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Everything You Ever Wanted to Know about E. Coli, Part 2

Carl Zimmer continues his discussion of E. coli, the bacteria that are the subject of his new book Microcosm: E. Coli and the New Science of Life. Plus, we'll test your knowledge about the Nobel Prizes awarded this week. Web sites mentioned in this episode include www.carlzimmer.com; improbable.com; nobelprize.org

Author and journalist Carl Zimmer continues his discussion of E. coli, the bacteria that are the subject of his new book Microcosm: E. Coli and the New Science of Life. Plus, we'll test your knowledge about the Nobel Prizes awarded this week. Web sites mentioned in this episode include www.carlzimmer.com; improbable.com; nobelprize.org 

Podcast Transcription

Zimmer: Another thing about E. coli is that to understand what it means for it to be alive is to understand how it's alive with other E. coli. For a long time, scientists just thought about E. coli just as this little chemical factory. You just feed it and it grows and replicates, and it grows and replicates, and you look at the proteins that it uses to do all that and that's it. But if you actually look at all the genes in E. coli, a lot of them have nothing to do with that kind of process. They, for example, have genes to make signals that they can send to other E. coli. E. coli in a sense talk to each other and they use the information that they get from each other to make group decisions. So for example, when E. coli come into your body and settle down, they might start talking to each other and as a group decide to make something called a biofilm. So what they do is switch a bunch of genes to make this rare kind of glue substance and they start sticking together and they form what you can kind of think of a [as], sort of, a microbial city. It's got layers to it, it's got little troughs where food can flow through it, and it's a way for the bacteria to survive better than they could on their own because they are also shielded together in this biofilm. You even have E. coli that will kill themselves in the defense of their fellow E. coli. So what you have to imagine is you have two colonies of E. coli and they are both running out of food. You have been going for a while without eating maybe. They are starving [starting] to get in trouble, they are feeling stressed. There's a little food left. What happens is that a few of the bacteria in one of the colonies will switch on certain genes and make toxins, and they start making these toxins, and they swell up with these toxins. They can pump them out of themselves and get bigger and bigger and bigger and bigger until they explode and they shower toxins all over their colony and the other colony. Now the bacteria in their colony don't die because along with the toxin gene, each E. coli makes an antitoxin so they can basically knock out the toxin and they are fine. But the ones in the other colony don't make the same antitoxin, so they can't defend themselves, and they die. And so the survivors can then go and feed on the remaining food without the competition from this other colony. So to understand what it means to be alive, you really have to understand what it means to be in a society. So there's a whole field studying that called social microbiology. And of course another big thing about life is that it evolves and it doesn't matter if you're a human or E. coli, you are the product of evolution. Darwin only believed that you could study the effects of evolution because it was so slow. So for example if you [he] went to the Galápagos Islands and saw birds with a number of very different kinds of beaks that were adapted to different kinds of food, and he said, these I think, descend from a common ancestor. And it turned out if you look at their DNA they actually do, but you never imagine that you could see evolution happen in his [your] own lifetime. Well that's different now, and it's different thanks in large part to E. coli.

Twenty years ago, Richard Lenski at Michigan State started a very simple experiment. He started with one E. coli and he started 12 lines of bacteria that were genetically identical in that one ancestor. He put them in flasks and he will let them eat glucose for a day; he only gave them a little bit of glucose so they run out of their food by the afternoon and then the next morning, he would go to the flasks take a dropper, and take a little bit of that solution and start it in a new flask with a fresh supply of glucose, and then they run out of food in that flask and then the next day, he would repeat the process, and he has been doing it for 20 years. Along the way he has been freezing some of the bacteria. So in a sense he is creating this fossil record that [where] he has got his ancestors frozen, and he can thaw them out and then he can see how they compare to their descendants. And so he can see, well after, say, a 40,000 generations are there any differences, has evolution taken place? And it has. So, one particularly weird thing is that they are fat now. They are 50 percent bigger than their ancestors and Lenski isn't really sure why. But it's a clear-cut genetic difference between the descendants and their ancestors and just about in all 12 lines that's what happened. This is really what Darwin was getting at, what we call fitness, how fast organisms can reproduce under certain conditions, and as you can see, the descendants do a better job in this particular environment than their ancestors. So they can reproduce about 75 percent faster, and that happened because they mutated and natural selection favored certain mutations, and there are more mutations and more and more and more. And Lenski can actually now go in and see what are the mutations that had happened. Something actually happened recently that was particularly weird. E. coli as [a] species is defined in part by what it cannot eat. So for example, there is a molecule called citrate which is what gives lemons their flavor. E. coli couldn't eat citrate or at least they couldn't until something very odd happened in Lenski's lab. Citrate is in that broth that this scientist used to rear this E. coli, and one day Lenski and his students noticed something strange, which is basically that one of the flasks had gone very cloudy with a lot of bacteria; and when they realized what happened was, those E. coli were eating the citrate. They have determined that this is a genetic change that has happened, and so if you define E. coli as a species then what we may have here is the origin of [a] new species.

