An Expanded Biodefense Role for the
National Institutes of Health

A Generic Approach

Dr. Fauci said that to defend against bioterrorism, the Institute is focusing on major threats, classed as category “A” agents—smallpox, anthrax, tularemia, plague, botulism toxin, and hemorrhagic fever viruses, but also looking at category “B” and “C” agents, such as foodborne E. coli and staphylococcus. “We’re dealing with bioterrorism and not biowarfare,” he said, so “there are really many agents” that could be disruptive.

The job is a complex one, and Dr. Fauci doesn’t think it’s fully appreciated.

“What we’re planning to do is going to be generic to virtually all” microbes that might be used in bioterrorism, he said. The work requires understanding of “fundamental microbial physiology” and “sequencing of virtually any potential pathogens” to identify “targets for diagnostics, therapeutics and vaccines,” but the work also requires researchers to “look at host immune response to microbes.”

“So not only are you looking at microbial physiology, but you’re looking at the physiology of the human host. What can we do to boost the immune system against agents for which we have no vaccine? What is the relationship between the innate immune system and the adaptive immune system?” The innate immune system, he explained, is “the initial primitive response” to any microbe. “All of these things are going to be studied in depth in a comprehensive look at bioterrorism,” he said.

The NIAID, he said, is “going to put a significant amount of resources” into “physical facilities to study any microbe—select agents as well as agents that are not on the select agent list—in addition to training a new cadre of investigators in infectious diseases and host defense mechanisms,” knowledge that will be used in defending against bioterrorism agents. “You build up both the physical and manpower infrastructure to be able to do biodefense or counter-bioterrorism research. That’s really very much ingrained in our strategic plan and our research agenda.”

Working to defend against bioterrorism, he noted, will not take away from research in other areas. First, the bioterrorism money that the NIH is getting is “all new, and not being moved from another program.” Second, “If done properly, the kind of generic research we do will ultimately benefit” research “outside the field of bioterrorism”—for example, treatment for hepatitis C. “You have an antiviral program. It isn’t just directed at one microbe, but rather looks at all of the potential targets in different classes of viruses.

“So I fully expect that when we develop antivirals against diseases like Lhasa and Ebola, Marburg, and smallpox, we’re going to fall upon antivirals for hepatitis C.” A classic example, said Dr. Fauci, is lamivudine, or 3TC, a drug developed to fight HIV. “It is now the best drug against hepatitis B. We developed another antiviral” for use against HIV and “now use it against lamivudine-resistant hepatitis B.” Another drug that was used to treat cytomegalovirus complications in people with advanced HIV disease turned out to be “highly active against pox viruses, and that class of drugs is going to serve as the prototype for developing antivirals against smallpox.”

“Our goal within the next 20 years is ‘bug to drug’ in 24 hours,” he said. “This would specifically meet the challenge of genetically engineered bioagents.” Within a day’s time a treatment could be identified—the bioagent would be matched to a drug to combat it. Someone might genetically engineer a microbe and make it resistant to the standard treatment, but if that trait is identified, “you don’t have to create another drug.” For example, if anthrax were made resistant to ciproflaxacin, “we probably would have used clindamycin.”

This method would not be effective, however, against an entirely new disease. “It would be virtually impossible to create a new drug from scratch in 24 hours,” said Dr. Fauci.

One solution to the threat is “pre-clinical detection”—diagnostics before infection takes place. The Institute is investigating pre-clinical detection, but Dr. Fauci wouldn’t speculate as to when it might become a reality. He said, however, that it is “absolutely” worth spending the money on.

The Need to Educate the Public

Dr. Fauci thinks that bioterrorism is “just a new concept to people.… There are so many complicated issues. An example is smallpox. People say, ‘Why don’t you just vaccinate everybody against smallpox?’” He said that the issue is complex, but that it involves the sheer amount of vaccine needed for everyone, and that there is now nearly enough vaccine to vaccinate everybody. One question he is facing is “How much is enough?” The vaccine can be diluted and still be effective. It has been tested at a ratio of 10 to 1, and it works. “But we probably won’t go greater than” 5 to 1, “because you want to leave a cushion,” said Dr. Fauci. Aventis Pasteur, he said, is going to provide 75 million doses of their smallpox vaccine to the federal government for a nominal amount. Under a contract with Acambis Inc., with support from its subcontractor Baxter International Inc., enough doses of another smallpox vaccine will be manufactured for everyone by the end of 2002.

Once there is enough smallpox vaccine for the United States, additional vaccine might be needed to combat an outbreak in Asia or Central Europe, for example. Although other countries—Dr. Fauci mentioned France—are starting to produce smallpox vaccine, he stated that “we would have some responsibility to try and contain an epidemic elsewhere, because if it’s elsewhere, sooner or later it’s going to come here.”

However, even once there is enough vaccine, he doesn’t necessarily want to vaccinate everybody in the United States. The public, Dr. Fauci stated, needs to understand “the pros and the cons of preemptive versus reactive vaccination.… What I’m going to recommend is that we have some sort of an open public forum or dialogue, like a town meeting.”

Educating the public, he said, is “a long, drawn-out, difficult process.” It’s not enough to “get on the nightly news once and say, ‘By the way, we’ve got a problem here.’” It has to be done constantly with public-service announcements, programs, town hall meetings, literature, and newspapers. “It’s going to be a sustained effort.” Dr. Fauci cited his experience in educating the public about HIV and AIDS.

