IRA FLATOW, host:
This is TALK OF THE NATION: SCIENCE FRIDAY. I'm Ira Flatow.
A 31-year-old Atlanta man remains in isolation in a Denver hospital, where he is gaining treatment for a very, very dangerous kind of tuberculosis. It's called extensively drug-resistant TB or XDR-TB. Yesterday, doctors said they are going to perform surgery on Andrew Speaker to remove a tennis ball-sized piece of his infected lung.
Speaker is getting antibiotics, but the drugs really aren't enough because this TB has developed resistance to our latest line of antibiotics, a class of drugs that includes Cipro, and doctors don't have anything new to try on him. So even though we spend over $50 billion on pharmaceutical development each year, the best option for curing this infection is surgery. It's the same course of treatment we used before World War II, before the golden age of wonder-drug antibiotics. We've gone back to the future.
This hour, we're going to talk with one of the doctors at the hospital treating Andrew Speaker, and then we're going to take a closer look at our system for developing new drugs. Are we falling down on the job when it comes to treating infectious diseases? Why don't we have new antibiotics? And if you wonder these same things, give us a call. Our number, 1-800-989-9255, 1-800-989-TALK.
Let me introduce my first guest. Dr. Michael Iseman is the former chief of the tuberculosis program at National Jewish Medical and Research Center in Denver. That's the hospital treating the man with the drug-resistant TB. Dr. Iseman is also a professor of medicine at the Divisions of Pulmonary Medicine and Infectious Diseases at the University of Colorado. Thank you for taking time to talk with us today, Dr. Iseman.
Dr. MICHAEL ISEMAN (Former Chief, Tuberculosis Program, National Jewish Medical and Research Center; Divisions of Pulmonary Medicine and Infectious Diseases, University of Colorado): Thank you for having me, Ira.
FLATOW: Can you give us as little update on the status of the patient?
Dr. ISEMAN: Well, he is tolerating the medicines that are being administered to him. He is doing really as well as one could hope. It's a combination, I think, of the physical effects of his illness and the - I think - the unavoidable implications of his situation.
FLATOW: Is he getting the - what would be called a standard treatment for this type of TB?
Dr. ISEMAN: Well, it really isn't a standard. This is pretty much custom tailored for each patient and each individual's strain of TB. One of the advantages we have at our institution is our ever-marvelous laboratory that can test the particular strain of TB in the laboratory to find out which drugs are most likely to be active in this case.
FLATOW: In fact, your institution stretches way back in treating TB.
Dr. ISEMAN: We were part of the sanatorium movement of the 19th century. Before there were drugs, there was a widely held perception that going to the mountains for the sunshine and the fresh air would be curative.
FLATOW: Mm-hmm. Are you there?
Dr. ISEMAN: Yes.
FLATOW: And so you - that's why it's located up there in Denver, where you're in the mountains and sunshine.
Dr. ISEMAN: It was actually an industry. There were a number of TB sanatoria up and down the front range of the Rocky Mountains. Actually, historically, the first sanatorium was in Upstate New York in the - Lake Saranac, and it was a marvelous enterprise. But I think the notion that sunshine was helpful gradually caused the sanatorium movement to come West.
FLATOW: Did you have very much more in those days that you could offer a TB patient?
Dr. ISEMAN: There was a variety of remedies. George Bernard Shaw, in "The Doctor's Dilemma," written in 1902, talked about a huge, commercial system of quackery. Their desperate situations bred desperate acts or a number of things done to inform(ph) patients probably with little advocacy and potentially some harm.
FLATOW: Mm-hmm. How much does it cost now to treat Mr. Speaker and getting the special care that he's getting?
Dr. ISEMAN: The care of patients with drug-resistant TB is very demanding. The patients have to be isolated in an - in a particular room so they don't' spread it to others. They have to receive exotic second-line medications. And most of them end up going through surgery. As you and all of your audience know, surgery is really an extraordinarily expensive thing these days.
A few years ago, we calculated the average cost for our patients, and it - the actual charges were in the range of $180,000 per patient.
FLATOW: And surgery was not uncommon in the days before antibiotics, was it?
Dr. ISEMAN: The - there was a school of thought that either by collapsing the lungs, by putting air in the side of the chest wall or putting paraffin against the lung or actually deforming the ribs that we could compress the critical areas of tuberculosis. No one studied that systematically by modern methods we call randomized clinical trial. It was just the impression of doctors at the time that it was helpful.
