Viruses against Disease; Going Batty for Bats

Scientific American editor in chief, John Rennie, talks about the contents of the December issue, including bat evolution and how magicians are helping neuroscience. And Boro Dropulic of Lentigen talks about converting viruses into disease fighters. Plus, we'll test your knowledge about some recent science in the news. Web sites related to this episode include http://www.sciam.com/report.cfm?id=bat-guide; http://www.sciam.com/report.cfm?id=thanksgiving

Podcast Transcription

Steve: Welcome to Science Talk, the weekly podcast of Scientific American for the seven days starting November 26, 2008, I'm Steve Mirsky. This week Scientific American editor in chief, John Rennie, talks about some of the highlights of the December issue and researcher Boro Dropulic talks about using viruses to fight disease. Plus we will test your knowledge about some recent science in the news. First up John Rennie; we talked in the library at Scientific American.

Steve: December's issue is out and people have to look at the bat evolution article.


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Rennie: That is a beauty.

Steve: Even if they don't read it, just look at the pictures—what amazing photographs!

Rennie: They really are. The photographer did a wonderful job of capturing what's so beautiful and fascinating about bats, and the rest of the article really looks at the evolutionary question of what makes bats the fascinating animals that they are. Bats are a way more successful group of mammals than most people would ever realize.

Steve: What does the article say, 20 percent of all mammalian species are bats?

Rennie: I believe they are the most successful mammalian group for that reason, and I mean, it's astonishing and they are found basically everywhere. The two major evolutionary adaptations that make bats what they are and of course go to making themselves successful seem to be obviously flight, because they are the truly flying mammals and echolocation, really distinctive. And one question that has puzzled biologists for a really long time was which came first in that sense. Were these flying mammals that learned learnt to echolocate or were these animals that were using sound to locate things in the dark and flight started to come along? After that, starting to look like they were getting some answers that flight came first, but it's a fascinating question and there are lot of mysteries about how bats arose.

Steve: The bat anatomy, just the images of the bat skeleton, I may not have seen bats in my whole life. I live near the Bronx zoo, you've [got] flying foxes there that are just flying around free, but I never appreciated [that] the bones that are analogous to our hand and finger bones are immense compared to the body size.

Rennie: Right. Well, because that's one, I mean, basically when a bat flies it's doing the equivalent of waving its hands in the air.

Steve: Right, just the hands.

Rennie: Yes.

Steve: Not really the … well that's the arm bones as well, but that you got to see, you just have to see it—I mean this is, I am violating radio rules here—you got to see this, because it's as if your index finger was the length of your entire body.

Rennie: Yeah, I mean it's astonishing, the kind of adaptations you see in bats.

Steve: And, man, … some of the close-ups of their little creepy faces.

Rennie: (laughs)

Steve: So, we also have a terrific article on magic.

Rennie: Yes.

Steve: And it's not just kind of superficially popped into the magazine. It actually bridges some interesting issues in neuroscience.

Rennie: Right, there was actually a scientific paper that appeared not too long ago in the journal Nature, and also some presentations at some scientific meetings, talking about the subject of the relation between magic and the brain. We are not talking about Harry Potter or the hocus-pocus kind of magic.

Steve: But we are talking about real magic.

Rennie: Conjuring, man. That's right. A slight of hand and all the rest. Obviously, as magicians have always said that the key to magic is very commonly misdirection. It's basically a matter of creating certain kinds of illusions in the minds eye of the audience and they accomplish this by often, in effect, getting people to pay attention to one thing when something really important is going on someplace else. In effect, they are getting our brains to fool us and enlisting sort of, you know, our own inattention. But this has become interesting because what it means is in a lot of ways the magicians have been intuitively using for a very very long time certain kinds of truths about how it is that our brains pay attention to things that neuroscientists are only just starting to figure out now. And conversely, [a] lot of the neuroscientists are starting to look at how magicians pull off certain tricks as a way of trying to figure out more about what's actually going on inside our brains that we fall for this kind of misdirection.

Steve: And there is something that magicians do that actually take advantage of the way our brains process information, so that it is not a question of, you didn't pay attention to something—you are not capable of seeing certain things that they do.

Rennie: That's right. I mean, in effect, it's the sort of thing of finding out that, in effect, you can only pay attention to one thing at once. So, even if when you are monitoring or seeing, if you think you're watching, you know, what the magician's left hand is doing as it's moving the little cups and balls around, if the magician suddenly does something that genuinely draws your attention with the other hand then that's the moment when the magician can manage to do something, you won't see at that. Even though you think, you're paying attention. This is what one of the things that they discovered, is that in many cases, it's the point of the attention of what you're paying attention to, not necessarily your gaze that's shifting.

Steve: Yeah.

