it strikes our souls, and there’s got to be some kind of a mystery about. Now, maybe we're being counter-productive in what we think about, because if we solve the mystery then it won't be there anymore. But I think most of us have a gut feeling of whether something is alive or not, and maybe that is even a test for being alive oneself.

JOHN HOCKENBERRY: Hmm..... you know it's interesting to think that being able to make
mistakes is essential to life.

MNEMNOSYNE: I never make mistakes, John.

JOHN HOCKENBERRY: You're not supposed to. But if a mistake did happen—a mutation- while you were replicating yourself—then that would be evolution, wouldn’t it? That's how it works with us anyway: our blueprint, our DNA, makes copies of itself from one generation to the next, and in the process, errors occur. Each generation is a bit different from the one that came before.

MNEMNOSYNE: And in each generation, some of your mistakes turn out to be bad ideas. They don't work. So, nature wipes them out. But once in a while the mutation is a good one; it accidentally gives you a faster brain or a longer beak or maybe a few extra legs, some kind of advantage. And then, gradually, over many generations, it spreads. So you're right, John, that's evolution.

JOHN HOCKENBERRY: But how did it get started in the first place? I mean, where did DNA come from?

MNEMNOSYNE: Well, chemists think that if you could recreate the conditions of the
earth about four and a half billion years ago -say, the climate, the oceans, the atmosphere- you'd see it happen spontaneously. You'd just see DNA, or more likely a molecule that's an ancestor of DNA, it would just pop out of the mix.

JOHN HOCKENBERRY: Can they do that in a laboratory?

MNEMNOSYNE: Well, no. Actually, they've tried, but so far they can't seem to pull it off. In fact chemists have a little joke about that, you know: they say that life is impossible. Experience shows that it can't happen. That we're just imagining it. Hahahaha....

JOHN HOCKENBERRY: Right. Those…those chemists. Anyway, could we move along, get out of this murky, foggy part? Can you fast-forward and take us to a the place where the light's a little better? What I remember from high school is the part where we—I mean, we humans—begin to diverge from the apes.

MNEMNOSYNE: Okay let's see...hominids, origin of hominids, say five million years ago, give or take....

JOHN HOCKENBERRY: You know, I was always sort of confused by the family tree idea. I mean, there's chimpanzees and gorillas and monkeys and orangutans, and it seemed like scientists were always arguing about who was related to whom. Can DNA help us straighten things out?

MNEMNOSYNE: Oh yeah. You bet. Here, I've got an expert for you: meet Dr. Kenneth Kidd, Professor of Genetics and Psychiatry at Yale University.

KENNETH KIDD ONE: We can compare the DNA sequence we find in modern humans with that in chimpanzees and gorillas and orangutans and old world monkeys.....and see how similar the DNA sequence is. And indeed the sequences differ at about 2 to 3 percent between humans and
chimpanzees and gorillas and much more with everything else. Classical taxonomists had said chimps and gorillas were very close to each other and distant to humans. If anything, the evidence is that humans are more closely related to chimpanzees. So that's been something new coming out of DNA. Some people have not been pleased by that, but there's always a little pleasure in being iconoclastic and finding something new and upsetting the tradition.

JOHN HOCKENBERRY: You know, I hear a lot of genetic percentage numbers these days:
people say our genes are 98 percent the same as a chimpanzee's, 70 percent the same as yeast. I've heard we're 30 percent the same as a day lily. The numbers are surprising at first. I start to get a warm glow, a feeling of kinship; life is just one big family; and then I think – wait a minute, all life on earth comes from some original bit of genetic material, doesn't it? Naturally we have common ancestors – people, chimps, bananas, scorpions....so maybe the numbers aren't surprising at all. Maybe they're exactly what we should expect. I'm not sure I know what they mean though. Do you?

MNEMNOSYNE: I'm a computer, John. Meaning is not my strong suit.

JOHN HOCKENBERRY: Right.

MNEMNOSYNE: Warm feelings would also be ruled out. But let me see, I’m sure I’ve got a file around here on philosophy, and ethics, and stuff like that. So, here, try this: here's Jonathan Marks.
He's a biological anthropologist at the University of California at Berkeley.

JONATHAN MARKS: There's a cultural assumption here, and that is that the genetic similarity overrides all other kinds of differences. If you compare a human and a chimpanzee and a gorilla, you find all kinds of differences. You find the difference between the human and chimpanzee behaviorally, physically, demographically, ecologically, mentally. Diagnosibly different in all those ways. The only way you can't tell them apart readily is genetically. Well what does that tell you? You can look at any part of their body and tell them apart. If you can't tell the human from the chimpanzee at twenty paces, you're not a very good biologist. That's the bottom line.

JOHN HOCKENBERRY: Well, now I'm not sure I know what to make of-- Excuse me. What's that music?

MNEMNOSYNE: It's supposed to be African music, John. But unfortunately, I don't have enough memory to do it right. So, it was just supposed to make you think of Africa, and remind you of your next question.

JOHN HOCKENBERRY: And that would be?

MNEMNOSYNE: Well, if modern humans split from chimps and gorillas a while back - say, between 6 and 8 million years ago, then the question is, where? Where on earth did it happen?

