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Science Talk

Alcoholism and Genetics; and Why Aren't the Pioneer Spacecraft Where They Should Be?

In this episode, psychiatric geneticist Laura Jean Bierut talks about her article in the April Scientific American about the influence of genes on alcoholism. And Scientific American editor George Musser discusses the March 26th Isaac Asimov Memorial Debate at the American Museum of Natural History that dealt with the discrepency between the calculated and actual positions of the Pioneer spacecraft. Plus we'll test your knowledge about some recent science in the news.

Welcome to Science Talk, the weekly podcast of Scientific American for the seven days starting March 28th. I am Steve Mirsky. This week on the podcast, genetics and alcoholism with psychiatric geneticist Laura Jean Bierut. And a pioneering mystery – we will talk with Scientific American editor George Musser about a session here in New York, Monday evening, at which scientists discussed what they thought was going on with the Pioneer spacecraft, which are now out of the solar system. From launch to last contact, the positions of the ships were not quite with the equations predicted, so what's up? Plus we'll test your knowledge about some recent science in the news.

First up, Laura Jean Bierut. She is associate professor of psychiatry at Washington University in Saint Louis. With John Nurnberger, she coauthored the article "Alcoholism and Our Genes" in the April issue of Scientific American. To find out more, I called Bierut at her office in Saint Louis.

Steve: Hi Dr. Bierut. How are you today?

Bierut: Hi Steve.

Steve: First of all, you are a psychiatric geneticist. What exactly does that mean?

Bierut: I am trained as a psychiatrist, so I have my medical degree and specialized training in psychiatric disorders such as alcoholism, depression, schizophrenia, and I also have training in genetics so to understand how illnesses are transmitted through families, and so we are trying to look at how mental illnesses and addictions are transmitted in families and understand the underlying genetic causes of them.

Steve: Genetic causes or genetic predispositions?

Bierut: Yes! Genetic predispositions in that it could also be a genetic protective factor.

Steve: You talk in the article about this study, this big multi-institutional study that you're a principal or you're a participating investigator in the collaborative study on the genetics of alcoholism. Can you briefly give us an overview of that study?

Bierut: Yes! This is a study that began in 1989 and is funded from the National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health. And This is a large multisite study across the United States and it has been recruiting alcohol-dependent individuals and their family members for over 15 years now. and The goal of this is to characterize these individuals, interview them, understand what type of symptoms they have, and then to move this into the laboratory so that we could begin to understand some of the neurologic predispositions, because in addition to interviewing the subjects, we performed neurophysiologic tests and then we've also collected blood samples for genetic tests so that we could do subsequent genetic testing on this and understand the relationships between their clinical predisposition, their neurophysiologic aspects, and specific genes and gene variants.

Steve: So when you see alcoholism in a cluster in a family group, that's a signal to you that even though there might be an environmental component, perhaps it's at least worth looking for a genetic component?

Bierut: Yes, absolutely. And clearly alcoholism, like many of our common diseases—hypertension, diabetes, cancers—there are both biological predispositions, genetic predispositions, but also environment plays an important role. When we see this family clustering, we begin to think that there is something in these families that is predisposing them and we know from twin studies that most of the family clustering is related to genetic factors in that family.

Steve: That's really interesting, the actual methodology you talk about in the Scientific American article. You're doing EEGs on some of these people and by looking at the brain waves and then looking at the genetic profiles, you actually learn quite a lot. Can you just talk about that a little bit?

Bierut: One of the things that was identified in the 1980s was that several laboratories began demonstrating that certain times, types of electrical activity in the brain could mark the difference between an alcohol-dependent individual and a person who didn't have alcohol. When you look at those types of studies, they're always confounded because you'll always say, "Well are these brain activities differences related to alcoholism that the person has or is it related some underlying biologic activity of the brain?" These studies were extended then to the children of alcoholics and children of non-alcoholics, so looking at adolescents and young adults before they initiated their drinking or before they went onto any type of heavy drinking. And what was very interesting was that it was revealed that you could identify that the children of alcoholics had different patterns of brain wave activity than the children of the non-alcoholics, so it really seems to be a biologic predisposition.

Steve: And those brain wave patterns that were different were related to their genetic makeup?

Bierut: Yes! So subsequently people have been looking at this type of brain activity and this brain activity is very highly related to a person's genetic makeup, and they've looked at this through twin studies again, showing that identical twins had more similar patterns than non-identical twins. So this is an underlying biologic predisposition – it's called an endophenotype, where it's the idea that it's a marker for an illness that could be measured and is more closely related to the genes that are involved. So part of this collaborative study of the genetics of alcoholism was that we wanted to include not only the clinical interviews of someone's alcohol use—alcohol problems, alcohol dependence—we wanted to incorporate some of these biological measurements to guide our genetic studies.

