Sometime in the 1970s, medical science and many governments around the world grew complacent about infectious diseases. Antibiotics reigned supreme. Our most ancient enemies seemed to have just gone away. Well, they’re back, and 125 new drugs and vaccines have been rushed into development, a 33 percent increase in just a few years. Dr. Alan Proctor, who directs cancer, immunology and infectious disease research for the pharmaceutical giant, Pfizer Inc., sheds some light on a major public health problem.
Q: Why have disease-causing organisms grown resistant to the drugs designed to kill them?
A: I think we underestimated their ability to adapt. If you look around the world, malaria is resurging. Tuberculosis has returned.
Q: How do you document drug-resistance in this country?
A: We get regional outbreaks, as we had in Tennessee a couple years ago, where more than 40 percent of the children with respiratory infections, inner-ear infections and infected sinuses were not responding to treatment.
Q: Bacteria are self-contained, single-celled organisms. What makes them vulnerable to antibiotics?
A: They kill bacteria in different ways. The penicillin-type molecule interferes with the formation of the bacterial cell wall. The bug continues to grow, but it’s weakened structurally and eventually explodes.
Other antibiotics interfere with how the bacteria make the proteins they need to survive. Or a drug may try to block DNA replication–the way bacterial cells copy their genes. So antibiotics will attack bacteria on several fronts, and just as busily the bacteria have been learning how to defend themselves.
Q: How do they do it?
A: They somehow destroy the antibiotics. Or they change parts of their own cells that the drug interacts with. Or they even may develop tiny pumps that kick the drug out of the cell as fast as it goes in.
Unfortunately, we’re also seeing bacteria become resistant to the same antibiotic in multiple ways. A decade ago, we could try to figure out ways to enable the old drugs to still work. But as a strategy for the future, that’s no winner.
Q: What have you decided to do?
A: Our strategy in the industry is to sidestep the patterns of resistance that are showing up. We want to develop new classes of antibacterial agents that the organisms have not had the opportunity to evolve defenses against.
It will take powerful new medicines. We’re turning our attention away from modifying existing classes of drugs and shooting for major breakthroughs. We need new miracle drugs, like we had with penicillin in 1939.
Q: How long will it take the microbes to catch on?
A: Hard to say. I’m afraid we’ll be dealing with the problem forever. It’s like trying to stop evolution.
Q: Your industry spends $2 billion a year for research against infectious diseases. That sounds like a lot, until one realizes that $14 billion is going toward other diseases. What’s going on?
A: I suppose that everyone wants to cure cancer, heart disease, diabetes. But there’s a lot of stuff in the infectious disease pipeline. Not long ago, very few new medicines were being developed for viruses and fungal infections. Now, there are 25 antivirals and 14 antifungals in various stages.
Q: In terms of public health strategies, vaccines that prevent diseases are always a better idea than drugs to treat someone who gets sick. What is the vaccine picture?
A: As recently as 1994, about 12 infectious disease vaccines were being tested; now 38 are in development. They include new vaccines against Lyme disease, herpes, influenza, chickenpox, typhoid, diarrhea and gastroenteritis.
Q: Why is diarrhea such a big problem?
A: Diarrheal diseases are a major cause of death globally–more than 400 million cases of campylobacter diarrhea occur each year, with 2.6 million in the United States alone.
Q; What about new antibiotics?
A: Twenty-seven antibiotics are being developed, including drugs for respiratory infections, sepsis and sinus infections.
Q: Your industry seems especially worried about the emergence of drug-resistant organisms in hospitals.
A: Yes. We’re finding new versions of microbes in surgical and intensive care units for which there are no drugs available. People are dying of those infections, though fortunately they are rare.
Q: Is there too much optimism today about protease inhibitors, the new AIDS drugs?
A: The viral loads go down quickly, even below detection in some patients, and that means the immune cells are rebounding.
But this is no cure. And there are going to be problems with resistance to these drugs.
Q: Yet a proof of principle has been established?
A: Definitely. If we keep up the effort, we’re going to be able to treat this disease. The problem is that some of the cells HIV integrates with may be in difficult places, like the brain, where cells live for years instead of days, as in the immune system.
Q: So, there’s little chance of actually ridding the body of all the virus?
A: I think the chances of that happening are very slim.
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An edited transcript