JOHN HOCKENBERRY: The music is supposed to be a clue?

MNEMNOSYNE: Well, Actually it's DNA that's the clue. You remember we were saying that mutations occur within DNA over time –genetic mutations. you can think of this as variations on the original sequence of genes.

JOHN HOCKENBERRY: Genetic variations, right.

MNEMNOSYNE: Right. Well, it turns out that some groups of people have more genetic variation than others do.

JOHN HOCKENBERRY: Really?

MNEMNOSYNE: Yeah, really. On the whole, people who live in Africa have more of this "genetic variation" than people who live in Europe or the Americas or anywhere else.

JOHN HOCKENBERRY: Why is that?

MNEMNOSYNE: Well, a lot of scientists think that it's because modern humans--'Homo sapien sapiens"- developed in Africa first. This is called the "Out-of-Africa” hypothesis. Let's go to Dr. Kidd to explain:

KENNETH KIDD: Modern humans arose in Africa and have existed in Africa for a long time: two
hundred, three hundred thousand years at least. And in that period of time a lot of variation has accumulated, and most African populations have most of that variation. We find less variation once we get immediately outside of Africa. And it's that somewhat reduced amount of variation that we then see all around the rest of the world.

So our interpretation is that about a hundred thousand years ago a relatively small group of modern humans left Africa and took with them really only a subset of the genetic variation that pre-existed in Africa.

JOHN HOCKENBERRY: So- let's see- the idea is that a small number of people migrated
out of Africa; and because they were just a small group, they didn't have as much genetic variation as the larger group who stayed behind in Africa. These immigrants settled in Europe, and Asia, and all around the world. But to this day, their descendants still have less genetic variation than Africans. That makes sense. You know, I've heard that we're descended from just one woman back in Africa, too: African Eve, isn't that how the story goes?

MNEMNOSYNE: Not exactly. Maybe I better explain. And again, it has to do with DNA. But this time it's not the regular DNA you find in the nucleus of your cells. It's a special kind of DNA outside the nucleus; it's called "mitochondrial DNA." You inherit your mitochondrial DNA only from your mom, your mother. Everyone has it but only women pass it along. So, naturally when scientists look at these particular genes and try to track them back in time, the line leads to-

JOHN HOCKENBERRY: - to a woman. Of course. And when people call her "Eve," does
that mean she's the mother of us all?

MNEMNOSYNE: Well, now you're embellishing the story. Maybe you should hear it from
one of authors, not from me. So, let’s go to Dr. Mary-Claire King. She's a geneticist at the University of Washington:

MARY-CLAIRE KING: It goes like this: At some time in the evolution of people, there was one
mitochondrial sequence that was the ancestor of all subsequent mitochondrial sequences. One can estimate the time and place at which that sequence occurred. As it happens, the best estimates of the ancestry of mitochondrial sequence are that the original sequence was in an individual who lived in Africa about 150,000 years ago. Now, that means that and absolutely no more. It was certainly not the only person living in Africa 150,000 years ago. It was not our only "ancestor" and that individual may have contributed nothing to any of our other genes.

JOHN HOCKENBERRY: Well at least we've got the big picture, right? The main thing is modern
humans developed in Africa and then, about 150,000 years ago they began spreading around the world and -- pardon me, what's that noise? Are you not feeling well?

MNEMNOSYNE: Oh, it just means I have a conflict in the data banks. It happens all the time.

JOHN HOCKENBERRY: What’s the conflict?

MNEMNOSYNE: I hate conflict, don't you? But well, - let's face it. The out-of- Africa story is the one most scientists tell. But there is a minority viewpoint. Let me introduce you to Dr. Milfred Wolpoff.

MILFRED WOLPOFF: I am a Professor of Anthropology at the University of Michigan. My specialty is paleoanthropolgy. I'm a paleoanthropologist. I'll study anything that doesn't smell or talk back.

JOHN HOCKENBERRY: So what's the conflict here? What's Wolpoff’s problem?

MNEMNOSYNE: Well, when you use DNA to explore the past, what you hope is that your genetic evidence will fit nicely with other bits of evidence you may turn up whether that's bones or archeology or whatever. DNA and the fossil bones that paleontologists dig up should be saying the same thing; they should tell the same story. But Wolpoff thinks they don't.

MILFRED WOLPOFF: If you thought, as a paleontologist, that everybody descended from Africans, what you might expect to do is to go to different regions of the world, find the first modern humans, and say, aha, I've studied these people and they look like Africans, and this shows that all modern people came from Africa. But that isn't the evidence that was there at all. The Fossil people squabble with each other all the time. They fight like cats and dogs, and they do it in public on radio shows and in front of the TV cameras and everyplace else, which leads to what I like to call the “yes-it-is-no-it-isn't” argument: “Yes WLH-50 is a modern human,” “No is isn't,” “Yes it is,” “No it isn't,” “Yes it is” “Well I studied it and it is.” These don't get anywhere.

JOHN HOCKENBERRY: But what am I supposed to think when scientists argue with each other? They're the experts, why don't they just get it right?

