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Return of a Killer: Tuberculosis in Russia

Veteran journalist Merrill Goozner, director of the Integrity in Science project at the Center for Science in the Public Interest, discusses his series of articles for SciAm.com on the rise of tuberculosis in Russia. Plus, we'll test your knowledge of some recent science in the news. Web sites mentioned in this episode include www.gooznews.com; www.snipurl.com/goozner

Uncertain

Veteran journalist Merrill Goozner, director of the Integrity in Science project at the Center for Science in the Public Interest, discusses his series of articles for SciAm.com on the rise of tuberculosis in Russia. Plus, we'll test your knowledge of some recent science in the news. Web sites mentioned in this episode include www.gooznews.com; www.snipurl.com/goozner

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Steve: Welcome to Science Talk, the weekly podcast of Scientific American for the seven days starting August 27th, 2008. I'm Steve Mirsky. Tuberculosis isn't back because it never really goes away. We have a series of Web articles up this week about the savage rise of TB in a multidrug-resistant form in Russia. They were written by veteran journalist Merrill Goozner. He was the chief Asia correspondent and chief economics correspondent for The Chicago Tribune. He is now the Director of the Integrity in Science Project at the Center for Science in the Public Interest. I called him at his office in Washington, D.C.

Steve: Hi Merrill, great to talk to you today.

Goozner: Pleasure to be with you.

Steve: This is an incredibly ambitious package that we have up on the Web site that you've pretty much done in its entirety. First, tell us what we are doing in Siberia.

Goozner: Well, I was asked to go there by Scientific American as part of a, sort of a, planned tour that had been put together by some nonprofit organizations that wanted to show off their efforts over the last decade in improving the way tuberculosis in general and in particular drug-resistant tuberculosis, multidrug-resistant tuberculosis, is being treated—in a corner of Siberia, where they thought it was a good model for what could be done around the world. Now of course, you know, there were several journalists on the trip and Scientific American paid for the whole trip. But after they took me out there, I had been a foreign correspondent in the past when I was working for The Chicago Tribune and hadn't been in Russia since the 1992 and even then it was in the Russian Far East, so it was interesting to return to the country almost two decades later and see the remarkable economic change that had been underway, but also many of the social problems that were still there.

Steve: Now, TB was not a problem of this magnitude the last time you were there.

Goozner: Well, you know, it was just at that point when Soviet communism had fallen, Boris Yeltsin was president and, you know, a new democracy was being born in Russia; at least that was the way it was being portrayed. But the transition from the old system to the new system was very rough and it was right at that point where the old economy was collapsing and the problems that came from that had not yet emerged but would within two or three years after I was there. In particular lot of people lost their jobs, there was a huge increase in crime, unemployment. I guess a better way to put it is unemployment and then the things that rose from that—crime, drug abuse, IV drug use, and AIDS epidemic and, of course, a tuberculosis epidemic. The prison population in Russia soared in the years after the fall of communism. Well over a million people ended up in jail. They are now down to about 75 percent of that as the economy has improved, but it was really a fast growing situation in those days, and then really by the middle of the '90s, they had a full-blown tuberculosis epidemic, but really which is coincident with poverty. Tuberculosis in the end is a disease of poverty and stress and it emerged in full force from the deteriorating social conditions, especially in Siberia and the Russian Far East.

Steve: Now Siberia and the Russian Far East are, you know, are fascinating in its own right, but it's also just a, kind of, case study, because this same kind of thing does happen anywhere in the world and can happen anywhere in the world. I mean, here in New York City, we saw a big comeback by TB and multidrug-resistant TB in the mid '90s as well.

Goozner: Just as in Russia, the epicenter of the epidemic was in the prisons. It sort of was its starting point. You have a lot of people all of a sudden in crowded condition[s] who were undergoing tremendous stress. One thing people don't realize is that a third of the world's population has what's called latent TB in them. But their immune systems have combated it successfully on their initial infection and it basically stays submerged within your body. If you have it, you can for [your] entire life. But what happens is that if you're under tremendous stress, poor nutrition, you know, your immune system becomes weakened and it can emerge again and become a virulent infection, and that's what happened in Russia. And there is some thought that when this emerged in the New York City prison system in the mid '90s, that it in fact had been introduced there by some of the Russian population that had left the former Soviet Union, wound up in New York. There is a very large Russian population in New York and that some of those people ended up in the prison system and just as it spread a plague in Siberia it spread it in New York City. The pioneering work of—who is now the Health Commissioner—Tom Frieden was very successful in stamping out and showing that you can in fact treat tuberculosis and some of the techniques that he used there were later transferred back to Russia by some of the NGOs that we visited there.