Rennie: Even if you constantly fix your eyes on one thing, you may still actually be paying attention to something

thing, kind of, out of the corner of your eye.

Steve: Yeah, it's really amazing. I mean, you would think that every man out there would be very aware of a woman's dress being ripped off on stage, and yet you're incapable of actually appreciating it as it's happening.

Rennie: And that can be the key to certain kinds of tricks that the magicians will then play. I mean, they point out that there are a number of experiments, for example, that have demonstrated how astonishingly bad we are at paying attention to things that go on in scenes. There's a famous one that involves getting people to try to count a basketball being passed among a bunch of players.

Steve: I have done that one.

Rennie: I think we all have, and you can't believe it, but the fact is that that this goes on and they get somebody to walk through the scene in a gorilla suit.

Steve: Right across the court as these guys are passing the ball to each other.

Rennie: Squarely through the middle of the field—and most people are never ever aware of this.

Steve: I didn't see it.

Rennie: Because they are fixating on a particular challenge, counting how many times the ball is being passed and they literally don't even see it. They are not even aware that something interesting happened that way. So this is the kind of thing that magicians have been doing for a long time, and this is a fun article because it was written by a couple of neuroscientists but they had a lot of assistance from very well known magicians like the Amazing Randi and Penn & Teller. So it's a fun article. People should definitely take that one in.

Steve: Pen & Teller grace our cover in fact.

Rennie: Indeed they do.

Steve: A little portion of the cover.

Rennie: Yes.

Steve: Most of the cover talks about this very fascinating moon of Saturn.

Rennie: That's right. That would be Enceladus which is, you know, it's a tiny little ice ball of a moon. You wouldn't expect very much of it to be interesting but it turns out to be one of the most fascinating moons in the outer solar system. Because even though it's very, very cold it turns out that it's geologically seismically active. The Cassini probe inspecting it has noticed that there are these geysers of steam and ice that are shooting out apart of the south pole. Now this is very, very strange because normally you need something big the size of a planet for there to be enough internal heat for there to be something like geysers. And, as this article is explaining, it appears that that some of the heat that Enceladus is manifesting is generated by tidal forces pulling on it; that Enceladus may actually be an ice covered body that has a significant liquid ocean just under that ice and that there may be a lot of liquid, that liquid may be sloshing around in a way and that may be, sort of, part of what's creating this sort of friction that generates that internal heat in response to tidal forces. It may also still be warm from some kind of impact that happened who knows how long ago and some of that is still

leaching[leaking] out. But it is all really interesting because there seems to be this internal heat and there seems to be water and these geysers of water crystals and so forth coming out of the south pole thattheyseem to contain a lot of organic compounds. Enceladus has basically joined that short list of places like Mars and Titan in our solar system that are now major points for looking for extraterrestrial life.

Steve: It's as if Saturn has reached out a creepy little hand and it is squishing it, like a little squishy ball until it heats up.

Rennie: Right, that's one way of sort of thinking what the tidal forces are actually doing to it.

Steve: So that's on the cover. There is another really interesting article about developing; we call it "Driving Toward Crashless Cars". If not crashless at least ways to really lower the frequency of crashes, and it's interesting that there is some connection to the magic article. Because they're trying to incorporate technology that fools you into being a safer driver.

Rennie: (laughs) Yes that's right. I mean the problem is a lot of accidents are caused by the fact that we don't pay attention when we drive; and so one of the key is—to sometimes improving our safety as drivers might actually be

to—for the cars to be communicating things to us to make sure we are paying attention to the right things. This becomes increasingly important because quite frankly the population is getting older and older all the time. The older drivers, I mean, unfortunately, [it] is a point of fact that they often are not paying as close attention as younger drivers are. So you want to definitely make sure that they can be kept safe.

Steve: There are more and more gadgets that people are playing with in the car while they should be driving.

Rennie: That's right and …

Steve: Don't stop listening to this podcast until you come to a red light.

Rennie: (laughs) So automakers are increasingly working on trying to build in some kinds of systems that will make our cars safer and that in some cases, as you say, they'll help us, alert us the drivers to things we should be paying attention to. For example, [if]

arewe [are] drifting out of a lane of traffic, something that corrects it, makes us aware of it, so we can get back into the right lane. But in some other cases giving a kind of intelligence to the cars to make sure that when something is going wrong, if a collision is imminent and maybe we are not responding to it as well as we could be, that the car can actually intervene. You know, the things like antilock brakes are sort of the first generation version of this that everybody is familiar with, so that if I stomped down fast on the brakes of my car to make sure I don't go off into a skid. Well there are more and more sophisticated forms of this that are coming along. All of this starts to point us toward a day when, you know, cars may increasingly be not just automobiles but autonomous, and they may be those who do most of the driving themselves. But obviously that can't happen until such time as the cars are able to watch out for our safety.

