quarta-feira, 2 de março de 2011

Kary Mullis e suas "silver bullets"

Kary Mullis foi laureado com o Prêmio Nobel em Química (1993) por ter desenvolvido a revolucionária técnica de PCR. Em entrevista publicada hoje na Seed Magazine, Mullis conta sobre suas estratégias para "curar" as mais diversas doenças infecciosas. Link para o texto original está aqui.


Kary Mullis, a self-proclaimed non-specialist, won the Nobel Prize for developing the polymerase chain reaction (PCR), a technique that allows researchers to quickly and cheaply make many copies of single strands of DNA. For the past decade Mullis has been using PCR to create new types of drugs that could soon provide a cure for everything from malaria to anthrax. He tells Seed how he is bridging the gap between disparate scientific fields to devise a radical new way to combat infectious diseases.

Seed: Why do we need to rethink the way we treat infectious diseases?
Kary Mullis: Many pathogens are becoming resistant to our antibiotics. Consider penicillin, for example. We took it from a fungus that grew in the soil and killed bacteria for food. Because of this warfare, some bacteria had developed a resistance via DNA, to penicillin. Over time, they passed this resistance via DNA up to the pathogens that infect our bodies. So now many organisms—like Staphylococcus aureu, the cause of Staph infections—are, in large part, unaffected by penicillin. In this way a lot of bacteria have mutated around our antibiotics.

The standard pharmaceutical response is to go stomping through the jungle trying to find extracts of all the organisms and see if one of them will inhibit the growth of particular bacteria. And that of course will get more and more difficult as time goes on. It is clear that we need another solution.

Seed: What is your solution?
KM: A long time ago they used to speculate that there might be what they called a “silver bullet” for cancer. The idea was that if you could find some molecule that would bind to a cancerous cell but not to a non-cancerous cell and attach a radioactive atom—or some sort of poison—to that molecule, you could cure cancer. It turned out cancer didn’t work that way, but you can take a similar approach to fighting infectious diseases.

My work with PCR allowed for the invention by Craig Tuerk of nucleic aptamers, which are tiny binding molecules that can be designed to attach themselves to harmful bacteria. However, instead of attaching a poison to the other end of the aptamer—as the silver-bullet strategy would call for—I put something on there that is a target for our immune system, a chemical compound with which the immune system is already familiar and to which it is very strongly immune. What you end up with is a drug that will drag this thing to which you are highly immune over to some bacteria you don’t want in your body. And your immune system will attack and kill it.

Seed: Do you have any proof that it works?
KM: Yes, we cured anthrax in mice. If you infect a mouse with anthrax and then wait 24 hours and treat it with a penicillin-type drug, you get about a 40 percent survival rate. But using our drug you get a 100 percent survival rate. Of course, it is unlikely that you are going to get anthrax, but that is sort of a model system.

Seed: It sounds like, at least in theory, the method you have developed could be used to cure any infectious disease.
KM: That’s right. In fact, the science part of it, as far as I’m concerned, is pretty much taken care of. For any particular disease you need a bunch of people to help you because you need organic chemists and infectious disease specialists, but there really aren’t any serious hurdles. A whole lot of people just have to apply the methodology we developed.

Of course, we will need to get through to the big drug companies that can set up human trials and ultimately manufacture the drugs. My reputation will at least get me into their office—though if I make a fool of myself I won’t get to come back.

Seed: Do you think a lot of ideas like yours go overlooked simply because those who have them don’t have your reputation?
KM: Yes, I think supporting early ideas is a really neglected area of science. Where is the foundation that rewards very early ideas that don’t yet have a lab or a company behind them? There are lots of these ideas out there, but nowhere to send them.

What we should be asking about a brand new idea is, “Does it have a chance of ever working?” And if the answer is “yes,” we should consider supporting it. We don’t need to give it a million dollars, just enough money to prove itself. Because today, by the time you get most science prizes, you already have 200 people working on an idea. That’s not when the idea is delicate.

Seed: You have said that you are not a specialist. The non-specialist is an increasingly rare breed in science. What do 
you understand your role to be in today’s highly specialized scientific research community?
KM: I am undisciplined—a loose cannon on deck is one way to talk about me. The positive spin you can put on it is that I can say to one specialist, “You have got some knowledge that, put together with this guy who is an organic chemist and with this guy who knows about influenza in chickens, can accomplish something that none of us could do on our own.” That sounds corny, but it takes years to make those kinds of connections—and doing so requires people wide open with their interests.

It takes a while for me to find people who really understand what I am trying to do and are willing to play in my arena. That is a valuable thing. To be able to collaborate with people is essential, because we can’t do all the things that we can 
think about.

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