Steve: That's fascinating. I had never heard the connection before between the Russian outbreak and the New York outbreak. I thought the New York outbreak was homegrown and it may be, but it is a really interesting theory that the two are intermittently connected. Tell me about the kind of treatment that you have to perform. It's incredibly labor intensive.

Goozner: Tuberculosis was, you know, if you were to go back into the 19th century and the early part of the 20th century it was sort of like cancer was today. There was a kind of almost like mythology around the disease, almost a romance around it.

Steve: Yeah, La Boheme, it's a romantic disease but it is nothing like that in real life.

Goozner: Right. And the age-old scourge, mankind thought there was this miraculous cure that emerged in the late 1940s when Dr. Selman Waksman discovered streptomycin—there was a cure, it was thought, for tuberculosis. But what was rapidly discovered literally within a few years of the introduction of streptomycin to treat tuberculosis was that TB had the ability to mutate and or it will to a resistant strain that would quickly become dominant; and they would therefore the drug as a single drug was not effective. And over the years, tuberculosis became one of the first diseases where it was widely recognized that you had to use multiple antibiotics in order to cure [it] and it is just a question of statistics that if you hit an organism in two, three or four places at the same time, it becomes almost statistically impossible for a mutant to survive that kind of environment. So, tuberculosis became a disease that you had to treat with multiple drugs and the World Health Organization by the 1980s had adopted this as its primary way of treating tuberculosis. It's called Directly Observed Therapy and—it's called DOTS—and the reason why it had to be directly observed is because you had to hit tuberculosis with multiple drugs all for a long period of time, about six to nine months; it is a very relatively slow-growing organism. It only reproduces once a day so that you have to, you know, some of the drugs only hit it at the point at which it is reproducing and then, of course, they were like, as we talked about earlier, latent tuberculosis deep within the lungs. Very often that, you know, would take a while before the drugs can hit them at a point at which they will be vulnerable and so this became the recommended therapy, Directly Observed Therapy. Well, as you can well imagine in many settings in the world, enforcing that kind of regimen over that longer period of time, taking the same drugs everyday, some of which have nasty side effects, for six to nine months, there was a lot of breakdowns in places. And of course what happens when that occurs is that the resistant strain with the longest life in those particular bodies become dominant and then you have what is called multidrug-resistant tuberculosis; and that, of course, is with the new programs coming where there is now new antibiotics, some of the fluoroquinolones get added to the older regimens or older antibiotics and what you have is treatment for up to two years, again Directly Observed Therapy, everyday to close to two years in order to wipe out multidrug-resistant tuberculosis We have this image in our minds that MDR-TB, as it's known, is a worse disease than TB. That's not really the case. They are really the same disease. It's just that they had become much harder to cure, and of course tuberculosis will kill you if you do not successfully treat it. And so that became the sort of goal of these nonprofits that were doing work first in Peru, like Partners In Health at Boston, which is a very famous one run by Paul Farmer; he went into a low-income setting. The first case, that was Peru, and they said, you know something, if you're going to tackle the tuberculosis epidemic in this country—which means treating the vast majority of people with that six to nine month therapy or Directly Observed Therapy with four drugs—then you really have to create the infrastructure to treat those cases that have already failed the multidrug-resistant tuberculosis; that if you build that kind of system that can deliver that, you will get the others, too. And that's what they tried in Peru with some success. And that's the system beginning about a decade ago they exported into Russia, because in Russia you had some people, like people we visited in Tomsk which is a province in the Central Plateau (unclear 10:40) where the public health authorities there had a huge outbreak in the prison but they were open to new ideas. They were not wedded to the old Soviet style of centralized medicines, which was very dependent on a lot of operations—it was almost idiosyncratic in the way they used drugs—but Russia under communism had pretty much gotten their tuberculosis under control and it was only with the fall of communism that they had this huge outbreak to which they really needed much more public health–oriented approaches than the, kind of, idiosyncratic approach that they had in the past. And so what they did then was