FLATOW: Mm-hmm. And so how much of his lung, do you think, will have to be removed?
Dr. ISEMAN: Fortunately, it looks like a relatively small portion is involved. One of the modern tools we have allows us a much better view of the lungs. It's the computed tomographic scan or CT scan, and by that, we have a pretty good idea what areas of the lungs are involved. And the - our principle is to resect the minimal amount of tissue that's appropriate.
FLATOW: By removing this, do you prevent the spread or do you help the body fight the small amount of TB that you may leave in there?
Dr. ISEMAN: That's a great question. Our theory is based on the historical observation that in the areas in which there's gross disease, that's where the bacteria multiply rapidly. And our concern in doing surgery even though he's responding to his treatment is that if that area of multiplying organisms spawns organisms that are resistant to the few drugs we have left, we'll have no tools left to control his TB. And so the combination of medicines and removing the gross areas of disease, in our experiences, resulted in very gratifying high-cure rates.
FLATOW: Let me bring out my other guests, if you will, to talk more about why we don't have drugs to treat this problem. Dr. Michael Draper is the director of Anti-Infective Drug Discovery at Paratek Pharmaceuticals in Boston. And Scott Franzblau is professor at the University of Illinois, Chicago. Dr. Franzblau is director of the Institute for Tuberculosis Research there. Thank you, gentlemen, for being on with us.
Dr. MICHAEL DRAPER (Director, Anti-Infective Drug Discovery, Paratek Pharmaceuticals): It's nice to be with you today, Ira.
FLATOW: You're welcome. Dr. Franzblau, we've heard about MVR TB - how is that different than what we're - this kind of TB we're talking about today?
Dr. SCOTT FRANZBLAU (Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago): Yeah, MDR-TB is resists - is defined as being resistant to the two best TB drugs that we have, the two bust first-line TB drugs. That's isoniazid and rifampin. And that alone makes it, you know, difficult - much more difficult - than to treat, you know, your normally susceptible TB. The XDR, in addition to being resistant to the two best drugs, is also resistant to the best second-line drugs that we have including the fluoroquinolones - like, as was mentioned, Cipro in the beginning - and also one of the injectable antibiotics. These are either aminoglycosides or another class known as cyclic peptides. So this, of course, makes it even more difficult to get a cure.
FLATOW: Mm-hmm. Dr. Draper, you were on other drug-resistant diseases. Tell us what else is out there.
Dr. DRAPER: What else is out there in terms of drug-resistant organisms?
FLATOW: Besides TB. Well, besides TB, what other drug-resistant disease do you have?
Dr. DRAPER: Well, we have a real problem in our nation's hospitals and now in the community with drug-resistant staphorius, which many of the listeners may have heard of as MRSA. This is a serious problem within our nation's hospitals. We're developing a real problem with many of the gram-negatives, including resistant Pseudomonas and clepsiol(ph) that are resistant to the carbopetin(ph) class drugs that have been stalwarts(ph) and very important drugs in treating the gram-negative pathogens. So we are really starting to have a problem with drug resistance.
FLATOW: You know, what struck me when this gentleman was discovered to have this extremely resistant form, and when people were talking about how he was allowed to travel and to get on the plane, people were really upset that this man was travelling and moving around. And what struck me is that people weren't upset that there were no drugs able to treat him. Why were there no - here, we're crying, saying, how come we don't have any antibiotics?
Dr. FRANZBLAU: Well, for tuberculosis, there was really a perception for the last few decades that, one, this was no longer a - really an important disease in the world, and two, that it was extremely - there was no money to be made in this disease, which of course, drives the pharmaceutical industry's drug discovery programs. So we really had a lapse of several decades where there was no new drugs being discovered for tuberculosis. So we are left with the drugs that we discovered in the '50s and '60s and early '70s.
FLATOW: Mm-hmm. Does that bother any - either one of my other guests?
Dr. ISEMAN: It - not to sound cynical, but it's understandable, looking at the financial implications of new drug development. It is very difficult to justify or to recover the expenses in developing a unique drug targeted for TB. Part of the reason for that is that where much of the TB is in the world, they can't afford new and expensive drugs that are on patent. One of the things that happens as the consequence of that is that new drugs are just pirated, if you will, and produced in other areas without honoring patent rights, so a pharmaceutical firm can't recover its expenses. This is understandable, but it's understandable in both directions - why it's done and why pharmacists choose not to develop new drugs for TB.