Steve: Coincidentally, my car is in the shop right now getting a new antilock-brake sensor installed.

Rennie: You may want to have some of those other big upgrades in the process.

Steve: If it's possible. I'll check with the folks at Budget Muffler.

Rennie: (laughs)

Steve: We have got this article on Peptide nucleic acid. We have got an article that gives you some tips on how to avoid being a phishing victim—p-h-i-s-h—online and the other usual collection of columns and short features, news articles and brain teasers and fun letters from our readers that you can find in every issue of the Scientific American.

Rennie: Every single issue.

Steve: Is it amazing.

Rennie: The December issue of Scientific American, on sale now.

(music)

Steve: The December issue, including the bat article with all those spectacular images, is available on our Web site. We also have a three-part video featuring the article's author Nancy Simmons of the American Museum of Natural History. Look for the field guide to bats in the biology section of SciAm.com. Researcher Boro Dropulic recently stopped by our offices. He is the founder and chief scientific officer of a company called Lentigen. We spoke in the SciAm library. They are using an interesting idea to try to attack disease.

Dropulic: We are using a virus, and what we are doing is we're gutting that virus and putting in medicines to help treat a series of diseases. These things are called vectors, the things that deliver genes into cells, and I kind of like to think of vectors is like trucks. We have a truck that will deliver something into a cell, and then you have a payload; and in this case the payload is a gene that can be therapeutic for particular diseases.

Steve: People are probably used to hearing about viruses as vaccines, but perhaps not as the actual treatment; and evolution has really done a lot of this work for us because over certainly hundreds of millions, probably billions of years, viruses have achieved this ability to very efficiently get inside your cells and insert their genetic material.

Dropulic: Yes, different viruses work for different types of animals. There are plant viruses, there are also human viruses, and we are using a human virus to very efficiently deliver therapeutic genes into human cells.

Steve: And talk about some of the specifics. What are some of the various ideas about what conditions can be attacked in this way with the viral vector?

Dropulic: All sorts of serious diseases, for example, cancers, infectious diseases like AIDS, autoimmune diseases, genetic diseases—all diseases for which there are no good present solutions.

Steve: I know one of the things that you're working on first is a way to increase the amount of time you have when dealing with the flu virus; to really figure out, what the construction of your vectors payload should be. Why don't you talk about what the problem with the current vaccine system is and how this kind of a system might give you some more time to make it more specific when you attack the thing?

Dropulic: Yes, so we have a delivery system that can very efficiently deliver genes into cells, and in this case it is the influenza genes, and we can make a vaccine using this system very rapidly compared to conventional methods because of the efficiency of the delivery. So in contrast to making the vaccines over months, we can condense it to a much shorter timeframe. So that we can actually stop production, or we hope we will stop production, of that vaccine later in the year to get an exact strain match for each influenza virus.

Steve: Because currently, it's an educated guess as to what the genetic make up of the next year's flu is going to be.

Dropulic: Because manufacturers have to stop production so early. They have to make an "educated guess" of what that strain will be rather than it being the exact strain. So in many cases the strain is wrong, and so by having a rapid manufacturing platform, we can delay the time in which we start so that we can ensure

to[that we] have a genetic match before we start manufacturing.

Steve: Another of the conditions you're working on is graft-versus-host disease when somebody has a transplant. If things go wrong, the body's immune system attacks the transplanted tissue and it's devastating. And so how would this kind of viral vector system work in that situation?

Dropulic: Right. So, allogenic transplantation is a known way to cure many leukemias, many forms of cancer. Unfortunately, there comes a price that those cells from the donor that are transplanted into the recipient—that's what's called an allotransplant; it can sometimes attack the host, leading to what is called graft-versus-host disease. We have a genetic switch; what we do is as we place this genetic switch into the vector and the vector very efficiently delivers that genetic switch into the cells that you then transplant into the individual. If the individual should get graft-versus-host disease, we can turn on that switch and then turn off the graft-versus-host disease effect.

Steve: Right, so this switch comes along for the ride and if you don't need it, you don't have to activate it.

Dropulic: That's right.

Steve: Let's also talk about stem cell protection—and this is not stem cell therapy; we are talking about protecting your own stem cells. And this situation comes up in a certain kind of cancer that you are working on.

Dropulic: Right, so this is to address the brain cancer called glioblastoma, and glioblastoma can normally be successfully treated with a drug called temozolomide, but temozolomide also destroys your stem cells, which are the cells that produce your blood. These are blood stem cells, and so what we are doing is we are using the lentiviral vector to insert a protective gene called MGMT into the stem cells, so that when patients then receive the drug temozolomide, the stem cells don't die but they survive because they now have that protective gene.