MNEMNOSYNE: Oh, John, please. This happens all the time. If your memory was as long as mine--do you have any idea how long it took scientists to agree that the earth was flat?

JOHN HOCKENBERRY: Maybe round?

MNEMNOSYNE: Or whatever. The point is, Wolpoff has a story of his own. He calls it
"multi-regionalism." He thinks people began to leave Africa a very long time ago, millions of years ago, and then they evolved in many different regions of the world.

MILFRED WOLPOFF: We can see this clearly in the fossil record, it's part of what multi-regional evolution is about. Some of the features that characterize living people seem to be there for a long time, and in some cases back to the earliest time of the habitation. Asians have always had flat faces, as they do today. Their cheeks are forward, and their facial area is flattened, and their noses don't project all that much. This isn't true of every Asian, of course not. But it characterizes an awful lot of Asians in general, and it's there in the very earliest fossils in the region.

JOHN HOCKENBERRY: All right, I like that story almost as well much as I like the out-of-Africa
one. It does remind me of something, though. I can't quite put my finger on it-

MNEMNOSYNE: Well, there is an old story about human evolution which you might have
heard. The story's discredited now, but it used to be common; it claimed that humans were divided into different races, almost like different species. The races were different because they had different origins, different lines of evolution.

MILFRED WOLPOFF: And their take on human evolution was that some races evolved further than others. You can imagine which ones evolved all the way, right? And then, you can imagine which ones didn’t evolve very far at all. And so it was, look, this was a justification of the Holocaust. It wasn't just a way of being mean, it was a way of the Germans ridding the human race- i.e., the Germans- of all the bad genes that were causing Germans to do bad things. That is the Jews, and the gypsies and black Africans and anyone else who hadn't evolved as far. And this stuff was part of the normal scientific literature. This was not a couple of nut cases at the fringes of science just writing popular articles and stirring up the masses. By and large what I'm saying was widely believed. It was part of your biological education.

JOHN HOCKENBERRY: I always thought it was strange the way people try to distinguish the "races." Usually they start sorting by color, don't they, so they come up with white, black, sometimes yellow, maybe red. But it turns out that's never enough, because how can tall blonde Swedes and short dark Italians be in the same race, so they keep sub-dividing and inventing new races.

MNEMNOSYNE: Well, that’s true and you're allowed to divide humans into racial groups if you want, John: you can have four, five, ten, twenty, you can have as many as you like. It's arbitrary. But then if you look at these groups genetically, if you try to compare their DNA, you discover that the differences between them are tiny. The differences inside each group are much larger. It's like trying to compare football teams, if you know what I mean. So, wait- here's Dr. Hank Greely, a law professor at Stanford University and he’s associated with genetic research projects.

HANK GREELY: Most genetic variation in humans occurs within groups and not between groups.
If you think about the National Football League: the average height and weight of the San Francisco 49ers team probably is very similar to the average height and weight of the Dallas Cowboys team. Within each of those teams, though, you'll go from a defensive lineman at 6 foot 10, 330 pounds, to a place-kicker at 5 foot 4, 140. The variation within the team is enormous, the average variation between the teams is quite small. The same is true of human genetics.

MNEMNOSYNE: It’s a shame we can't group human beings on the basis of their operating systems: like DOS, Unix, MacIntosh. It would be so clean, so simple--

JOHN HOCKENBERRY: --so human, so arbitrary. But listen, excuse me, is there some way you could turn your clock down? Nothing personal, but-- the perpetual ticking in the background, doesn't it get on your nerves after a while?

MNEMNOSYNE: I’m sorry, John. That's the cosmic clock. That’s the one that started with
the big bang 12 billion years ago. It's always running in the background. You do know the big bang isn't over? It keeps right on going. The universe is expanding while you’re sitting there.

JOHN HOCKENBERRY: I never noticed that.

MNEMNOSYNE: Well, you will one of these days, believe me. But for now let's go back to the little picture, the human story. Where were we?

JOHN HOCKENBERRY: Let's see: somehow people left Africa and began moving around the world. And then what? What can our genes can tell us about our past that we wouldn't know otherwise?

MNEMNOSYNE: Well, quite a bit. They can help us figure out what people did once they got where they were going. In fact there are huge questions no one could ever answer without help from DNA. For example, the spread of agriculture.

JOHN HOCKENBERRY: What's that on your screen now? Is it…is it…is that a map of the Middle East?

MNEMNOSYNE: Exactly. It’s not the only place where agriculture began, but it’s where scientists have the most data.

JOHN HOCKENBERRY: Okay.

MNEMNOSYNE: So you see the green areas on the map?

JOHN HOCKENBERRY: Yes, that's farmland, right?

MNEMNOSYNE: Yes, that’s the birth of agriculture. It was not some trivial event, you know. It was a very big deal.

LUCA CAVALLI-SFORZA: Agriculture was a very major crisis, if you want, in humanity in the sense that it brought about completely new things, problems, wealths. So, it was a time of change which happened about ten thousand years ago. This is what archeologists tell us. And what is very remarkable is it happened almost at the same time in three or four parts of the world; the Middle East, where two plants essentially were domesticated, wheat and barley. In addition, in the Middle East it was possible to domesticate a number of animals, which included cattle, and goats, and sheep, and pigs- so that there was a mixed economy of animals and plants domesticated.