FLATOW: And that's true of other infectious diseases too.
Dr. DRAPER: In some instances, yes, it is true in other infectious diseases. Although the infections - the resistant infections that I mentioned earlier, I think that there are, you know, developed markets in the developed countries and that pharmaceutical companies can enter those marketplaces, and you know, get a reasonable return for their investments.
FLATOW: Is there anyone, Dr. Draper, any company working on developing new antibiotics?
Dr. DRAPER: Working on developing new antibiotics? Well, yes, there clearly is. I mean, working on developing - if we stick with the topic of TB for just a moment - I think what you've seen for TB - and not just for TB, but for other what I'll call neglected diseases such as malaria - that there has been a real change in the way drug companies are going about trying to develop drugs for these. And I call these sort of public private partnerships, and Dr. Franzblau actually has experience with this. He's involved in one with a project between his own laboratory and the Global Alliance for TB.
And what's been done here is a situation where there are many good ideas that have been sitting on the shelf, and as Dr. Iseman said, there really isn't the financial drive to develop these good ideas further. So they have been sitting on the shelf for a period of time.
FLATOW: All right. Let me stop you there because we have to take a break, but I've - it's an important point. Let's go back to it as soon as we can when we come back. We're talking with Dr. Michael Iseman, Michael Draper, and Scott Franzblau. And your calls - our number, 1-800-998-8255. Stay with us, we'll be right back.
I'm Ira Flatow. This is TALK OF THE NATION: SCIENCE FRIDAY from NPR News.
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FLATOW: You're listening to TALK OF THE NATION: SCIENCE FRIDAY. I'm Ira Flatow. We're talking this hour about drug-resistant diseases including that really rare and deadly form of tuberculosis. My guests are Dr. Michael Iseman, physician at the National Jewish Medical and Research Center in Denver; Michael Draper, director of Anti-Infective Drug Discovery at Paratek Pharmaceuticals; Scott Franzblau, professor, University of Illinois, Chicago and director of Institute - the Institute for Tuberculosis Research there. Our number: 1-800-998-8255, and when I rudely interrupted, I think it was Dr. Draper, right? You were telling us about having to have special facilities, I think, to do this research.
Dr. DRAPER: Yes. And I was mentioning is that for years I think we've had a number of good ideas that's been sitting on the shelf. And those good ideas, there has been no ability to bring them forward because of uncertainty in terms of financial return. What's changed recently, though, is that there is funding now from groups such as the Bill and Melinda Gates Foundation that are opening up a pathway and to bring forward some of these good ideas. And I mentioned, you know, Dr. Franzblau, I think he probably could comment better as he's involved in one of these projects.
FLATOW: Dr. Franzblau.
Dr. FRANZBLAU: Yes. So the Bill and Emily - Melinda Gates Foundation routes their money through a group called the Global Alliance for TB Drug Development, and they will put together a group or support projects that involve both industry and, say, public sector labs such as ours. And therefore, they can make use of our specialized facility, so you need a special biocontainment lab to work with TB. And in big pharma, there are very few of these. In fact, there are only two which I know of. So if they do have interesting compounds that might be good for a disease like tuberculosis, we can put together a project where those are actually tested in a laboratory such as my own or a couple of the other academic labs in the United States that have these specialized facilities. In this way, we can move compounds further down the discovery pipeline.
FLATOW: Now, not to take it away from the Gates Foundation and the wonderful things they do with malaria and other kinds of diseases, but to depend on a private foundation to save us from tuberculosis - it just sounds like there's something wrong with that. I mean, you know, shouldn't we be - Dr. Iseman -should not our own public health officials be looking into this themselves?
Dr. ISEMAN: I'd like to - would make a point that the United States' share of research in tuberculosis for vaccine development and a new drug development is extraordinary given the fact that we have a tiny fraction of the world's TB. There were nine million cases last year - 14,000 in the U.S. - and yet we're probably providing 75 percent of the global investigations into TB.
So we shouldn't despair that our country is not really at the forefront. And it could be argued that it should be a governmental model. On the other hand, Rockefeller eliminated hookworm in the southeast United States through his private enterprise. And so it's - I'm not sure we have to be locked into a single model.
FLATOW: Though we have other - we have staphylococcus. Since strep - the kind of things that were also very dangerous, and it's more dangerous to be in a hospital than out of a hospital these days. I mean…
Dr. ISEMAN: That's arguably the truth.