What's interesting is that they went back in the frozen fossil record, I was telling [you] about, they found exactly where this change happened, and it appeared that the citrate eaters started becoming more common and then rare and then more common again and then they took off, which suggests that there are a lot of mutations that took place to make this happen. And they actually rewound the tape, and they went back to that particular line of bacteria end evolved citric eaters all over again. The kind of research that Lenski is doing is important not just to answer some of the basic questions about life but to answer some important questions about our own health. E. coli and other bacteria can make us sick, and in World War II scientists developed antibiotics to kill them and it seemed like magic bullets. The problem was that the scientists discovered very quickly that E. coli and other bacteria were becoming resistant. They were evolving resistance because the mutants that could resist a little bit were doing better than the susceptible ones and over time, it became more and more resistant. So now today scientists are trying to develop new kinds of antibiotics to overcome this resistance. You know, they are trying to find these drugs that maybe bacteria have not evolved resistance to, and they found some really promising ones. For example, they found the [that] frogs in their skin made this new totally different kind of antibiotic and first it seemed like it was indeed the magic bullet that there was no way that bacteria could evolve resistance to it, but scientists decided to run [an] experiment where they exposed E. coli to a little bit of this frog drug and then a little bit more and little bit more, and sure enough the E. coli evolved resistance to it in the lab. So even before this drug makes it to the market, we already know that we have to be very careful in dealing with the evolution of resistance.

Another thing about life is that, as Darwin argued, life forms a tree. So he envisioned species branching of from each other through natural selection, and here is actually where those E. coli that make you sick come into the story. So, most of the strains of E. coli that you will encounter are perfectly harmless and you have got probably about 30 of them inside of you right now; but there are some that are very nasty. So these are the kinds that contaminate spinach and hamburger. Their name is E. coli 0157:H7 and when they get into you, what they do is they build a needle and inject toxins into your cells in your intestines and [your] cells form these bizarre pedestals almost kind of like this throne you are making for this bacteria that is making you sick. They then make your cells discharge lots of their contents—that causes diarrhea—they may cause bleeding, and they can also release toxins, and if they get in you blood stream you're in real trouble, you may have kidney failure or death. Actually, there are lots of different kinds of E. coli that can make you sick. This 0157:H7 makes the headlines, mainly because it's a problem in the United States, but in the other parts of the world there are strains of E. coli that still make children very sick, and they kill millions of children every year, and they have lots of different ways of invading our cells and manipulating them. One of [the] things that they have in common is this needle that I was telling you about. So scientists have looked at the DNA of these strains that cause disease, and the DNA of the ones that don't and where do they get, well they get a tree, a tree of life. And so they can see how bacteria have evolved from harmless strains into really nasty ones again and again and again. This has happened many many times. Also disease-causing strains have also become harmless as well. And this is happening right now, and it turns out that the bacteria that were found in spinach quite a couple of years ago were very different from the other forms of this 0157:H7. In fact they have got a whole bunch of genes that they can find in the other 0157:H7. It is not that these are different versions of genes; they are different genes. So how does this happen?Remember before, I was telling you about bacteria having sex and the fact is that bacteria trade genes a lot.