itthat they [started] working with Partners in Health, they said, "Okay, let's try this DOTS approach and let's try this DOTS-Plus approach," in other words, going the full two years with the MDR-TB. And if we institute that kind of system we will be getting all the people who are sick and therefore we won't be getting reintroduction or that much reintroduction back into the community. If we are successful,andthat will be able to damp down the epidemic. It will be a wonderful story if I could tell you now that they have been tremendously successful. In fact in the last two or three years, we've begun to see a reduction in the total amount of cases in Tomsk province and, you know, is this because the economy is improving? Is it because they are treating it better? They are certainly treating it better. So you like to think that that is part of it, but there hasn't been the really sophisticated studies that you would need to do to, sort of, say that the public health approach that they have introduced there was really the factor. So it is important to remember that when economies improve, public health problems tend to diminish like a tuberculosis outbreak; and in the last three or four years, especially with the rise in the price of oil, the Russian economy has been improving quite a bit. And we saw that when we were in Tomsk there were a lot of cars on the street, there were a lot of stores that were opened. There seemed to be a much higher level of prosperity—at least according to the people, I wasn’t there six to ten years ago—but to the people I talked with there said that the economy was much better today than it had been in the fairly recent past.

Steve: I just want to reiterate Directly Observed Therapy or DOT requires somebody to actually watch the patient take their drugs multiple times a day. It's incredibly labor intensive.

Goozner: Exactly. It's a system that really requires the hands-on approach by people working in the health care system and they have created a very sophisticated system. They have actually people who, you know, many of the people are alcoholics living in very low-income housing projects, IV drug abusers. We are trying to get their lives together and they have actually even created a system which they call Sputnik, where a driver and the nurse will actually go to the homes everyday of the people who they are treating for MDR-TB and make sure that they take their drugs.

Steve: Because people don't like to take these drugs necessarily everyday for months and years.

Goozner: Well, two things, there is two reasons to that. One is the drugs have some side effects. Some of the antibiotics[' side effects] are well known: You know, they give you bad dreams, hallucinations, and, you know, it is not universal but there is a percentage of people who are more affected in that [it's] very difficult to keep down for some people. But just as importantly when you are successfully treating tuberculosis, you are not sick for six to nine months. You are only sick, you know, your disease becomes your sputum. Your ability to pass it to other people, the bacterium load goes down so low after the first few months that you are sputum negative, in other words you are not even infectious anymore. So you don't have symptoms of the disease—either you are not coughing up blood or hacking the way that you would with tuberculosis when it was really active and raging within your body. So unattended you might think, "Hey, I am cured; why should I take all these drugs or all these side effects for another four months or nine months?" And a lot of people would do that. That's why the preferred way of treating this is called Directly Observed Therapy—[it's] hands on, very labor intensive as you said to make sure that these people wipe out that disease inside them.

Steve: And Paul Farmer has had a great deal of success and he is an amazing guy, but also in Haiti I believe with DOT and HIV

Goozner: Exactly, yes, and you know Paul Farmer and Partners in Health is the group who have been working in Tomsk to set up these programs. We interviewed a number of people there, not that they have a very important philosophy when they go out there. Their feeling is that we are there to advise and it's really that we have to build a local infrastructure and give them the ability to do this. You can't rely on the kind[ness] of strangers for ever. You have to build a local infrastructure for delivering this kind of healthcare if it's really going to succeed over the long run.

Steve: Yeah, you have, your neighbor comes over in some cases to make sure that you are taking your medications.

Goozner: That's right. We actually saw a case of that in a rural housing project in Russia, where an elderly woman has had her tuberculosis cured and it was somebody who was in the building next door and they actually had a very important principle, which is the easiest thing you would say, you just appoint some family member to do it; but they say "No you can't do that," they don't allow family members to do it. Because it's very easy for like a brother or a son to [say]

tell, "Mother, don't bother me anymore, get out of here, I don't want to take those. You know, you could almost forbid family's spat; so they make it actually a requirement that a neighbor do it rather than somebody who is inside your own family.

Steve: Now do the public health officials, or the public health officials know, but do the other political officials understand that the very conditions that, I am not even talking about the economic conditions, but just the structures that incarcerate people, the crowding, all of that contributes not only to the transmission of the disease but actually to the evolution of the disease?