FLATOW: You know? So shouldn't we spending money on those antibiotics as well?
Dr. DRAPER: Well, in those situations, I think we are spending money to - both in terms of basic research, which we need to continue supporting, and money is being spent within the pharmaceutical industry to tackle those problems.
I mean, it is true that there has been a scaling back of antibacterial drug discovery efforts in the last decade, but despite that, I think there are efforts that are ongoing - many among small companies such as the companies that I worked for that are trying to bring drugs to the market to address these other resistance problems.
FLATOW: Okay. Let's go to the phones. 1-800-99-8255 is our number. Let's see if we can go to phone calls and go to Wesley(ph) in Princeton. Hi Wesley, how are you?
WESLEY (Caller): Good. How are you doing?
WESLEY: Hi. Yeah. My question was just more generally about these drug-resistant strains - how much the guests think that overprescription of antibiotics is the problem in general, so not just with respect to TB, but I mean whether wether they think that prescription of antibiotics should be more tightly controlled and whether that would help to reduce the development of drug-resistant strains of these diseases.
FLATOW: Dr. Draper.
Dr. DRAPER. Yes, that is one of the things. I mean, I think we need to seriously not just develop new drugs, but we need to take care of the drugs that we have - prudent use of antibacterials as a former mentor or mentor of mine, Dr. Stewart Levi, would say. We need to look carefully at how we use these drugs and in what situations we use them. We also have a lot of agricultural use of these drugs at this point in time. And we need to look seriously about how we use these drugs on the farm. Should we be using them as growth promotants(ph) and putting them into feeds? So, yes, overprescription is part of the problem, but it's only a portion of it.
FLATOW: There is this - there is no limitation now on using antibiotics that let's say, for a disease and moving it into farm animals, is there?
Dr. DRAPER: There are regulations in place. The FDA does look at that carefully. And in fact, in the last year, they've taken a very keen interest in it. And in fact, they've recently - a drug was just denied approval for animal use based on the fact that it was thought it was too important for use in humans.
FLATOW: Could we not could create a class of drugs that can only be used in humans so that it doesn't get out and mutate in the system and become drug resistant?
Dr. DRAPER: Yeah. That is one thing we need to consider. Now, I think that's why the FDA is looking carefully at agricultural uses of antibiotics so that as new classes come along, we perhaps can first preserve these, you know, just for human use. But this may only delay the problem. It may not ultimately solve the problem. Resistance will inevitably come up to these drugs.
FLATOW: 1-800-989-8255. Vincent in Virginia Beach. Hi, welcome to SCIENCE FRIDAY.
VINCENT (Caller): Yes. Hello, Mr. Flatow. Hello, Doctors. How are you today?
Dr. ISEMAN: Good, thank you.
Dr. DRAPER: Thank you.
VINCENT: Great. You know, it's very a interesting panel. The panel is really interesting. But the question I had was, okay, doctors are going to operate on this gentleman's lung, and they're gonna remove pieces of it. Now, the question I was curious about is (unintelligible) in the army(ph), and we would have samples of the tissue - what are they gonna do with this tissue? Is this thing going to be whisked off quickly to the Centers for Disease Control, or are pharmaceutical companies going to be clamoring to get a piece of it to try and fix the strain? So just curious what would happen to that sample. Is it going to be loaded with TB?
Dr. ISEMAN: Well, we've been doing surgery now since 1983, and it evolved because of our recognition that with medications, we wouldn't get cures. And so our institution has a pretty good idea. When we send the patient to surgery, we've treated them with maximal antibiotics the number of organisms there at the nadir. The surgeons and the pathologists know what they're handling. We actually found, to our chagrin, that if we handle the fresh lung to fix it for pathological examination, it was a risk for the pathologist handling the tissues. So now, we embed it in formalin before we actually handle the lung. We'd been fortunate that our system has not resulted in any infections for the surgeons, the operating room staff, or others.
FLATOW: Does it come right out of the patient and go right into the jar?
DR. ISEMAN: It goes right into the formalin in the operating room.
FLATOW: Hmm. 1-800-989-8255. Does any of you gentlemen know how or where this might have originated, how it might have spread - the patient?
Dr. ISEMAN: That's a certainly an intriguing question, because there's not that much XDR-TB here in the United States. The individual in question here has travelled to Asia and Latin America, might well have acquired it during one of those trips. It's unlikely but possible that he could have been infected here in the U.S., however.