Steve: So you might have a gene for a particular brain receptor or, I think what you talk about in the article is not actually the structure of the receptor molecule, but the amount of receptors that you actually produce?

Bierut: The brain is a very complex organ and what's clear is these different types of brain wave patterns are related to numerous complex in our actions between neurotransmitters and some of the brain receptors, and it's some of the balance between how much of these proteins are produced—how are they regulated—are likely to be involved in some of these biologic predispositions. Most of our findings so far have not been in [the] actual structure of the proteins, but appear to be in more of the areas that are likely related to the regulation of how much of the protein is produced. And GABA neurotransmitter is one of the most common neurotransmitters in the brain and it is an inhibitory neurotransmitter that it’s [is] kind of dampening the brain wave activity. And so we found a variant in one of the GABA receptors [that] is associated with alcoholism, and this fits in with some of the brain wave pattern activity that it looks like alcoholism [and] is linked to disinhibition, so [it's] a problem with the inhibition of brain waves that people should generally have.

Steve: And that manifests in that you have excessive risk-taking behavior or, specifically related to the drinking behavior, you might need to drink more before you get the same effect than somebody who doesn't have that genetic profile.

Bierut: The way that we generally think about it is that this disinhibition is in with behavioral–undercontrol, impulsivity, risk-taking, kind of making some poor choices at times, so drinking those extra drinks when you maybe shouldn't or drinking at a time that you shouldn't, and some of this loss of control that you may have over certain behaviors.

Steve: This is really interesting material, I think, because perhaps many of the listeners are familiar with older research, for example, that found that the aldehyde dehydrogenase enzyme is not available for certain people, and that for them, drinking in excess is really uncomfortable, so they tend not to, but that's more of a direct genetic biochemical kind of a system related to the alcohol molecule ultimately as it gets metabolized. But here we are talking about actual behaviors related to the molecules in the brain based on the genetics.

Bierut: So there are multiple different pathways to alcoholism and some of them are pharmacologic-type pathways of how a person metabolizes alcohol – how they respond to it with the alcohol dehydrogenase or acetaldehyde dehydrogenase, two important enzymes that are involved in the metabolism of alcohol, and we would kind of think [of] that as a more direct alcohol-related route to the development of alcoholism. And as you said, there are these variants where people have difficulty breaking down the alcohol metabolism, and so drinking to excess is uncomfortable, and this is common in the Asian population as where it's most frequently seen. But then we have these other variants that are the GABA receptor, which is much more of kind of a general disinhibition, so it's a general type of predisposition that a person has, and individuals are at risk for a variety of different behaviors including alcoholism [and] other types of impulsive behavior.

Steve: What do we do with the knowledge that you generate?

Bierut: With this knowledge, I think, we are starting to understand some of the basic biologic pathways that are leading to alcoholism. Alcoholism is a complex behavior. There are multiple different routes to becoming [an] alcoholic and by understanding these different pathways, it opens up different types of treatment options and also gives us further knowledge about what are the risks. So one of the aspects that we could think about are pharmacologic treatments – can we begin to target these different pathways and these different predispositions that a person has, so treatment for their alcoholism is most effective? At this point, our treatment for alcoholism is very general. We have a handful of medications that we use and we do not differentiate the clinical picture at all, which, you know, kind of pick one of these medications and use it. But understanding an individual's biologic predispositions they hopefully help[s] us personalize the treatment to that specific individual so that we could target medications and hopefully improve the effectiveness.

Steve: So that if the underlying biological situation seems to be a dearth of GABA receptors, perhaps a therapy that increases, that amps up the levels of the GABA receptors might be efficacious?

Bierut: Right! . And there are different medications that we could think about now that influence, you know, the GABA system and some of our treatments—some of the newer medications like topiramate—influences this system and we could think that, ah, if you have this biologic predisposition in the GABA system, you may respond better to this type of pharmacologic treatment.

Steve: Very interesting. The article is "Alcoholism and Our Genes" in the April issue of Scientific American. Dr. Bierut, Thank you very much.

Bierut: You are very welcome.

Steve: The entire article by John Nurnberger and Laura Jean Bierut is available free at our Web site, www.sciam.com.

Now it's time to play TOTALL.......Y BOGUS. Here are four science stories. Only three are true. See if you know which story is TOTALL.......Y BOGUS.

Story number 1: Ladybugs are becoming a nuisance to the wine industry by being harvested in large numbers along with the grapes.

Story number 2: New sunglasses will allow you to personally tune the lenses to make them lighter or darker.

Story number 3: Migratory birds appear to be the major cause of new cases in new regions of avian flu.

And story number 4: Researchers have found a pair of semi-identical twins that came about when two sperm fertilized a single egg, which then split in two to give rise to two individuals.

