HIV’s “Tireless Warrior,” Anthony Fauci, Calls for Transformation of TB Research

Xconomy Seattle — 

Anthony Fauci is known around the world as a leading scientist and advocate, starting in the early 1980s, for research to fight HIV. The Voice of America once called him a “tireless warrior” for the cause. Now, Fauci says, biologists need to channel their creative energy to fight another deadly bug that has been around for centuries and rarely makes headlines—tuberculosis.

Fauci, 68, has been the director of the National Institute of Allergy and Infectious Diseases since 1984. This division of the U.S. government has a $4.7 billion annual biomedical research budget, which happens to be a lot more than the Bill & Melinda Gates Foundation gives away every year. So people listen carefully to what Fauci has to say. He delivered a high-intensity call to action yesterday to a crowd of 250 global health stars at the Pacific Health Summit, and I followed up with him for an exclusive interview.

First, a quick reminder of why anyone should pay attention to TB. It’s a contagious bacterial infection, and kills an estimated 1.7 million people a year worldwide, ranking it right up there with the world’s biggest scourges, like HIV and malaria. Yet it’s basically been treated like a research backwater for too long, Fauci says. The state of the art is depressing. There’s no vaccine. Diagnostics are lousy. The standard course of therapy—which has seen no improvement in 40 years—involves four drugs that must be taken daily for six months. Fail to comply fully with doctor’s orders, and you increase the odds of developing drug resistance, making it harder to treat.

Incrementalism in this field won’t cut it—a bigger transformation of TB is required to get serious about the disease, Fauci says. Here are the edited highlights of our conversation:

Xconomy: Why has TB been on the back burner of research priorities for so long?

Anthony Fauci: When you think about how basic and applied research drive a particular field, a lot of it has to do with the interest and energy of investigators who get involved in the field. They see it as an opportunity for them to make a contribution, as well as to advance their own careers.

TB has suffered a lot because of its own success historically. There were some blips when TB rebounded in the mid-80s and early 90s, and most recently with the serious issue of multidrug resistant TB and extensively drug resistant TB that has sort of rekindled interest. But most young investigators have not seen, with some exceptions, a career in research of TB as something to pursue. A lot of the transformational research from the past few decades, from the end of the 20th century and early 21st century, in the arena of systems biology, genomics, and all the other -omics fields, and all sorts of host-pathogen interaction study, has really passed by TB research.

The point I made in my talk is we’re starting to see a rekindling of some effort. We are really going to have a research agenda, and have research play a role in what is a very broad, heterogeneous, comprehensive approach to TB control, of which research is only one element. We have, in our possession, many of the tools if properly implemented, that could go a long way to control TB, including MDR and XDR TB. But we don’t have as robust a toolkit of interventions such as diagnostics, therapeutics, or vaccines that are 21st century-style, not the old ones that once seemed to fit the bill. What I was calling for is that the biomedical research community, with help from funders, and help from people who show leadership in that arena, is to look upon TB research in a more transformative way. That’s opposed to an incremental way.

Yes, it’s true we do need an additional drug here or an additional vaccine here. But we also need to understand some of the complexities that we never even bothered to look at with TB. Because historically, in the best of all worlds, we had curative drugs, and a diagnostic—antiquated as it was. Under the best circumstances, you could cure the disease. We never really catapulted TB research into the arena for highly sophisticated questions that we can ask and answer right now. So, despite the fact that we have a long way to go in implementing the tools we already have, if you really want to get a sustained control of TB, you will have to get the kind of diagnostics that you’d expect in the 21st century. You need a whole new way of looking at treatment. It’s not just a matter of adding another drug to the regimen, or subtracting one here. You have to look at the comprehensive package of the regimens we use. Then we have to understand host-pathogen interaction if we’re really going to get a vaccine that’s highly effective, safe, and could have a major impact. All of those things will come from a robust research agenda that’s sustained, and that involves young people with new ideas, who see a career in research as an opportunity to not only make a contribution to global health, but also will be exciting for them as a career.

X: You also mentioned there has been a big leap ahead in resources put toward this disease since you’ve been around at NIH. How big?

AF: When I started in 1984, the fiscal year TB resources from NIAID was $665,000. Now, NIAID supports over $130 million a year of TB research. Granted, that is over a 25-year period. But if you look at the relative increase of TB research over the last few years, comparing it to the overall flat NIH budget, it is clear that we have preferentially, with a high priority, put our limited resources on TB.

I have to underscore the resources are limited. Even though the NIH budget is a robust budget, it’s $30 billion, and we just got an additional $10.4 billion stimulus package, the budget for NIH over the last several years has barely, and in fact, hasn’t kept up with inflation. So despite the flattening of the NIH budget over the last five years, following its doubling at the end of the 20th and early part of the 21st century, despite that, we have still preferentially grown tuberculosis research.

X: So imagine I’m a young investigator. Tell me why I should get into this? What’s intellectually exciting?

AF: When I talk to young people, and the people who work in my own laboratory, the two things that drive them are this. Number one, what is the public health issue involved? Is it an important problem? You don’t need to be a genius to figure out that when one-third of the world’s population is infected—and it’s responsible for 1.7 million deaths, and 9 million new infections each year—that this is a really big public health issue. So it has relevance.