FLATOW: Mm-hmm. And so they are still looking for that source?
Dr. ISEMAN: Well, we may not find the source. What is going on now, there's a National Library in which we do fingerprinting of the different strains of TB/ And between fingerprinting of the genetic background of that particular group of TB strains and the drug resistance pattern, we might get a hit. We might find that there was an identical organism somewhere, and we might go back, like "CSI," and figure out that this must have been the source of infection. But I don't like our odds of ever really finding out where it came from.
FLATOW: How many people do we think are infected with this TB, and how many might not even know they have it?
Dr. ISEMAN: Well, the World Health Organization recently calculated from their surveys that there may be 30,000 to 42,000 cases of XDR-TB. That's one of the things that should give us all pause. This individual's here in the United States, a resource-rich country. He will receive these medications. He will receive surgery and he has a good chance of being cured. But for the patients around the world with XDR-TB, it may well be a death sentence.
FLATOW: Mm-hmm. 1-800-989-8255. And would it not be prudent or not - if statistically, let's put it - to expect that there might be other people who are carrying this around who don't know they have it and might be spreading it to other people?
Dr. ISEMAN: That's always the scenario that preoccupies us. The local health authorities as well as the CDC are doing what we call a contact investigation using other tuberculin skin tests or other tests to identify latent infections in this individual's contacts. If we found these individuals to be newly infected, we, however, would be in a dilemma because it's not clear what medicines we could give them to interrupt the transition from latent infection to active disease.
One of the things we're trying to do with the current strain of TB in our laboratory is to find out if there are medications that might be offered to contacts to abort the development of disease.
FLATOW: Dr. Franzblau, any comment?
Dr. FRANZBLAU: I think one thing that's important to realize is that, you know, these strains are around the world and have been probably for quite some time since we started using drugs to treat TB. It's a matter of recognizing that they exist, and occasionally, you know, we'll have an outbreak such as occurred in South Africa. I mean, we had an outbreak of MDR-TB in the early '90s in New York City. And then we really become aware as the public about how serious this can be. But certainly, people are dying continuously around the globe from drug-resistant strains in which there is not the facilities available to actually determine that this was resistant to all of these drugs.
FLATOW: 1-800-989-8255. Well, let's go to phones. Folks want to know about TB. Let's go to Ed in Frederick, Maryland. Hi, Ed.
ED (Caller): Good afternoon. Good to talk to you.
ED: My question has to do with bacteria becoming unresistant. You know, the antibiotics put a stress on the bacteria population. A few make it through, reproduce, and then you have a drug-resistant form. Is it possible - if you were to stop using a particular antibiotic for a number of years, basically removing that stressor from the environment - that they might eventually lose that drug resistance? And then maybe 10, 20, 30 years, you could start using it again?
Dr. DRAPER: Well, there's clearly some evidence in Europe that that is the case, that if you do stop using an antibiotic, you can restore sensitivity to the strains that are out there both in the community and hospital. That being said, what we do know, though, is that resistance mechanisms can tend to cluster together within the genome. They tend to be carried on on bits of DNA that we call plasmids. And - and you may get multiple resistance mechanisms that are together on one plasmid. So unfortunately, to stop selecting for a single resistance mechanism, you may have to stop using a large number of different drugs, because any one - use of any one drug would continue to select for a whole host of resistance mechanisms that are just being carried along because they are part of the, you know, same piece of DNA.
So it's an unfortunate, unfortunate situation. So the answer to your question is that it's a complicated one. There are some situations where yes, we can reduce the pressure and we probably can restore sensitivity, but there are others where we will not be able to.
FLATOW: We're talking about drug resistance this hour on TALK OF THE NATION: SCIENCE FRIDAY from NPR News.
Dr. FRANZBLAU: Yeah, if I may comment on that…
FLATOW: Yes, go ahead.
Dr. FRANZBLAU: …TB perspective. The situation with TB is a little bit different in that we don't have the clustering together of resistance such as what Dr. Draper mentioned for the bacteria. But the other situation we have is we probably don't have the luxury of having enough good, effective drugs that we could elect to pull one off the market for, you know, for a number of years. So in the end, it doesn't seem like a viable option at this time. Hopefully, sometime in the future, if we ever end up in a situation of developing a large number of very effective TB drugs, you know, this could be considered.
