科学美国人60秒 SSS Attacking antibiotic resistance; William Shockley biography; flu data policy.

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Welcome to Science Talk, the podcast of Scientific American magazine for the seven days starting March 29th. I am Steve Mirsky. This week on the podcast, Scientific American staff writer Gary Stix talks about research aimed at fighting one of the big problems in medicine– antibiotic¹ resistance. Pulitzer Prize-winning journalist Joel Shurkin discusses his new book about controversial physics Nobel laureate William Shockley, and geneticist Steven Salzberg tells us about why he thinks we need a lot more openness in flu research. Plus, we will quiz you about some recent science in the news. First up, Gary Stix. He is the special projects editor at Scientific American magazine and often writes about technology and biotechnology. He has an article in the April issue of the magazine about the efforts of one lab to fight antibiotic resistance in a new and novel way. To find out more, I called Gary at his home in New York City.

Steve: Hi, Gary, how are you?

Stix: Good, Steve, how are you?

Steve: Okay, give me the nickel tour of the work that you talk about in the article. Whose lab is it and what are they doing that's so interesting?

Stix: The researcher who heads this lab, his name is Floyd Romesberg. He is actually a chemist, not a biologist. He has been interested since his postdoctoral days in the early 1990s in the processes that drive evolution. The project that I wrote about was really on basic research that he is doing on understanding the process by which antibiotic resistance develops and finding a way to block the emergence² of resistance.

Steve: Usually, what we try to do now about antibiotic resistance is develop new antibiotics³ that the bugs⁴ haven't had a chance to become resistant⁵ to, right?

Stix: Right!

Steve: And he is trying to get around that.

Stix: This is different. He has found a way to block antibiotic resistance by blocking the mutations that are one way that antibiotic resistance forms, the mutations in the bacteria that allow it to get around the action of the drug.

Steve: So, instead of coming up with new antibiotics, this is a way to make sure the existing antibiotics continue to work.

Stix: Yes! One form of antibiotic resistance operates by blocking a process of very rapid mutation⁶, hyper mutation that the bacterium⁷ goes through to get around the action of the drug. The drug that Romesberg was looking at in this case was Cipro, the drug that was made famous during the anthrax scare, and Cipro has to bind⁸ to a particular protein that causes damage to the DNA⁹ and ultimately results in death of the cell. But by this process of mutation that is actually set off by the initial binding¹⁰ of the drug, the bacterium can get around now.

Steve: The bacterium's progeny¹¹ get around it, right?

Stix: The bacterium's progeny get around it. The idea that Romesberg came up with was to block one of the molecular¹² processes that the bacterium goes through to prevent the drug from binding to it and causing this havoc¹³ of damage to its DNA and one of the ways that that resistance develops. What would ultimately come out of this is not something that would substitute for antibiotic, what would come out of this is another drug that would be administered along with Cipro or perhaps another antibiotic, and that other drug would prevent resistance while the antibiotic did its thing.

Steve: Can you tell me how long do you think it's going to be before, if ever, this thing actually pans out as a useful medicine for human beings?

Stix: Well! Romesberg has already started a company that is in the very early phases of developing a drug. What he actually showed in his laboratory is that…

Steve: Where is his laboratory, by the way?

Stix: His laboratory is at the Scripps Research Institute in La Jolla very near San Diego and what he showed is that this process could be blocked in mice, but they actually have to come up with a small molecule¹⁴ that is non-toxic. It does interact with other essential biological pathways and that also blocks this process and he set up a small company that's actually found some leads that may be promising¹⁵, but the process of drug development is long, arduous¹⁶, and often has a number of pitfalls¹⁷ along the way. So, it’s really hard to predict.

Steve: You've been following developments in this field for many years now. I mean, you are a veteran journalist. So, you obviously thought there was enough here to make it worthwhile to write about for Scientific American.

Stix: Well! The reason I chose this as a topic was because I write this monthly feature that tracks how a technology starts its life from basic science, how it's transferred from basic science findings into the early phases of the technology, and this is a classic example because it goes from an understanding about how evolution works all the way to the early phases of developing a drug. That's it. I wouldn't make predictions about exactly what's going to happen to it. Well! What intrigued¹⁸ me about this is that this was a very interesting way and very unusual way of attacking the problem of antibiotic resistance. Even if this doesn't work, it probably will spur other ideas, either in Romesberg's lab at his company or among other researchers of how to attack the problem.