MNEMNOSYNE: That's Dr. Luca Cavalli-Sforza. He’s a geneticist at Stanford University and he has a famous theory about agriculture. It involves human genes. And we'll get back to him in a minute. But right now, watch what happens when I run the agriculture program. Look at the screen. Watch the green areas.

JOHN HOCKENBERRY: Hmmm. Oh that the green is beginning to spread. Looks like it's moving north-heading to Europe. At first it's just around the Mediterranean. Then.... it begins to move up the big rivers, like the Danube there into Germany... and it keeps spreading north, till.... finally it gets to Scandinavia. And then it's pretty much green all over Europe.

MNEMNOSYNE: So it is. This picture is based on archeological evidence. There's lots of that, you know: seeds, tools, bones. It’s fairly well known. But now: can you see what's wrong with this picture? Perhaps maybe wrong is the wrong word, but mysterious? Can you see what the picture's hiding?

JOHN HOCKENBERRY: It looks…it looks okay to me. I mean it says what I've always heard. Hmm.....let's see, I'm looking at agriculture moving from the Middle East to Europe.... but....hang on....am I seeing the spread of a technique, which would be hunters and gatherers learning from their neighbors how to clear land and plant crops and all that...or...

MNEMNOSYNE: Or?

JOHN HOCKENBERRY: Or am I seeing the spread of people, new people coming in from the Middle East, bringing agriculture with them?

MNEMNOSYNE: Exactly. That is the question that stumped scientists. So what's the answer?

JOHN HOCKENBERRY: You know, looking at the map, I can't tell.

MNEMNOSYNE: Neither could Dr. Cavalli-Sforza. Neither could anyone. But he and his colleagues decided to go back to the data and make a new map. The new one shows the same thing; if I ran it again you'd still see the green area moving from the Middle East through Europe. But this time they asked a particular question. They asked: how fast does it move?

LUCA CAVALLI-SFORZA: We made a map by computer of the first time at which agriculture arrived in Europe and agriculture was really wheat. So there were many radiocarbon data already in the literature that told us when wheat was first found. And it was quite clear that there was a very gradual and very slow spread. After the beginning, which was about ten thousand years ago, the first arrival of agriculture to the extreme north of Europe was four thousand years later. Which is about four thousand kilometers in…as the crow flies. So it's easy to say, four thousand kilometers in four thousand years, it’s one kilometer a year. That was slow, I think. And one possible reason why it was slow was that what really spread was not the technology but were the people themselves, the farmers. Because the farmers certainly take time to multiply.

MNEMNOSYNE: Now, history shows that technologies can move fast. Pottery, for example: let’s look at pottery. It starts in the Middle East later than agriculture, but it pops up, but it pops up in Europe almost immediately. Or nowadays, think of the rapid spread of a really good computer program like, well, like me for example.

JOHN HOCKENBERRY: That's a good idea. But…but it’s just a clue, isn't it? It doesn't prove
anything. So, to settle this question, we’re going to need a new kind of evidence. I mean we need something that’s not seeds, or plows, or…or hang on a minute. What about DNA?

MNEMNOSYNE: Now, why do you say that?

JOHN HOCKENBERRY: Well, if there really were new people moving in from the Middle East,
settling down and raising kids, they'd have to bring their genes with them, right. Of course they would. So perhaps we could find genetic patterns that start in the Middle East and spread.....oh but wait. Where would we find that evidence now? Genes don't hang around buried in the dirt like shards of pottery.

MNEMNOSYNE: No. No. No, they don’t. They hang around in the children. So if our hunch is correct, the people born in Europe today would be descendants of settlers who started out in the Middle East.

JOHN HOCKENBERRY: So, the evidence isn't buried at all. It's right there in the cells of
living people.

MNEMNOSYNE: Yes! (blare of trumpets) Ahem, sorry. I like to play the trumpets when somebody finally gets it.

JOHN HOCKENBERRY: Cute.

MNEMNOSYNE: Of course Dr. Cavalli-Sforza was way ahead of you. He figured that if people could make maps showing the spread of wheat or pottery, then, why not make maps that showed the spread of genes. And that's exactly what he did.

LUCA CAVALLI-SFORZA: We can see in the genetic map of Europe, that there are some genes which differed greatly between the Middle East and Western Europe. And those genes show almost unequivocally that there was a spread of farmers. And there is a kind of center of origin in the Middle East.

JOHN HOCKENBERRY: That's pretty neat. Let’s take a short break.

(music break)

JOHN HOCKENBERRY: This is The DNA Files. I’m John Hockenberry. We learn a lot when we combine genetic history with other kinds of history. But what if we have only a gene map? That would show us something happened back then - people moved from here to there- but…but why? What were they doing? I mean we wouldn't know that, would we?

MNEMNOSYNE: Well, of course not. It's the eternal complaint of scientists. We always need more data. We need more fossils, more cave paintings, more ancient cities. More DNA. And of course, we need more money for the research.

JOHN HOCKENBERRY: Right.