FLATOW: Are there any promising new drugs in the pipeline, and if there are, is there any way to prudently speed up their development in the testing phase, for example?
Dr. FRANZBLAU: There are - right now, actually, in clinical trials - there are three different classes of compounds with a total of about five drugs. Two of these are actually in TB-infected patients. Others are in the earlier stages of clinical development. One of them is - one class - I mean the fluoroquinolones which actually are already being used, they just now are being subjected to formal clinical trials to see how they might best be used - you know, are our most effective second-line drugs, and there are a couple of classes behind there.
I think there's a limit to how fast you can speed these up. I mean, they do have to go through safety evaluations and phase-one clinical trials where you actually see can patients tolerate them. Earlier in the drug discovery pipeline, all we can really do is try to put more resources into the process.
FLATOW: Well, would it help - speaking of resources - would it help, in the patenting of these drugs - that we allow drug companies to make more money back on these drugs than they normally would? That's why they're resistant is because they're not making a lot of money to allow them to make a bigger profit on it somehow. Or to have the, you know, the U.S. government guarantee. We talk about flu drugs and things. We guarantee X number of vials they would buy. Dr. Draper, how about that?
Dr. DRAPER: Well, I think that those - I mean, I think the first thing you mentioned, which is extension of patent life - that is something that Congress has used before to incentivize companies, pharmaceutical companies, to go into different areas of drug discovery. And I think it's one that's improved - has - it's a path that has proved itself to be successful and one that could be enticing to pharmaceutical companies. If you gave them additional life on the patents, I think they would be more likely to invest in anti-bacterial drug discovery.
The issue of whether or not, you know, the government should have - you know, open up guaranteed marketplaces - there may be a place for that, but it's probably best reserved for very narrow indications where you would only have, you know, several thousands of patients that you might end up using the drugs for. But I think patent life is a very viable option that we should consider.
You know, we need to think of these drugs as societal drugs. They're important to us as a society, and we should perhaps create a specialized class for them
FLATOW: That's a very good suggestion. We're going to have to take a break and come back and talk a little bit more about drug resistance and tuberculosis and your questions. 1-800-989-9255. Stay with us. We'll be right back.
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FLATOW: I'm Ira Flatow. This is TALK OF THE NATION: SCIENCE FRIDAY from NPR News.
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FLATOW: You're listening to TALK OF THE NATION: SCIENCE FRIDAY. I'm Ira Flatow. We're talking about drug resistance this hour and concluding with information about possibly - what do we do? Let me ask Dr. Franzblau. What do we do now that, you know, what do we do with these patients? How do they treat us? I mean, what do we do for them if we can't give them drugs? How do we detect or treat any other patients who might be having, you know, become infected with TB?
Dr. FRANZBLAU: Well, I think…
FLATOW: We need a net, we need to keep in the net closer to find these people?
Dr. FRANZBLAU: Obviously, detection is important in developing countries. I mean, most of these people are - never have drugs susceptibility tests done. In other words, they're diagnosed with TB and are treated with the standard regimen, the assumption being that, you know, they do have drug-sensitive TB. We really need to beef up the diagnostic capabilities in - around the world so that these patients can be detected early.
Very often, you know, we talk about the XDR strains…
Dr. FRANZBLAU: …being resistant to so many drugs, but this begins in time with strains that are just resistant usually with one or two drugs, and they develop the resistance sequentially as the patients go on additional regimens and then maybe don't complete their course or there's an interruption in drug supply. And the drugs become resistant when - the bacteria become resistant to one drug at a time. So if we detect them early and we take up the early levels of drug resistance, the resistance to one drug, then we can treat we can treat them appropriately - again, if there are drugs available.
But that diagnostic part is really important. In this country, it's very good. But globally, this isn't the case.
FLATOW: Gentlemen, we've run out of time. I'd like to thank you all for joining us. We got Franzblau, professor at the University of Illinois at Chicago, director of the institute towards tuberculosis research there; Michael Draper, director of Anti-Infective Drug Discovery at Paratek Pharmaceuticals; Michael Iseman, physician at the National Jewish Medical and Research Center in Denver, professor of medicine at the University of Colorado. Thank you all, gentlemen, for taking time to be with us today.
Dr. ISEMAN: Thank you.
Dr. FRANZBLAU: Thank you, Ira.
Dr. DRAPER: A pleasure.
FLATOW: You're welcome.