Steve: Thanks a lot, Gary. I appreciate your time.

Stix: Oh! Thank you.

Steve: Gary Stix's article is called, "An Antibiotic Resistance Fighter." It's in the April issue of Scientific American magazine and it's available at our Web site, www.sciam.com. And while you are at our Web site, check out the information on how to get a free preview issue of Scientific American magazine along with a gift, that's www.sciam.com.

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

Story number 1: Researchers have created transgenic pigs that produce heart-healthy omega-3 fatty acids.

Story number 2: Astronomers¹⁹ have detected an energetic outburst near the constellation²⁰ Sagittarius that they believe was caused by a distant galaxy²¹ in the midst of reversing the direction of its spiral rotation²².

Story number 3: A psychology²³ study found that if you think that another person is dishonest or immoral²⁴ it can affect for the worst your memories about the actual behavior of that person.

And story number 4: Older women who watch mostly talk shows and soap operas scored lower on tests of cognitive²⁵ skills than did women who watch other kinds of TV shows.

We will be back with the answer. But first, William Shockley shared the Nobel Prize in physics in 1956 and he later became a controversial, even despised, figure with his theories of eugenics and intelligence. Journalist Joel Shurkin has written a new biography of Shockley. I called Shurkin at his home in Baltimore.

Steve: Hey Joel, how are you?

Shurkin: Well! Doing fine. How are you out there?

Steve: Pretty good. So, tells us, first of all, for some of the younger people, maybe they haven't heard of William Shockley. Who was William Shockley?

Shurkin: Well! First of all, he was the co-inventor of the transistor²⁶, sort of revolutionized the world. Second of all, he was the founder²⁷ of Silicon²⁸ Valley. His company was the first Silicon Valley company. And third, he was involved in a dispute over nature and nurture²⁹ and intelligence and genetics and race and eugenics, and destroyed his life thereby³⁰.

Steve: Yeah! The second part of his life was really fascinating. It's like his whole life kind of just went off the rails. Let's go over exactly what he did in the later part of his life that made him so controversial. It wasn't just that he started to have these kinds of beliefs about race and about intelligence and he really acted on them.

Shurkin: Yeah! Well! He acted on them. He gave speeches on it. He got into debates on it. He did everything he could to publicize it. He called it dysgenics, which is the opposite of eugenics. He believed that the human race was de-evolving because the brightest people were reproducing at a lower rate than the un-brightest people. It's sort of reverse Darwinism. It was an argument that the scientific community did not want to hear and does not want to hear now. Nature-nurture debate is still extremely controversial and I am sure the book is going to raise hackles from one… to another country to the other. He was as politically incorrect as a human being could possibly be.

Steve: Well! It almost sounds from the way you said that as if you have maybe a grudging³¹ admiration³² for him. Is that going too far?

Shurkin: That's going too far.

Steve: Okay.

Shurkin: The problem with it is that some of things he said turned out to be true. Intelligence probably is, to an extent we don't know, inheritable. That turns out to be accepted science. What got him into trouble besides that is that he believed that the blacks scored 10 percent less on IQ tests as a group than whites did, and people did not want to hear that, do not want to hear that, and no one knows what to make out.

Steve: But he seemed to be pretty sure about what to make of it.

Shurkin: Yes! He was. He claimed he was not a racist³³, but after a while, you know, when you push somebody into argument they start getting more and more extreme and that's what happened to him. He started out almost reasonable, but by the time he was done arguing he was totally unreasonable³⁴.

Steve: And, he really spent the last years of his life completely….

Shurkin: The last third of his life was spent on this thought, totally destroyed his reputation.

Steve: He wasn't doing physics anymore, right?

Shurkin: Oh! No! He stopped doing physics a long time ago. When his Silicon Valley company failed in the early '60s, he stopped doing physics.

Steve: What was the name of that company?

Shurkin: Shockley Semiconductor³⁵. It was the first Silicon Valley company. Shockley was such an unpleasant person that his eight best employees left, founded something called Fairchild Semiconductor, and then several of them left and formed a little company called Intel. He could have been at least as rich as Bill Gates. He could have driven technology in them, the most influential³⁶ and important people imaginable, but because by this time he became such an irascible son of a gun nobody wanted to work for him or even be in the same room with him. A friend of his described him as having reverse charisma³⁷.