MNEMNOSYNE: Well, that leads us to an interesting story: there's a controversy in the world of genetic research these days. It's not an especially pretty story, but it could tell you a lot about the way science happens- or fails to happen --in the real world or the way it doesn’t happen. Would you want to hear that story?

JOHN HOCKENBERRY: Sure.

MNEMNOSYNE: Okay. It goes like this: As you may have noticed, John, my data banks contain more information from Western Europe and North America than they do from say Pago-Pago or the Malay Archipelago.

JOHN HOCKENBERRY: Well, I know that's why we looked to Europe for the spread of agriculture, rather than China or South America.

MNEMNOSYNE: Of course. Most scientists prefer to do the research in their own back yard. It's expensive for them to mount an expedition to Mongolia or the Amazon. But when you want to study the genetics of human populations, you notice that some groups are being left out.

JOHN HOCKENBERRY: Naturally.

MNEMNOSYNE: That's why, some years ago, Dr. Cavalli-Sforza and other scientists called
for a new research project: they named it The Human Genome Diversity Project.

JOHN HOCKENBERRY: Like the Human Genome Project? I've definitely heard of that.

MNEMNOSYNE: Well, you could think of it as a parallel. You know that the Human Genome Project- with a lot of government funding- is trying to map all the genes in human DNA. And this will be valuable to know, but of course no actual human being has all the possible human genes. Some people have blue eyes, some have green eyes, some have black hair, some have blonde hair

JOHN HOCKENBERRY: Yeah. Yeah. I’ve noticed.

MNEMNOSYNE: Yeah, so on and on. In the same way, different groups of people- Mongolians, Zulus, different populations- they all have different variations of the common gene pool. Population geneticists like to study the variations.

JOHN HOCKENBERRY: Let's see......why don't you give me an example....

MNEMNOSYNE: Well, Okay. I'll try. Let’s see now, you've heard of blood groups, right? Blood groups.

JOHN HOCKENBERRY: You mean like A, B, O...that business?

MNEMNOSYNE: That’s right. Right. And there's another blood group called Rh. If you have the Rh gene, you're Rh positive.

JOHN HOCKENBERRY: Right.

MNEMNOSYNE: Yeah. Okay. If not, we say you're Rh negative.

JOHN HOCKENBERRY: Okay.

MNEMNOSYNE: Now looking around Europe you find that most people are positive. Only about 15 percent turn out to be RH negative. And this is true everywhere except when you get to the Basques.

JOHN HOCKENBERRY: The Basques are a group of people living in the north of Spain, up in the Pyrennes and over the border into France. I know they have a very different language from everybody else too.

MNEMNOSYNE: Right. Right. Plus, about 30 percent of them have Rh negative blood. That's a much higher percentage than usual.

JOHN HOCKENBERRY: So if I had Rh negative blood, would it mean I'm Basque or that I have Basque ancestors?

MNEMNOSYNE: Oh no. It wouldn't mean anything. But if you lived in a small town somewhere and 30 percent of the town turned up RH negative, then I might wonder that there was some maybe Basque ancestry there.

JOHN HOCKENBERRY: I see....

MNEMNOSYNE: It's a question of statistics. There's no special gene that would make you Basque or Zulu or Swedish or anything else. But different groups of people can have different distributions of genes: the same genes as other groups, but in different frequencies.

JOHN HOCKENBERRY: Right, I understand.

MNEMNOSYNE: Okay. So this was the idea of the Human Genome Diversity Project. The
HGDP, for short. Cavalli- Sforza and his colleagues wanted to collect genes from people all over the world who they felt were being overlooked.

JOHN HOCKENBERRY: Faraway people – faraway from the point of view of scientists in
London or Paris, anyway – indigenous peoples living in rain forests and so on...

MNEMNOSYNE: Exactly. That’s exactly right. And if Cavalli-Sforza and his colleagues had those data, they could make real world-wide gene maps, and those maps could tell us about human history and migrations. But, believe it or not, this proposal stirred up a ferocious controversy.

LUCA CAVALLI-SFORZA: Indigenous peoples are about the most interesting ones from point of view of study the origin of humanity because they have been isolated for a longer time. And we have since had considerable difficulties because pharmaceutical firms began to be very interested in patenting DNA from all sorts of people including these isolated populations that we would be especially interested in studying. So, there came a lot of problems on the questions of intellectual property and DNA property and so on. There are also people who are scared by genetics in general, and we have had to fight an enormous amount of misunderstanding that has been generated by a lot of more or less well-intentioned organizations; some definitely not well-intentioned.

JOHN HOCKENBERRY: Let me see. What's the problem here? I have heard that private
companies have been poking around the world hoping to find a rare gene here or there that might have some medical use, some commercial value. That could be confused with the Human Genome Diversity Project, now couldn't it?