We'll be back with the answer, but first, the Pioneer 10 and 11 spacecraft were launched in 1972 and '73 and have since left the solar system. They both carried a plaque, you may recall, with an image of a man and a woman, the hyperfine transition of neutral hydrogen, the position of the earth and solar system, and some other info of possible interest of the lawyers for any intelligent beings whose house the things may slam into some distant day. Oddly, right up to the last contact with the ships, scientists found that the positions of [the] spacecraft didn't quite match predictions. So what's going on? Something still unknown in physics or just a glitch in the ship designs? Well, on Monday night at the American Museum of Natural History here in New York, a panel of engineers and physicists threw out ideas about what's been called the Pioneer anomaly. Our own space expert George Musser was in the house and on Tuesday I asked him to brief us about the discussion.

Steve: Hi George, how are you doing?

George: Good Steve, how are you?

Steve: Good. Tell me about what is the Pioneer anomaly, first of all.

George: Well, it's a strange thing happening with two of NASA's space probes, the Pioneer 10 and 11 space probes. Back in the late '70s they flew by Jupiter and Saturn. They were the first human missions to those two giant planets and then afterwards, they just shot out of the solar system and are now heading into deep interstellar space. and They've been tracking those spacecrafts up until the radios on them failed some years ago and found that they weren't where they should be – their positions were [a] little bit off from the calculated positions. So they went back to the calculations and put in the effects of the gravity of the planets. They put in the effects of Einstein's theory of relativity. They even put in the effects of the galaxy, you know, dark matter, and they still couldn't explain the positions of those spacecraft.

Steve: So there was this symposium on Monday night at the American Museum of Natural History, and you were in attendance, where a panel of experts threw out various explanations for the anomaly.

George: It was an interesting panel because if you hadn't really known anything about the anomaly beforehand, you wonder, what was the big deal about it? Then the panels were basically saying, probably the anomaly can be explained with some kind of ordinary effect ndash; a gas leak out of one of the tanks. And one of the interesting results that was discussed that I had not heard about before was the possibility of heat escaping from the probes in an asymmetric pattern. So this actually had been broached some years ago—that if heat is escaping from the surfaces of the spacecraft in a particular direction, it might explain the anomaly. You could. A little kick as the photons of light came off the spacecraft—they would give a little kick to it as they came off.

Steve: A little rebound…

George: A little rebound, in fact. Exactly.

Steve: And the heat is coming from…

George: So the heat is coming from the electronics onboard the spacecraft, which are [is] ultimately powered by a plutonium power source.

Steve: So the plutonium, it's a radioactive power source.

George: Exactly!

Steve: So there is some heat directly from the power source as well as the electronics.

George: Right! And what makes it a complicated problem, and why it's only been recently that the engineers have been able to reconstruct what happened on the spacecraft, is that [a] lot of surfaces that are pointing [at] funny angles – the plutonium generators are actually out on booms, extended away from the spacecraft. So it was postulated, I don't know, maybe 10 years ago or so, that heat might explain this anomaly. They've been working on this problem for a long time as you can tell. But [it] is only now really, in fact, one of the engineers (unclear) last night described some of the particular calculations he had gone through to try to explain the anomaly, and he thinks he can get approximately of about half of it explained through heat.

Steve: Is it an important problem or is it just an interesting problem?

George: Yeah. This is something that people debate a lot and let me just step back for a second and look into this. The theories we have of nature right now are extremely precise, extremely accurate, so we are talking Einstein's theories, Newton's theories, quantum theories and so forth. So necessarily, any effect that's breaking those laws, any new effect of physics that might indicate string theory, for example, or a new law of gravitation, will necessarily be very, very, very small. So you're looking at effects that potentially, if they even exist, and this Pioneer anomaly is an example of one that are [is] down in the noise. So if they were to find that this Pioneer anomaly is real in the sense that it cannot be explained by gas leaks or cannot be explained by heat or gravity of some other object out in the solar system, it might indicate a new law of physics.

Steve: But that's the last place you're going to go. You have to really exhaust every possible conventional explanation before you start throwing around new laws of physics, right?

George: Oh, yeah! Of course. What's funny about this kind of discussion on the Pioneer anomaly is that everyone is interested in it because of the potential for a new law of physics. If we're just showing there is a gas leak in some distant spacecraft, you know, who really care[s]? So they don't think it's a new law of physics, but they really need to chase down every possibility.

Steve: And all the conventional explanations like the ones you mentioned, some gas venting—and it could be a tiny, tiny amount of gas venting or this kind of heat radiating off the spacecraft—all the conventional explanations still don't get you the entire error in the position of the spacecraft.