Goozner: Well, I think they understand it, but you know when we were dealing, we did visit a prison system there and I think that in the prisons you have to remember that these are not people that the society looks on with great fondness. If you have been sent to prison, like in any society, you are an outcast, you've been cast out of society; and so while they recognize it from a public health point of view, it's not like they are being given the resources to set up some kind of spa facilities. And so it's on the one hand you could say, yes when they put people who are infected with multidrug tuberculosis in the same ward together, they isolate him from everybody else but they are all in there together you said, it might got to you, you could have transmission and retransmission between each other, sort of like a colony for breeding.

Steve: It's an incubation center.

Goozner: Exactly and you got to realize, "Well, but look at what they have actually

done[gone] though." They have isolated them; they are all being treated with the drugs. There are cure cases that are taking place when they become sputum negative. They get moved out into another center where they're not being exposed to the other people who are still sputum positive. So they have really put in place a system where, given the limited resources, they are doing the best that they can, but you know in an ideal situation, that's not how you would treat it.

Steve: No, and especially a prison or a hospital has a semi-permeable membrane. There are people coming in and out of that place all day and some of that multidrug-resistant TB can get out into the general population through a guard or a cook; and so it's in everybody's enlightened self interest to make sure that the people in those situations get treated as much as possible.

Goozner: And of course that was one of the most tragic stories that we saw there. We actually also visited the tuberculosis sanatorium which was run not as a prison system hospital, but, you know, where the tuberculosis hospital for the entire province, where if you were sent if you got tuberculosis until you were sputum negative then you can go back into the community; and we saw a young girl who had what is called XDR tuberculosis—extremely resistant tuberculosis, which means that she failed the drug for multidrug-resistant TB. What happened was, she was only like 22-years-old and she has been there three years and she had had half of one her lungs removed already in an operation. What happened to her? She lived in a housing project. A man got out of prison. He had been, sort of, the first anecdote of our first story. He had been in prison. He had gotten tuberculosis. He had been cured. He had gotten it again. He was taken to regimen again but his term was up. He was free to go. When immediately he got out of prison, he stopped taking the drugs and of course the disease that came back was multidrug-resistant. A similar situation, a man got out of prison, he moved into her housing complex after getting out and the multidrug-resistant tuberculosis came raging back in him and he spread it to her. So her initial infection, you know, she could have caught it in the hallways wherever and she originally got multidrug-resistant TB while she was young rather gradual[ly]. She couldn't keep the drugs down. She was constantly vomiting from the side effects and as a result she went off therapy. Even though she was in the hospital and ended up with extremely resistant tuberculosis and it was taking them three years. But to get to the [broader]

borderpoint that you raise when you asked the question. Exactly, these places are incubators of plague, the prison[s]. People are going in and out of the prison all the time. They return back to society and the returning back to the society that Russia, especially out in Siberia, parts of it are, you know, what you would call, you know, second world and it's not the extreme poverty of the African nations or some other parts of the world. It's not third world, you know, the traitors of the Soviet system have left pockets of Russia with extreme poverty and there were parts of this town where we worked, Tomsk, that certainly fell into that category.

Steve: And if memory serves, I think we have over two million people incarcerated in the U.S.

Goozner: That's right. We have a population that's significantly larger, you know, one-third larger, but you know our population per capita is probably the highest in the world or among them.

Steve: The prison population?

Goozner: Prison population.

Steve: And so it's a condition that is just below the surface at all times all around the world and this can happen anywhere.

Goozner: Absolutely.

Steve: This is a fascinating package; it's up on our Web site. Let's take just a couple of minutes. You are the author—the book came out a few years ago, The $800 Million Pill—and while we have you here, tell us a little bit about that book.

Goozner: Well, it came out in 2004 and it was an effort to look at the drug development process in a, sort of, holistic way to look at where the sources of innovation were in the pharmaceutical industry and the biotechnology industry and, you know, what were the real drivers of that. Is it money? Which is what we all so often hear, it cost[s] $800 million to develop a new drug. What I tried to point out in the book, by looking at a whole series of stories that some of the more innovative drugs that come out over the past quarter century. This is to say that really pharmaceutical innovation, biotech innovation, is a product of science. [A] lot of it funded [is] in the public sector and the interaction of science with public health need and sort of devoting the societal resources and intellectual energy to sort of come up with new approaches to diseases that are the really serious things that we face as a society. It doesn't guarantee success but certainly the idea that you can simply pour money into a disease stage and somehow get new drugs out that would cure it at the bottom of some process is really not the way drug development happened over the years. And the book is a way of trying to put the third dimension into a debate over the cost of developing new drugs that I found all too often was lacking in public discussions about the issue.

