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Kary Mullis - 2

Redirecting the Immune System:
An Interview with Dr. Kary Mullis

By David Jay Brown

Kary Mullis, Ph.D., won the 1993 Nobel Prize in Chemistry for his invention of the polymerase chain reaction (PCR), which revolutionized the study of genetics. The journal Science listed Dr. Mullis’ invention of PCR as one of the most important scientific breakthroughs in human history.

PCR is a technique that allows chemists to easily, and inexpensively, replicate as much precise DNA as they need. This solved a core problem in genetics. Before PCR, the existing methods for making copies of those particular strands of DNA that one was interested in were slow, expensive and imprecise. The brilliance behind this invention, as well as it utter simplicity, lies in PCR’s ability to turn the job over to the very biomolecules that nature uses for copying DNA. PCR multiplies a single, microscopic strand of genetic material billions of times within hours. The process has many applications in medicine, genetics, biotechnology and forensics.

When the Royal Swedish Academy of Sciences awarded Dr. Mullis the Nobel Prize, they said it had “hastened the rapid development of genetic engineering” and “greatly stimulated biochemical research and opened the way for new applications in medicine and biology.” Just flipping through any current issue of the journals Science or Nature one will encounter advertisements for PCR systems every few pages. In addition to revolutionizing the study of genetics, it’s also influenced popular culture and science fiction. Because PCR has the ability to extract DNA from fossils, it was the theoretical basis for the motion picture Jurassic Park. In reality, PCR is the basis of an entirely new scientific discipline, paleobiology.

Dr. Mullis earned his Ph.D. degree in biochemistry from the University of California at Berkeley in 1972. He has authored several major patents, and has received numerous, highly prestigious awards-including the Japan Prize in 1993, the Thomas A. Edison Award (1993), and the California Scientist of the Year Award (1992). He was inducted into the National Inventors Hall of Fame in 1998.

Dr. Mullis is the author of the book Dancing Naked In the Mind Field, an autobiographical account of his fascinating, and sometimes mind-bending adventures, which makes a compelling case for the existence of greater mystery in the world around us.

Dr. Mullis is currently a Distinguished Researcher at Children’s Hospital Oakland Research Institute. He also serves on the board of scientific advisors of several companies, provides expert advice in legal matters involving DNA, and is a frequent lecturer at college campuses, corporations and academic meetings around the world. He is the inventor and founder of Altermune LLC. To find out more about Dr. Mullis’ work, visit his Web site: www.karymullis.com

In the following interview Kary and I discussed his current research, which offers tremendous hope as a medical treatment for dealing with virtually any type of pathogen by engaging the immune system in a novel way. 

David: Can you tell me about your latest research project?

Kary: I’m in the process of starting a project which involves a way to redirect the immune system from one target to another, by using a chemical linker that will link an immune response that you have made for one thing to a new target, a target to which you would now like to be immune.

David: How far along are you with this project?

Kary: We already know how to do it, and the experiments that we’ve tried to do it in with baby rats have worked. In the experiments we were able to take an immune response in baby rats that was made for this irrelevant organic chemical called phenylarsonic acid, and redirect that to this bacterium that would normally kill rats in a couple of days. By using this method we made it so that the bacterium wasn’t able to grow in them at all. The bacterium that we injected in them, Haemophilus influenzae, would have killed them within two days. We gave them the organism first. Then, right after that, we gave them the thing that was going to protect them, and it worked in a really big way. The untreated rats that got the Haemophilus influenzae had something like a million microorganisms per milliliter of their blood in 24 hours. It grows really fast in a baby rat. The ones that got our treatment had none that were detectable which in our protocol is less than 20 per milliliter. So it was a big deal.

That experiment was a contrived experiment. We didn’t start with a human that had been accidentally exposed to some pathogen. We started with some rats that had been intentionally exposed, and we knew exactly when and how much. We think that we can take that same system and adapt it, not only to humans, but to just about any human pathogen that we can define beforehand.

For instance, people have defined the pathogen that causes anthrax. We can isolate and grow it in the lab. We can make something that will bind to it. In fact, there are lots of people who have already made things that combine with anthrax. What this invention does is take the thing that combines with anthrax, and uses it as one end of a linker, the other end of which binds to the immune response that we already have. The invention is called Altermune, and it defines a class of drugs. In the case of the rats, we injected it in them. Hopefully, we’re going to be able to produce Altermune type drugs that you could ingest, so you won’t even have to have them injected. But if you’ve just been infected with smallpox, you won’t mind an injection.

David: What are some of the other potential applications that you see for it?

Kary: Most of the possibilities that immediately come to mind have to do with infectious disease. The way we’ve dealt with modifying our immune system since 1794-when Jenner discovered vaccination-hasn’t changed. We vaccinate ourselves for all kinds of things, and we do it in that way-by giving ourselves a damaged or dead copy of what we would like to be immune to. We inject it into your body, and you make an immune response to it over a period of a few weeks or months. Sometimes we have to give it to you on several occasions during that time. You make a whole bunch of antibodies, some of which will bind directly to that thing that we stuck in you or anything like it, and it permanently affects your immune system.

You can make someone immune to anthrax by vaccination, but if it has negative side-effects, they’re permanent. The Altermune method takes an immune response that you already have, and, temporarily redirects it to some target to which you now want to be immune. For the method to work, you have to be prepared for it by having the pathogen in hand, in a fairly purified form. For most of the organisms that we’re worried about in terms of bioterrorism, we do.

That’s what causes the worry about them-people have been working on them, and they’re around. Things like cholera or smallpox, all kinds of terrible things that people have been plagued by, and most of the people in the civilized world are no longer immune to them.

David: The implications sound staggering. What about diseases like cancer and AIDS?

Kary: Everybody asks, what about cancer?  Cancer is not at all like an infectious disease, in the sense that every cancer cell is not like every other cancer cell, even in the same tumor. Cancer is a tough one. First I’m going to deal with diseases that we know the exact nature of, where an organism is responsible for it, and the absence of that organism will cure it. That’s most infectious diseases.

AIDS doesn’t fall into that category. Nor does it affect many people despite the press that it gets.  Plus, the AIDS scientists say you can cure HIV if you want to, but you still don’t cure AIDS, because the disease has already done something to you. In terms of an infectious disease it’s kind of an oddball thing. I don’t think most of the research is reliable and I am not willing to spend a lot of effort on it. I’m one of the few outspoken people who say that there’s no good scientific evidence that the diseases that are called AIDS are really caused by the retrovirus called HIV-in spite of its name. I’ve had a lot of trouble from people over that issue, because many are convinced that it does. But my assessment is that it is an unsupported and unsubstantiated belief.

There are all kinds of possibilities for the first Altermune targets, but we’re going to concentrate on potential bioweapons. There’s a list of about twenty different pathogens that people have associated with various biological warfare programs. Most of them came from the Soviet Union, but some of them were developed in the US before 1969, when we stopped making them.

There’s fear that some of the pathogens have been produced intentionally and are still out there. How long is it going to be before somebody gives himself smallpox, flies to New York, and walks around for a couple of weeks until he dies? How many people would he infect? How many people would they infect? We have vaccines that may or may not be protective-nobody knows for sure. They might not work fast enough. They’re slow in terms of producing their results. With Altermune drugs, you don’t have to grow a new immune

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