MNEMNOSYNE: Well, yes it could. And there's another problem: for ethical reasons you need informed consent from the people you do research on. This means that people need to understand the purpose of a research project. That way they can decide whether they want to take part in it or not. But, you could ask, how would you get that consent from a tribe of hunters in a jungle say in Brazil who've never heard of DNA? And sometimes there can be religious conflicts too. For example, listen to Dr. Frank Dukapoo, a Northern Arizona University scientist. He’s also a geneticist, and a Hopi:

FRANK DUKAPOO: All the evidence, data seem to indicate that we came out of Africa. Well, that's what Western scientists; that’s what they think, but the Indians have their own origin myths. Hopis believe we come from a certain place, the Sapofonee (phonetic), for example. So we have our own origin myths. We don't care what the research is. It's just not one of our priorities. We have our own, and we're satisfied with it, and that’s what we believe. I think if we could turn the tables, and say, what if I as an Indian geneticist want to study the blood off Turin, the blood off the Shroud of Turin, I’m sure that a lot of people would object to that kind of research. But unless we put it in those kinds of terms to white people, they just don’t understand why you are so sensitive about this kind of research.

JOHN HOCKENBERRY: I guess if you a have a religious objection to a particular line of research, there's no way to patch things over. It's a problem outside the realm of science.

MNEMNOSYNE: Yes, but even from inside the science, Duckapoo has doubts. The HGDP more
or less assumes that an indigenous group - an ethnic group- amounts to the same thing as a genetic population. Duckapoo points out that this isn't always the case.

FRANK DUCKAPOO: My father was Hopi. He’s Hopi, Ute, and Navaho. So, he's a mixture. And I look at my mother’s side. She is Laguna, she’s Yakima, she’s Uni and part Spanish. So we're all mixed. And those tribes did mix and they did intentionally sometimes when they raided and kidnapped for their members down and they wanted to keep the tribe doing, so many tribes have this add mixture history. And I suspect many of the other ethnics have this kind of history too. The Hispanics might have it, other Indian tribes, and blacks certainly have it. And so, it raises a question, what value is diversity research?

JOHN HOCKENBERRY: Hmmm.... what have you got on the screen now? I can see it's some kind of college campus.

MNEMNOSYNE: This is Stanford University in California. The woman you see walking up is Johanna Mountain. She is an Assistant Professor of Anthropology, and she's about to leave on a trip to Tanzania. She hopes she's going to do genetic research when she gets there.

JOHANNA MOUNTAIN: It's going to be an incredible challenge to convince people that they should participate in this project, and I may be completely unsuccessful. I have to go there knowing that that’s a possibility. I'm hoping this year at least I can develop some trust. And maybe I'll have to go back next year or the year after to actually to collect DNA samples. But I'll take small brushes I can use to collect cheek cells, and DNA can be extracted from those cheek cells. The individual, him or herself, takes a brush and brushes the inside of each cheek three or four times, and then turns the brush to a small tube, and then I bring that back home and extract the DNA at that point. So it's fairly simple. And I don't feel too coercive if the individual is actually doing the sampling himself or herself.

JOHN HOCKENBERRY: What exactly is she hoping to learn when she gets over there?

MNEMNOSYNE: Well, she's studying groups of people in Tanzania and they speak some unusual
languages. She wants to find out if people who speak the same language really have the same genes.

JOHN HOCKENBERRY: Gee, I could think of a problem right away. I mean I speak English but
I wouldn't call myself an Englishman. And you're speaking English right now and you're not even human.

MNEMNOSYNE: Oh, please, John--there are exceptions to every rule.

JOHN HOCKENBERRY: Well, I know it doesn't apply to you. And I know English is a special
case because so many Americans picked it up as a second language when they immigrated . Still, how do you pin down anyone's cultural group? Is it just whatever the person says? I mean, I might tell you I'm a New Yorker because I live in New York right now. But if I was traveling in Europe I might say I was an "American." You know, in Papua New Guinea I might be "a Westerner. " And of course when I go to the nightclubs, I'm really cool and excellent. You know it all depends. It all depends on the circumstances, and I can decide what the circumstances are.

JOHANNA MOUNTAIN: Myself sometimes I would call myself English because that's where I was born. But really I’m culturally an American. So, I completely agree that people may have even more than one label for themselves. And so, what do we do when we’re trying to infer human history? We most generally label people by the language that they speak and hope that that language...that language has been inherited almost like genes, and that the language in a sense has been handed down through history, and that maybe language is a good way to think about
a population.

MNEMNOSYNE: John, while we're talking about genes and languages let's pay a quick visit
to Dr. Joseph Greenberg.

JOHN HOCKENBERRY: Okay.

MNEMNOSYNE: Now, he's a linguist and anthropologist at Stanford. And he's
been working on a riddle scientists would love to know the answer to: and that is how was the American continent settled? He has a theory that people call the Greenberg hypothesis.

JOHN HOCKENBERRY: Great name. We're not talking about the last few centuries, now, when people were sailing here from Spain and England and so on; we have written records for that. I mean I suppose we're asking about a long time ago, when the very first settlers came.

MNEMNOSYNE: Exactly. That’s what we’re asking.

JOHN HOCKENBERRY: I thought there was supposed to have been a land bridge between Siberia and North American during the last ice age. The idea is that people walked over from Asia.

MNEMNOSYNE: Well, that idea fits pretty well with fossil evidence. But if you looked at Native Americans today, you would think that they were the descendants from the first settlers. Could you guess how many migrations there were? Could you guess how many times people crossed the land bridge from Asia? One time? Ten times ? A hundred?