We really have to make the public aware of relative risk, real risk, and perceived risk, he said. When risks aren’t controllable, he stated, people want zero risk. Letters containing anthrax, he said, are out of the recipient’s control: they may arrive anonymously and without warning. As individuals, we can’t personally prevent the letters from being sent, so we want the risk eliminated. “But when we have control over risk, we don’t mind risk.” The chance of receiving an anthrax letter is remote. “There’s a better chance of my getting killed by somebody running a red light,” he pointed out. But people feel that they can control that kind of risk by driving defensively. “We need to cultivate that type of thinking on the part of the American people,” he said. “We’re going to have to live with risks.” If we recognize the risk and defend against it, then the response to episodes of bioterrorism “will be much more controlled and controllable.”

Dr. Fauci also mentioned the AIDS crisis in the context of recruiting researchers. “We certainly need to train additional scientists to fulfill the upcoming needs in the area of research on biodefense,” he said. “We have done a good job in training infectious diseases experts in general. However, there needs to be an accelerated and sustained effort to draw more competent scientists/researchers into the field of research on counter-bioterrorism. Historically, we succeeded over time in drawing people to the field of HIV/AIDS research despite the fact that at the beginning of the epidemic, very few researchers were interested in the area. Now we have a robust cohort of AIDS investigators.”

Coordination With the U.S. Army Medical Research Institute of Infectious Diseases

In working to defend against bioterrorism, the NIH will benefit from its relationship with the Army. “We at the NIAID have always had good interaction, collaboration, and cooperation with” the U.S. Army Medical Research Institute of Infectious Diseases, said Dr. Fauci. “The Army has two types of infectious diseases programs. They have their standard infectious diseases command, and they have now the biodefense command.” The researchers studying infectious diseases are concerned about problems such as cholera, HIV, gonorrhea, syphilis, malaria—all the things that might be a threat to the troops. In those areas the NIH and the Army have “had phenomenal collaboration.”

What they haven’t had, because of the classified nature of the research, is much open interaction with the biodefense command, but that is starting to change. Dr. Fauci expects that in the next few years, the NIH will be doing a lot of work in partnership with the Department of Defense.

The Public Health System

Another area in which the NIH depends on other government organizations to defend against bioterrorism is the public health system. “In general we have a good public health system for certain things,” said Dr. Fauci. “What we don’t have is something that we really lost … a very strong local and state public health system.” It was needed during the days when there was a lot of tuberculosis, measles, and smallpox. We no longer have that local public health infrastructure. Over the decades, it “has gone into some disrepair and disarray, and that’s what needs to be built up, and that’s why a significant portion of the counter-bioterrorism funds that are being put forth by the Administration and Congress” are “directed at enhancing the local public health infrastructure.” Health care availability, he said, is great. “But when it comes to bioterrorism and its insidious infectious diseases, we’ve let slip something that was once pretty good. Now we need it to be good again.”

Research and Responsibility

At times, said Dr. Fauci, the medical community must be prepared to admit that it doesn’t know or have the answer, and that saying otherwise can lead to even more problems. “The medical community and the public health officials need to be able to say, ‘I don’t know,’ at the same time that they say what they do know,” and to give the calculated level of risk, he said. “If you act like you do know and something [unexpected] happens, then you lose all of your credibility.”

This represents another area in which the American public and all the world’s public need to be educated, said Dr. Fauci. They generally think of science as an absolute thing. Science tells us that “if you smoke, there is a good chance you’ll get cancer. If you have a cholesterol count of 800, the chances are you will have a heart attack. So when the general public think of science, they think of absolutes,” as if there were a mathematical formula. “What they don’t experience, or are not privy to, is the completely iterative nature of science.” Science, he said, consists of “starts and stops, until you get the right answer.” When there isn’t an absolute answer, the scientific community and the public health community still “want to give to the public what they demand.” The public needs to realize that science may not be able to you the answer right away, he said.

Although Dr. Fauci thinks there needs to be a review of the way information is exchanged, he would like scientific research to be more transparent—that is, openly disseminated, even though it entails risk: if we publish our breakthroughs in open sources, might this drive our enemies into attacking different targets? “A segment of our intelligence people … feel that announcing the availability of a response” will lead our enemies to create an improved version—if we make an antiviral drug against Ebola, then someone will make a strain of Ebola that’s resistant to it. “It is more likely that if we make a good drug against Ebola,” whoever has Ebola will say, “Well, forget Ebola. They’ve got a good antiviral against it.” Dr. Fauci says that by announcing that we have a therapy, we eliminate it as a threat and that with the pressure on countries that are trying to make weapons of mass destruction, it is going to be harder for our enemies to make something like drug-resistant Ebola.

There’s another result of publishing information on a good antibiotic, says Dr. Fauci: somebody will want to make a better one. For everyone who responds by trying to make a stronger bioweapon, “there are twenty scientists who are out making even better antivirals. That’s the way the field is, it’s a competitive field.”

However, “when people get into certain lines of research, we need to be circumspect,” he said; however, he emphasized the difference among “restricting research, restricting reporting, and letting anybody do anything they want to do.” We’re much more aware, he said, that things might be used in a way that is harmful or deleterious. But he pointed out it would not be “the government deciding strictly what can be done.… we need to create a culture of responsibility among the researchers.”