Steve: Reverse charisma.

Shurkin: He would walk into a room and you would instantly take a disliking (unclear).

Steve: So, what was it about Shockley that attracted you to him to the point where you wanted to spend the time that takes to write a biography of somebody?

Shurkin: I am not too great.

Steve: It's a good thing that Shockley didn't know you because he might have wanted to have you sterilized³⁸.

Shurkin: He wouldn't have let me interview him because I would have failed the IQ test, (laughs) which he allegedly gave every reporter who wanted to interview him, but turns out not to be quite sure, but almost. Shockley's life was a Greek tragedy without redemption at the end. It has got all the elements. Socrates easily could have written his biography.

Steve: Did you learn anything that really surprised you in the course of researching this book?

Shurkin: Several things. One was his influence on Silicon Valley. I did not realize that he was the reason why it's called Silicon Valley and not Germanium Valley for one thing. He is also the reason why it's in Northern California instead of Pasadena, which is another thing. He had that much influence on it.

Steve: Well! Silicon over germanium because that was the element that he realized was what you should be working with?

Shurkin: Yes! It was easier and more effective to be working on silicon than germanium. Mostly, the original work has actually been done on germanium and it wasn't until he decided³⁹ that he was going to build silicon transistors⁴⁰ that everybody else switched this world.

Steve: Joel, thanks very much.

Shurkin: My pleasure.

Steve: Joel Shurkin's biography is called Broken Genius: The Rise and Fall of William Shockley. It comes out at the beginning of June and it's available now for pre-order at Amazon and Barnes and Noble.

Now it's time to see which story was TOTALL…….Y BOGUS. Here are the four stories again.

Story number 1: Transgenic pigs make omega-3 oils.

Story number 2: Astronomers say an energy outburst as a galaxy reversing its rotation.

Story number 3: Believing somebody as a liar⁴¹ affects your memories of their behavior.

Story number 4: Older women who watch mostly talk shows and soap operas score poorly on tests of mental functioning.

Story number 4 is true. Reuters Health reports that older women watching soaps and talk shows scored lower on mental tests according to a study published in the March issue of the Southern Medical Journal. Of course, now that doesn't mean that these TV shows are dumbing it down and this is serious, it could be the other way around that having the poor cognitive skills might be what attracted, you know, watch those TV shows in the first place.

Story number 3 is true. If you think that somebody is immoral, your memories of that person's actions could be worse than if you think they are honest. That's according to a study in an upcoming issue of the journal Memory and Cognition. Psychologists told about 300 subjects a story about a guy who skipped out on his restaurant bill and they also mentioned the amount of the unpaid⁴² bill. Those who were told that the dine-and-dash guy was "a jerk who liked to steal" remembered the bill as being up to 25 percent more than what they had been told it was. Those who were led to believe that the man skipped out on the bill because he had gotten an emergency phone call recalled the bill as actually being slightly less than what they had originally been told.

And story number 1 is true. A new kind of transgenic pig produces the healthful omega-3 oils usually found in some kinds of fish. That's according to a study in the April 6th issue of Nature Biotechnology. Says Scientific American magazine editor in chief John Rennie, "If I can lower my cholesterol⁴³ by eating pulled pork sandwiches and bacon, I may weep with happiness." Pork, the other white fish.

All of which means that the story about an energy outburst in the constellation, Sagittarius being from a galaxy reversing its rotational⁴⁴ direction is TOTALL…….Y BOGUS. What's true though is that from our earthy point of view, the center of our galaxy, the Milky⁴⁵ Way is in the direction of Sagittarius and the Milky Way appears brightest there because that's where it's the most dense⁴⁶ without watching soap operas or talk shows.

Next up, Steven Salzberg. Dr. Salzberg is the director of the Center for Bioinformatics and Computational Biology at the University of Maryland. He is also a professor in the university’s computer science department. He has been talking lately about how we could probably put up a better fight against the flu by making some changes in how research results are reported and shared. I called Dr. Salzberg at his office in College Park, Maryland.

Steve: Dr. Salzberg, thanks for talking to us today.

Salzberg: You are welcome.

Steve: So, you want open or more open access to… is it avian flu data or the actual viruses?

Salzberg: Well! It's both, although my primary involvement has been with flu data.

Steve: And what's the current situation in terms of how open the access is? And why do you think that needs to be changed?