George: That's right! I should say it's not really known whether they do, because people can say what's probably heat coming off, it is a plausible explanation, but they have to actually go through the calculations to know whether that can handle the anomaly. The anomaly is about a 10 billionth of the acceleration due to gravity on earth, so it's a 10-billionth g of a g force, so it's a very, very small effect you're looking for and the kick you get, the rebound you get from light and heat coming off the spacecraft, is also very, very small. So you're talking about a lot of tiny little effects that they have to track down. They check them off their list, go to the next effect, check it off, go to the next effect and see whether it can explain the anomaly.

Steve: So you're fairly well versed in this, I mean, as a reporter you've been following it for years.

George: Yeah!

Steve: So what do you think?

George: Well, you know, it's one of these "hearts versus heads" kind of things. My head tells me it is probably a gas leak or heat leak, but my in my heart I really want to believe that this is some new law of physics that they are finding. And it's as I said earlier, any new effect of physics will be necessarily very, very tiny, because the laws of physics we have are so successful so far, although they are probably incomplete.

Steve: Like we are finding new microbial species, we're not finding any new elephant species.

George: Something like that. Exactly. So if you have, you know, a 100 anomalous effects, different particle effects, different astronomical effects, and this case of spacecraft effect, you have to go down each and every one of those 100 to find the one or the two that really are new physics, so this is one of those 100 odd effects that are being considered. It may not be the capital E effect, but they have to look into it.

Steve: And since we and nature have apparently combined to throw this interesting set of data at us, we might as well look at it.

George: Yeah! That's what looks so exciting about the effect. Even [if] it turns out to be not new physics, just from an engineering point of view, it's incredible. They are tracking, you know, 90 times further than the earth is from the sun, the spacecraft, with an incredible precision into the kilometers. To look for effects that can be due to things that on earth would mean nothing—the rebound due to the light, tiny little gas leaks potentially, gravity of other planets—it's very, very small. So it is just from the engineering point of view, this has just been a tour of reports. They have gone back to the tapes, the manuals that were written in the '60s and '70s about the spacecraft. They dug out old many of those computers to transfer all of the old data on to modern machines, so it's been a kind of fine detective search. That's why I've been following it for, goes on 10 years.

Steve: Interesting stuff. Thanks a lot George.

George: Thank you Steve.

Steve: For more on the Pioneer anomaly, just Google the phrase "Pioneer anomaly," which probably you would have done anyway, you slyboots, and also check out George Musser's article—it's not about the Pioneer anomaly—it's in the new section of the April issue of Scientific American. It's about the possibility that dark matter may in fact emit some detectable energy, and is therefore called the not-so-dark matter.

Now it's time to see which story was TOTALL.......Y BOGUS. Let's review the four stories.

Story number 1: Ladybugs in the grape harvest hurting wines.

Story number 2: Sunglasses with tuneably tinted lenses.

Story number 3: Migratory birds to blame for spreading avian flu.

And story number 4: Semi-identical twins found.

Time is up.

Story number 1 is true. Ladybugs in the wine are making some wines a little funky. The bugs get harvested with the grapes, but produce some chemical compounds that can make wine makers whine. These compounds can smell like peanuts or green peppers. Now watch your wine, your Cabernet. For more, check out the Tuesday March 27th edition of the daily SciAm podcast 60-Second Science.

Story number 2 is true. Chemists at the University of Washington are developing sunglass lenses that allow you to turn a little dial and change the intensity of the tinting. They announced that last week at a meeting of the American Chemical Society in Chicago. The lenses feature what is called an electrochromic polymer that changes hue in the presence of an electric current and that's provided by a tiny battery.

And story number 4 is true. Researchers have found a pair of twins who are identical on the mom's side but who share half the genes on the father's side. Two sperm cells from the same father apparently fused with the egg, which then split in the same way that typical identical twins come about. Three rare events came into play here for this discovery. [First,] a doubly fertilized egg became a viable embryo. This sometimes happens, giving rise to so-called chimera – a single individual with two distinct genomes. Second, you have to have the early split to get the twin embryos. And third, somebody has to recognize that the kids are in fact chimeric twins. In terms of genes in common, the kids are halfway between fraternal and identical twins. The report appeared in the Journal of Human Genetics.

All of which means that story number 3 about migratory birds being the major cause of the spread of avian flu is TOTALL.......Y BOGUS. Because a study just out in the ornithological journal Ibis concludes that human commercial activities, particularly those associated with poultry, are the major factors in the global dispersal of avian flu. A close examination of the flu's pattern of spreading found that it did not in fact coincide with the main wild bird migration routes. According to the report, "mass movements of commercial poultry without strict health control is a more parsimonious explanation for avian flu spread."

Well, that's it for this edition of the weekly Scientific American podcast. You can write to us at podcast@sciam.com. Check out news articles at our Web site, www.sciam.com. The daily SciAm podcast 60-Second Science is at the Web site and at iTunes, and welcome back baseball. We have a baseball show for you next week. For Science Talk, the weekly podcast of Scientific American, I am Steve Mirsky. Thanks for clicking on us.

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