Now they might build one of those tubes I was telling you about; sometimes actually viruses can move DNA from one bacteria to another. They can do it to us as well. We have lots of vestiges of viruses in our genomes, about a 100,000 of them. So viruses are moving around and they are taking genes with them, and so you have a very strange thing happening with E. coli. Imagine that say you shook someone's hand and you got their genes for eye color, [all] of a sudden your eyes went from brown to blue. It sounds pretty weird, but that happens a lot in the microbial world, and it's the reason that disease forming strains of E. coli evolved, and it's also how resistance evolves. So, it's still true that life branches as a tree, but now scientists are really starting to rethink that a bit. So maybe it's more like a web than a tree. So along with the genes being passed down from parents to offspring, you have genes moving from side to side, because they don't just move between one E. coli and another E. coli;they move to another microbe that has been separated by billions of years of evolution. So, finally what I want to talk about is how E. coli can also help to understand how scientists are expanding our understanding of life today, because E. coli was the first organism to be genetically engineered. The first organism in which scientists went in and inserted genes that did not belong to its species into that organism; and as I talk about it in the book, genetic engineering has caused a lot of anxiety in part because people feel that it's not natural. You know you shouldn't be tampering with nature, you particularly shouldn't be blurring the species boundaries; as I have just shown you, there is lots of blurring of species boundaries out in the natural world, particularly among bacteria, and it has been going on for billions of years. So there may be risks to doing these things, but to say its unnatural is not a good argument. So, in early 1970s what researchers did was they took DNA from, in one case a frog, and they basically stitched it into a ring of DNA that could be put into E. coli and so now you have E. coli with a frog's genes in it,and so this raised the possibility, well, what if you would put in a gene that could make something really valuable? What, for example, if you could put in a gene for human insulin and it would start churning out insulin for you?Now at that time this created a big controversy as I mentioned. People were very worried that for example, E. coli would get into people's systems and it would create diabetic comas because it would be churning out insulin inside of our guts, and so on; and actually genetic engineering was banned in Cambridge Massachusetts by the local government because of these fears. Things have changed quite remarkably, so, you know, now people do actually get a lot of their insulin from E. coli. Insulin was actually the first big product to come out of genetic engineering in 1980 or so and now millions of people get their insulin from E. coli as opposed to getting it from the pancreas. But what's happening now is that scientists are taking genetic engineering to a new level and what they are doing is they are thinking about E. coli not as just this gene and that gene and that gene, but they are thinking about E. coli in terms of circuits of genes, like I was talking about before. So if you can add one gene to E. coli and have it churn out insulin, maybe you can create circuits of genes in E. coli and have it do things, have it respond to its environment in interesting ways, and so now MIT actually holds a contest every year where undergraduates come and try to fool around with E. coli to make it do something new and interesting; and a few years ago one of the winners was E. coli that's a camera. So what they did was they put into E. coli genes for pigment to turn it dark and they essentially linked up these pigment genes with light sensing genes, and so if you exposed a big plate of E. coli to a picture on your bright light, it would make its own picture. Scientists are now kind of going from these cute demonstration projects to what might eventually turn into real applications.