JOHN HOCKENBERRY: Hmm...But how on earth could I tell?

MNEMNOSYNE: Do you want a clue?

JOHN HOCKENBERRY: Okay.

MNEMNOSYNE: How about this…

JOHN HOCKENBERRY: Okay.

MNEMNOSYNE: How many languages do Native Americans speak today?

JOHN HOCKENBERRY: As far as I know they speak hundreds of different languages. I don't
see how that helps.

MNEMNOSYNE: Well that’s true. But when Greenberg-as a linguist,- analyzes the different tongues, he finds they break down into just three families.

JOSEPH GREENBERG: The Eskimo and the inhabitants of the Aleutian Islands speak a group of language we call Eskimo-Aleut. And their closest relatives are in Siberia. The second group are called Nadene. These are a number of very small languages, but the most important languages here are spoken in the Northwest part of the Americas like the interior of Alaska. And these people are called Athabascan. The third group is just all the rest.

JOHN HOCKENBERRY: So three languages, three groups of people, three migrations?

MNEMNOSYNE: Exactly.

JOHN HOCKENBERRY: But... suppose there had been ten groups of people who walked over
the land bridge and then their languages merged later on?

MNEMNOSYNE: Aha. You remember we said that when you do history you hope that different types of evidence will all fit together? Linguistic clues, the fossil record, genetic data?

JOHN HOCKENBERRY: Corroborating data.

MNEMNOSYNE: Exactly.

JOHN HOCKENBERRY: Yeah.

JOSEPH GREENBERG: It turned out that Professor Cavalli-Sforza, on the basis of population
genetics, arrived at precisely the same conclusion that I did. And in fact, an expert on fossil teeth came to exactly the same conclusion: that there were three groups and they coincided very closely with Eskimo-Aleut, Athabascan, and then finally the third and major group, Amerind. Now more recently, people have been, of course, studying DNA and have come to the conclusion that the
three major groups that I distinguished can also be distinguished by separate lines of mitochondrial DNA.

JOHN HOCKENBERRY: Then.... we could just as well have started with genetic evidence
for the Americas, couldn't we?

MNEMNOSYNE: Well, yes we could. But when you're in a search for the past, you can start wherever you like. The main thing is to use all of the available lines of evidence.

JOHN HOCKENBERRY: I wonder, could you use DNA to look into the future as well? In this last
hour you've taken us back a few hundred thousand years. What could the genes say about the next hundred thousand coming up?

MNEMNOSYNE: Hmm...That's a really good question John. I'm checking my data.....but everything I'm running into isn't labeled "data" or "evidence" or any good scientific thing. It all seems to be labeled "common sense"........ what on earth is common sense?

JOHN HOCKENBERRY: Well…well, what would that be?

MNEMNOSYNE: Well, here it says that people are traveling around the planet more and more, intermarrying more. So you might think that isolated populations with unusual distributions of genes will disappear in the long run. Eventually we'll all be more and more alike. Also, as a matter of principle, remember that human evolution hasn't come to a stop. Like the cosmic clock, it goes right on ticking.

JOHN HOCKENBERRY: Right on ticking. Meaning?

MNEMNOSYNE: Well, meaning there might be big event in the future, say a change in climate, a wide-spread disease, who knows what kind of a big event, but one that would favor certain genes or wipe others out. From here I can't see what that would look like; but I can only see it's possible.

JOHN HOCKENBERRY: Widespread disease: Hmm…well, could that be something like AIDS?

MNEMNOSYNE: Well, that’s possible. There's no evidence AIDS is having any effect on the gene pool now. But it can tell us something about our history. You do know that there are some people who seem to be resistant to the AIDS?

JOHN HOCKENBERRY: Yeah I've heard that.

MNEMNOSYNE: Well, there's a gene researchers call the CCR5 gene. It makes a protein and that protein acts as a sort of doorway say for HIV infection. It allows the infection to come in. But some Europeans have a mutated form of the gene. If you happen to have two copies of this mutation, say one that you inherited from your father, and the other from your mother, then the protein doesn't get made. It's wiped out; there's no doorway for the virus. So having the mutant gene can protect you from getting AIDS. But then the question is, how did these Europeans come to have the mutation in the first place? Here's Dr. Steven O'Brian. He’s the chief of the Laboratory of Genomic Diversity at the National Cancer Institute:

STEVEN O'BRIAN: When we looked at the frequency of the mutation in modern human populations, it was present at a very high frequency. 15 percent in Sweden, and 10 percent in Germany and France, and 5 percent in Italy and in Turkey. Well, that’s a large number. How did it get that high? Well, the simplest explanation that fits all the data led us to the conclusion that maybe it got to a high frequency in history by some sort of strong, breath-taking natural selection pressure, something that caused people who carried it to be favored and live longer. And the simplest explanation that made sense for something like that was a plague or a disease, something that killed thousands of people.