Salzberg: Well! There isn't any uniform policy, but it's normal scientific practice in many fields to collect data and analyze⁴⁷ it for some period of time while you work on your scientific paper and that period of time can be sometimes years. If you are not working in an area of research that's critical to human health, it probably doesn't matter, but in the case of the flu and avian flu, most recently, this is an area that is of critical importance with health. So, collecting samples and collecting data about the samples and then just sitting on them while you analyze them to your heart's content is not really acceptable in my opinion.

Steve: So, I have heard that there's a private flu database out there among a small group researchers. What is that all about and why does that need to be fixed⁴⁸?

Salzberg: Well! There is a database called the influenza⁴⁹ sequence database that I believe is maintained at Los Alamos by a group of researchers there and for some years now they have had an open part of it and a closed or private part of that database, and a small number of researchers have been allowed to have access, small number of labs have been allowed to have access to this private database and they deposit their flu samples in there and they can share data amongst themselves, but no one else gets to look at it. Some of the groups participating in this includes U.S. CDC and World Health Organization, the WHO, and these are groups that they do a wonderful job at protecting human health around the world in many different areas, but their mission really is to protect human health and they need to recognize that keeping a private database of flu samples is not the best way to serve that mission. I would like to see it opened up.

Steve: What specific recommendations do you have?

Salzberg: Well! Specifically, the agencies that fund researchers, most of the research including my own, is funded by the government. In the U.S., it's usually funded by the federal government. There is some state funding, but large majority of it is federal government. the National Institutes of Health being the biggest funder but in the case of the flu, the Centers for Disease Control also fund their own research and a little bit about that research, and other countries also have their own ways of funding things, typically government, and the researchers in their current model of working, they are not required to release their scientific data until they publish it. Even when they publish papers, they are not always required to release the underlying⁵⁰ data, but generally they want to wait at least until they get a paper because the currency of scientific research is credit, that is, credit in terms of recognition of your peers, your name on a prestigious⁵¹ scientific paper, that sort of thing. So, if the funders require you to release your data right away, then you do and we have a good model for that in the genome sequencing community, which I have been involved in for 10 years now. Most if not all large scale genome sequencing projects are funded by agencies that, now usually the NIH with the National Science Foundation, that require you to release your data immediately.

Steve: I was going to ask you if there were[was] precedence without the research materials but you basically covered that with the genome project.

Salzberg: Yeah! the human genome project established rules very early on that all the sequence data would be released right away. Now, in that case everyone involved knew that it was going to be several years before the sequencing was finished. So, to sit on the data for many years, which everyone considered that just to be unconscionable. But these days, a flu sequence only takes, you can sequence it very quickly that the delay is not finishing the sequence. It's a small genome. The delay is the amount of time it takes for a scientist to write a paper, which can take a very long time.

Steve: Whereas in theory, once you have the data, the sequence analyzed⁵², you could just pop it on the Internet.

Salzberg: Yes! And in fact that's exactly what we are doing in a project that I am involved in jointly⁵³ with the Institute for Genomic Research here in Rockville, Maryland funded by the NIH. We are sequencing thousands of flu islets. So far, they are all human, but we are now starting avian flu as well and as soon as these sequences finished, we put it on our own Web site and we also deposited it in GenBank for public… sequence depository that all researchers use.

Steve: And that's a personal decision that you made?

Salzberg: Well! It was a personal decision, but when we requested the funding from NIH, we said this is what we are going to do and NIH awarded the funding with this understanding. So, there is now over 800 flu sequences that have emerged from that project in just the last year and I expect that number to more than double in the next year.

Steve: Dr. Salzberg, thanks very much.

Salzberg: You are welcome.

Steve: There's a lot of interesting stuff about genomic sequencing the flu and related subjects on Steven Salzberg's home page. Just Google Steven Salzberg. That's Steven with a "v" and Salzberg is s-a-l-z-b-e-r-g.

Want to know what your child is really thinking? Leading scientists get inside the heads of youngsters in "The Child's Mind." That's an exclusive online issue available at www.sciam.com/special.

Well! That's it for this edition of the Scientific American podcast. Our e-mail address is [email protected]. That's [email protected], and also remember that science news is updated daily on the Scientific American Web site, www.sciam.com. For science talk, the podcast of Scientific American magazine, I am Steve Mirsky. Thanks for clicking on us.