So, for example, at the University of California in San Francisco they are trying to engineer E. coli so that it can detect cancer cells, it can invade tumors, and then once it's inside they can release toxins; and so they are putting in all sorts of genes from other bacteria to assemble this, you know, this sort of synthetic E. coli that could become basically a cancer torpedo. There are actually a number of companies that are now using synthetic biology on E. coli and other microbes to try to make fuel. So, for example, there is one company called LS9 that has figured out to make E. coli make petroleum. You can just take this stuff and take [it] to [a] refinery and you get gasoline; some people have made E. coli that makes jet fuel and all you need to do to get these kinds of fuels is to feed it sugar; so essentially you are turning sugar into all these different products. This stuff is really interesting, I mean, it is really going to, I believe, is going to change the world dramatically; but I think also it's going to help us to understand that question I started out the whole talk with, which is what does it mean to be alive?We are making forms of life that are very different from anything that ever existed before. We are not just moving genes from species to species—scientists are also changing the genetic code of E. coli. So for example, all living things make proteins from these building blocks called amino acids. All of us only use about 20 or so of these amino acids even though there are hundreds that we could theoretically use. So why is that that we and elephants and blue whales and mushrooms all use the same basic set? Is it just a fluke or is there something that's superior about these so that evolution rejected all the others? Is it that you couldn't survive using other amino acids? Well, scientists have been trying to answer that question with E. coli. They have reengineered it so that it now can use these other amino acids—they are called unnatural amino acids—to build proteins. They have put in 30 different amino acids into E. coli and it does just fine. It just goes about its business. So that is one reason why NASA is quite interested in synthetic biology and in E. coli because it's going to help them to understand what they should be looking for on other planets; and how weird will life be out there, and, you know, what I am curious to know is that there was a saying, as I said before, "What is true for E. coli is true for the elephant"—is what is true for E. coli true for aliens? E. coli is already up in space. You knowit's up there in the space station, in the astronauts, and it turns out its falling around in the little beads of water; and when scientists actually get to Mars and look for life there I don't think they are actually going to find E. coli there, maybe a few got stuck on a probe and got killed along the way but it's possible that maybe they find something that's a lot like E. coli.

Steve: Carl Zimmer's Web site and excellent blog is available at www.carlzimmer.com. If you go there you'll find a link to his Scientific American article on evolution and cancer. It was included in the book, The Best American Science Writing 2008.

Now it's time to play TOTALL…… Y BOGUS special Nobel Prize edition.Here are four Nobel Prize stories; only three are true. See if you know which story is TOTALL…… Y BOGUS.

Story number 1: The announcement of the 2008 Nobel Prize in chemistry featured one of the Nobel spokesmen in Stockholm holding up a vial filled with E. coli.

Story number 2: The 2008 Nobel in economics went to researchers who discovered psychological mechanisms behind people's desires to purchase clearly overpriced goods and services.

Story number 3: The 2008 physics Nobel went to researchers whose work explains among other things that a tiny imbalance between matter and antimatter is why we are all here.

And story number 4: Part of the 2008 medicine Nobel was awarded to a researcher who showed that some cancer is really an infectious disease.

Time is up.

Story number 1 is true. They did wave around a vial filled with E. coli when announcing that the chemistry prize went to Osamu Shimomura, Martin Chalfie, and Roger TsienThey discovered and developed green fluorescent protein which is now used to light up cells making it possible to observe biological processes. The E. coli in the vial were carrying the protein gene and the entire vial glowed green when exposed to ultraviolet light.

Story number 4 is true. Harold Zur Hausen showed that certain strains of the human papilloma virus cause cervical cancer. He shared the medicine Nobel with Luc Montagnier and Francoise Barre-Sinoussi who discovered that the immunodeficiency syndrome now known as AIDS was caused by HIV.

And story number 3 is true. The physics Nobel went to Yochiro Nambu, Makoto Kobayashi and Toshihide Maskawa for work related to asymmetries in nature. For example, if a particle of matter always came into being accompanied by its doppelganger antimatter particle, they both blink out of existence, but for every 10 billion matter–antimatter particle pairs at the big bang there was one extra matter particle and that's why we are all here now.

All of which means that story number 2, about the economics Nobel going to studies of the psychology of paying too much is TOTALL……Y BOGUS. The economics prize in fact won't be announced until October 13th; however, research demonstrating that high-priced fake medicine is more effective than cheap fake medicine did win the 2008 Ig Nobel Prize in Medicine. For more on these spoof Ig Noble prizes go to www.improbable.com, and for more on the real Nobel Prizes check out our Web site www.SciAm.com. We have breaking coverage all week. Also check out the official Nobel Web site: www.nobelprize.org.

(music)

Well that's it for this edition of the weekly SciAm podcast. Visit http://www.sciam.com for all the latest science news, blogs and videos and check out the new weekly podcast 60-Second Earth hosted by David Biello. For Science Talk, the protracted weekly podcast of Scientific American, I'm Steve Mirsky. Thanks for clicking on us.

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