Steve: And the book also points out just how many drugs actually are discovered, because lots of them are natural products in our government labs or in our government-funded labs.

Goozner: Absolutely. You know, it was much more true if you look back, you know, say before 1990 or so, but in the last two decades we've had a much higher emphasis on the private sector being the primary driver of drug innovation, and I think one of the great iron[ies]

yisthatitisn't really pointed out is that as we have shifted more to a private sector emphasis in bringing new significant drugs to market, the number of new drugs coming being approved by the FDA have steadily fallen; and, in fact, last year was the lowest level in several generations. So I think recent experiences suggested that that when you allow money to drive the process rather than science and public health need, you can often wander into blind alleys; and it's because of the marketing needs of those organizations. "Hey, they arepoor[for-]profit companies. That's what they are there to do with this is to make money. That's their primary obligation [to] the stock holders. But as one of the people that I quoted in my book pointed out, when you're looking at the market to tell you what to do, then it's by definition not innovative, because the market is always about whats already exist[s], and to find what's really needed you really have to be much closer to the bedside, much closer to the public health needs of the given society. We could, the drug industry if it wanted to, could be developing drugs, new and better antibiotics for tuberculosis for instance, but it doesn't because the market for those drugs is too small for them to really devote significant resources. And that's why you have so many nonprofit groups that have sprung up in the last 10–15 years, many of them funded by the Bill and Melinda Gates Foundation and to a certain extent multilateral organizations to develop new drugs for what are called neglected diseases of the developing world. There may not be a market, but definitely [there] is a social need and given resources, not the level of resources that industry would spend on a new drug, but a sufficient level of resources, it's possible to come up with new drugs, new vaccines, for many of those diseases and there is thousands of scientists out there working on it, and of coursethe poorestpart of the series on tuberculosis takes a look at some of those efforts.

Steve: Now to mention the market does not take into account the societal economic cost when one of the diseases breaks out and is not treatable.

Goozner: That's right.

Steve: This has been great talking [to you]; I really urge everybody to read the report on our Web site and Merrill thanks very much.

Goozner: Thanks for having me.

Steve: Merrill's articles and slide shows are all available at www.SciAm.com. Also check out his blog at www.gooznews.com.

(music)

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: New higher incarceration levels account for 60 percent of the increase in TB in post communist European countries.

Story number 2: Cows apparently have the ability to sense the Earth's magnetic field.

Story number 3: Neandertal stone tools were inferior to Homo sapiens' which could be why Neandertals went extinct.

And story number 4: Ear infections in infancy may be linked to adult obesity.

Time is up.

Story number 1 is true. A study just reported in the August 26th edition of the Proceedings of the National Academy of Sciences finds that the rise in prison populations in post communist countries accounts for 60 percent of new TB cases as well as a significant share of multidrug-resistant TB.

Story number 4 is true. Chronic ear infections in infancy may be linked to adult obesity. Because ear infections can damage a nerve that passes through the middle ear and controls taste sensation, which may intensify the desire for fatty or high-calorie foods. The study was announced at a meeting of the American Chemical Society.

And story number 2 is true. An analysis of Google Earth images finds that most cows stand aligned with the Earth's magnetic poles. We milked this story further in the August 26th episode of the daily SciAm podcast, 60-Second Science.

All of which means that story number 3 about Neandertal stone tools being inferior to Homo sapiens is TOTALL....... Y BOGUS. Because a new study in the Journal of Human Evolution finds that Neandertal tools were every bit as good as our own. Although nobody had yet invented bits.

(music)

Well that's it for this edition of the weekly SciAm podcast. Visit www.SciAm.com to check out Merrill Goozner's reporting on TB from Russia. You can write to us at podcast@SciAm.com. For Science Talk, the weekly podcast of Scientific American, I'm Steve Mirsky. Thanks for clicking on us.

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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.

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Return of a Killer: Tuberculosis in Russia