The other thing is, what is the scientific opportunity? Let’s focus on that. The point I was making in my talk is we have not even begun to explore the extraordinary scientific opportunities. The TB research agenda has been this neglected arena of endeavor. If you look at what we have, it’s almost embarrassing. Diagnostics that are decades, decades, decades old. A vaccine that doesn’t work for adult pulmonary TB. Treatment regimens that have not been rejuvenated for the last several decades. We don’t even understand the fundamentals of host-pathogen interaction. These are questions that should have been asked, but weren’t, because we were so successful in the developed world, of addressing TB.

I use the AIDS comparison. We poured a lot of resources into it, and got a lot of good young people involved in it. We now, really, have an extraordinary handle on the pathogenesis, the pathophysiology, the targets for drug development. Those are the things we need to do with TB. We’ve got to get young investigators to realize there are enormous and exciting opportunities, not only for their own careers, but because they are dealing with a disease of extraordinary relevance.

X: Do you run into a certain amount of scientific snobbery? You mentioned an anecdote of a scientist in your talk who told you that TB is something we’ve already figured out, haven’t we?

AF: I wouldn’t call it scientific snobbery, but I’d call it a lack of appreciation for the opportunities involved with TB research. That’s the reason I carefully chose my introductory paragraphs in that talk. I know people will say we already have in our grasp what we need to control TB. All we need to do is implement that. You need to look at TB in the broader context of global health in general. And of infectious diseases in general. Because what you learn about host-pathogen interactions for TB, although it’s specific for TB, it’s applicable to many other infectious diseases. So when you encourage young people to get involved with TB research, you’re not just talking about one microbe, you’re talking about a whole constellation of host-pathogen interactions that will have relevance well beyond TB.

X: You talked about instead of thinking incrementally, for scientists to think transformationally about TB. How would you define success five or 10 years down the road?

AF: I’d define success as having a self-sustaining research endeavor, with spinoffs that go well beyond TB. That’s success. Probing host-pathogen interactions. Understanding what the nature of TB latency is [in which the infection lies dormant]. We need to know what the spectrum of latency is.

You really need something concrete. You need a state-of-the-art, point-of-care molecular diagnostic tool. You need new drugs and drug regimens. You need a vaccine that works against pulmonary TB. You also need a sustainable research community in TB that will not let it go again into the valley.

X: Could this follow the HIV model, in which you start out with a less-than-optimal paradigm of people taking a whole bunch of pills per day, but the regimens get simplified or combined over time?

AF: Absolutely. That’s what I mean by saying let’s not be incremental, let’s be transformative. We need to understand what the nature of resistance is. What the nature of latency is. Should we be treating certain people who have latent infection? If so, which ones? Everything is on the table.

X: What would you say are the top two or three rate-limiting factors against progress now?

AF: One of the rate-limiting factors is the number of qualified investigators entering the field, and the other is that we’re dealing in an era of limited research resources. That doesn’t mean we throw up our hands and give up. We just push harder and harder.

X: Didn’t you also mention the clinical trial network, and how there’s a shortage of available facilities for clinical testing of new TB drugs?

AF: Yes. There’s no problem there. I’m going to try to utilize the network we have to incorporate questions that are relevant to TB, more than we have been. I haven’t made that decision yet. I’m calling on a group of advisors to see what the feasibility of that is. We already have a very well-funded, extensive, clinical trial network. Can we incorporate clinical trials related to TB into that network? I don’t know the answer to that, but I’m going to explore that.

X: What can the biotech and pharmaceutical industry do to be a better partner? Or do you see them simply following along after the basic research priorities get set by NIH?

AF: They don’t. We contribute to their capabilities in what they can pursue, by making fundamental basic observations. The biotech companies and pharma are eminently more qualified than the basic research community in taking that concept and developing it into a product. I see it as a continuum of the basic research that we fund, and the development of a countermeasure like a diagnostic, a therapeutic, a vaccine. It’s an important part of the continuum.

X: But this wasn’t a big priority of the U.S. government in the 1980s. It’s becoming a little bit more so, but it’s still certainly not a front-burner priority in pharma either, right?

AF: If you go into those sessions and listen to people from biotech and pharma, you can see they’re starting to get interested in it. They certainly are. We are starting to see some change.

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2 responses to “HIV’s “Tireless Warrior,” Anthony Fauci, Calls for Transformation of TB Research”

  1. Peter Small says:

    There has been a tremendous amount of innovation for TB after 40 years of nearly no progress. Today we have a pipeline of 9 drug candidates and 5 vaccines. People in BRICS countries, and across the developing world are taking ownership and contributing to this innovation. There is always more to be done – more new ideas, more collaboration, more money — but today we have great optimism about where the field is heading.

  2. King Holmes says:

    Tony’s call to action was very timely and was a highlight of the Summit, which aims to achieve transformational strengthening of the global response to TB.

    I also expressed the need to improve health systems, and the global commitment to more effective use of the tools we do have available today to prevent TB. Specifically, we need to strengthen not only more effective treatment of clinically active cases of active TB, but also implementation of intensive TB case findings and isoniazide prophylactic therapies in populations who are particularly vunerable to TB, e.g., those with HIV infection and those recently exposed to active TB.

    For example, we can more effectively use Community Health Workers for close follow-up of those on isoniazide preventive therapy; we can prevent transmission of TB in clinical, hospital, prison settings, and other places where people congregate.

    In conclusion, we need more effective tools, including diagnostic tests, new drugs for treatment and eventually vaccines for TB, but meanwhile we need to make more effective use of the tools we have.

    King Holmes
    William H. Foege Chair, Director, Center for AIDS and STD, Global Health
    Harborview Medical Center