Steve: Right, so in this case it's a therapy to protect the body from the other therapy.

Dropulic: Yeah, it's like protecting the cells from a side effect of an existing drug that is know[n] to be effective.

Steve: All right, let's turn over all the cards and reveal to the listeners the secret here that I

don't[didn't] want you to say at upfront because in a court of law it might be considered prejudicial, so we are going to instruct the jury to disregard until now. But this is the really interesting thing, I think to a lot of people. The lentivirus is a family of viruses. The particular virus in question here that you are using as your vector to transport all these genes that are hopefully going to do good things, tell us what that is.

Dropulic: Well, it's derived from the HIV virus, and what we have done is we have muted the HIV virus by taking out all the disease elements and putting in a therapeutic payload and the reason why we use it is, is that this virus,

as faras you said, for millionsfor[of] years has evolved to get into human cells so efficiently. That's why it's such an insidious disease; but then when you take that virus and then mute it, break it up into pieces and then insert a therapeutic payload, it becomes the most efficient [known] way of stably delivering genes into human cellsknown.

Steve: Really interesting idea; you might even be able to use this altered HIV against HIV.

Dropulic: Absolutely. We are going to be initiating some programs where we will use an anti-HIV payload in a HIV vector to inhibit replication of the virus.

(music)

Steve: Speaking of HIV, December 1st is World AIDS Day, devoted to recognizing the ongoing necessity of addressing AIDS and HIV. Check out the in-depth report on HIV and AIDS, the week of December 1st at 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: There is 10 times as much bacterial diversity in the human bowel than had been previously thought.

Story number 2: Chemists have created a sugar molecule with a much higher melting point than sucrose which could give cooks new recipe options.

Story number 3: Exercise can lower a woman's risk of cancer but only when combined with a good night['s] sleep

And story number 4: Speaking of exercise, a study finds that people who keep gratitude journals, simply writing down what they are thankful for, wound up exercising significantly more than a grouchy group.

Time is up.

Story number 4 is true. People who just kept a gratitude journal for ten weeks, writing down things as simple as, I am grateful I woke up today" wound up working out 90 minutes more per week than another group who were assigned to write down things that were ticking them off. Be thankful, you can hear more about this study on the November 24th episode of our psychology and neuroscience podcast 60-Second Psych.

Story number 3 is true.

A n[New] research finds that a woman's risk of cancer drops if she exercises and can get a good night's sleep. Lack of sleep appears to undermine the anticancer benefits of exercise. That's the finding of work done at the National Cancer Institute and presented at the recent International Conference on Frontiers in Cancer Prevention Research. The exact mechanism isn't clear, but it is believed that exercise alters hormone levels and immune function that in turn change cancer risk and sleep modulates the effects of the physical activity.

And story number 1 is true. There is 10 times as much bacterial diversity in our bowels than we thought. That's the finding of David Relman at Stanford, reported in a recent issue of the journal Public Library of Science Biology. He found over 5,600 strains or species of bacteria by looking at variations in DNA sequences. I had a nice interview with Relman about this work on the most recent episode of Science Friday which is available as a podcast, and you can hear an interview we did with Relman about previous work concerning us and our microbes on the May 2nd, 2007 episode of Science Talk; archive down our podcast page SciAm.com/podcast.

All of which means that story number 2, about a sugar molecule with a high melting point is TOTALL……. Y BOGUS, but what is true is that astronomers have found sugar in space. Well, they found inorganic sugar molecule in a particular region of the galaxy where habitable planets might exist. The discovery was published November 25th on the Web site, astropH. The researchers found the molecule glycolaldehyde in a region about 26,000 light-years from us. Glycolaldehyde has been spotted in space before but only in the galactic center where conditions for good planets are bad. The simple sugar could be really important because it can react with propanol to form ribose which is a key ingredient in RNA, which is probably what you need to cook up life.

(music)

Well that's it for this edition of Scientific American's Science Talk. Visit www.SciAm.com for all the latest science news, and check out our in-depth report on the science of Thanksgiving. For Science Talk, I'm Steve Mirsky. Thanks for clicking on us.

Science Talk is a weekly podcast, subscribe here:

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Scientific American editor in chief, John Rennie, talks about the contents of the December issue, including bat evolution and how magicians are helping neuroscience. And Boro Dropulic of Lentigen talks about converting viruses into disease fighters. Plus, we'll test your knoweldge about some recent science in the news. Web sites related to this episode include https://www.scientificamerican.com/report.cfm?id=bat-guide; https://www.scientificamerican.com/report.cfm?id=thanksgiving

Steve Mirsky was the winner of a Twist contest in 1962, for which he received three crayons and three pieces of construction paper. It remains his most prestigious award.

More by Steve Mirsky

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