MNEMNOSYNE: Researchers had a hunch that this mutation of the CCR5 gene was not an old one. For one thing, it's never found among native Africans. So, they think it must have developed sometime after humans left Africa when they began migrating through the rest of the world. O'Brian did some fairly simple math on the rate at which the gene mutates and he came up with a date. He says it's not all that hard to figure out. Basically, you compare the original form of the gene with the mutated form and you see how much difference there is between the two. Then you ask yourself how long it would take over time for that much difference to build?

STEVEN O'BRIAN: It's quite a simple equation, in fact you can do the calculation on a five-dollar calculator from K-Mart. It's that simple. But it’s kind of interesting because the genome has been nice enough to give us all these little markers that are really molecular time-keepers; they allow us to track in time events that occur in the genome. When we did the calculation, it came out that the mutation probably arose about 700 years ago, around 1300, which was forty years before the Black Death.

JOHN HOCKENBERRY: Wow...the black plague. So a mutation which may have helped people survive one epidemic turns out to do the same thing hundreds of years later with a different epidemic.

MNEMNOSYNE: Yeah, that’s right but, unfortunately, it doesn't help that many people. We can't see how it will have much effect on the AIDS epidemic, and certainly we can't predict that it will have any over-all effect on human evolution.

JOHN HOCKENBERRY: So there's no real practical advice you could give me for the future, is
there?

MNEMNOSYNE: Oh yeah, sure there is. In the long run, you should move.

JOHN HOCKENBERRY: Move out of New York? I've considered it...what…what do you think, Connecticut? California?

MNEMNOSYNE: Oh no, much further than that.

JOHN HOCKENBERRY: How much further?

MNEMNOSYNE: Well, you hear the clock?

JOHN HOCKENBERRY: Yes.

MNEMNOSYNE: That's the cosmos, that’s evolving in its own way along with you...

JOHN HOCKENBERRY: Ah, you're taking the long view again, aren't you? I know all about that. I know the solar system is unstable. In -what is it, a couple of billion years-the sun is going to use up all the hydrogen it burns for fuel. Then it swells up like a balloon, swallowing the earth and all the DNA on it.

MNEMNOSYNE: And then the sun deflates; it shrinks to a white dwarf, freezing any bit of DNA that hadn't previously already been fried to crisp.

JOHN HOCKENBERRY: Oh, come on, that's a long time off. We humans are smart. We've already been to the moon, OK. We've got our eyes on Mars. Eventually—well, by the time the old neighborhood goes bad I expect my descendants will be out of here; we'll be living out by Alpha Centuri or something.

MNEMNOSYNE: Well, yeah, but as long as they're in this universe, they're stuck with an expanding cosmos…

JOHN HOCKENBERRY: Right.

MNEMNOSYNE: …where the space between things keeps growing. Space just grows and
grows and sooner or later every single molecule, it doesn’t matter where it is, will come apart. Things will disintegrate. Even the atoms can't hold together. In the end…

JOHN HOCKENBERRY: Oh, please…get a life.

MNEMNOSYNE: ...Did I mention the infinite stillness, the infinite silence…

JOHN HOCKENBERRY: The infinite silence…why are you telling me this?

MNEMNOSYNE: …The infinite cold? Well, you wanted perspective. In the long run the drama of human evolution is such a minuscule event-

JOHN HOCKENBERRY: Minuscule event-...Minuscule event? Oh. Wait, that reminds me. Sorry, gotta shut you down now.

MNEMNOSYNE: Why? John, wait.

JOHN HOCKENBERRY. Gotta use the computer for something else.

MNEMNOSYNE: Wait.

JOHN HOCKENBERRY: Something important. Note to self: Pick up baby formula on the way home. Find out if we need diapers. Pick up application forms from Ivy League colleges. Hey, gotta start early. Check with pediatrician. Ask insurance company if homeowner's policy covers eventual cosmic disintegration. Yeah, it must cover it. Sure. What’s the deductible on that? That’s kind of wild.

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Credits for The DNA Files:

The DNA Files is produced by SoundVision Productions in Berkeley, California, and is made possible through the generous contributions of the National Science Foundation, the Department of Energy, and the Alfred P. Sloan Foundation.

JOHN HOCKENBERRY: You’ve been listening to The DNA Files. I’m John Hockenberry.

For more information and for an interactive look at some of the issues behind this program, go to our website at www.dnafiles.org. For tapes and transcripts of this program and this series, contact VisABILITY, at 303-823-8000. That’s 303-823-8000. To contact The DNA Files, send your email to feedback@dnafiles.org. The DNA Files Executive Producer is Bari Scott. The Project Director is Jude Thilman. Today's program, "The Genetics of Human Evolution: Where Did We Come From? Where Did We Go?", was produced by Larry Massett. The program was engineered by Robin Wise and edited by Ann Finkbeiner. The role of Mnemosyne was played by Carolyn Lawrence. Original production music by Larry Massett.

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Managing Editors of The DNA Files are Loretta Williams and Catherine Stifter. Production Manager is Catherine Gollery. Technical Director is Robin Wise. Adi Gevins is Director of Research and Creative Consultant. Sally Lehrman is Content Consultant. Original music composed and performed by Bill Frissell. Introductory feature produced by John Rieger and edited by Gary Covino.

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This has been a SoundVision production.

This program is distributed by NPR – National Public Radio.