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24-10-2016Academy Laureates
24-10-2016Kavli Submit
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You've worked on a project developing molecules that inhibit the anthrax lethal factor - a component of anthrax toxin.  What can you tell us about that?
The general idea is identifying specific drugs which can inhibit the activity of these toxins - the anthrax lethal factor and the anthrax edema factor - inside cells.  The problem is that the symptoms of the disease become evident too late, when the infection is too advanced to be controlled only by antibiotics.  By finding specific drugs against these two toxins, you would help in finding efficacious therapeutic protocols.

So those inhibitors could be used in conjunction with antibiotics?
Not alone, because these bacteria proliferate very rapidly in the lymphatic system and the blood.  As the pathology is due both to the bacteria themselves and the toxins, you have to attack both targets.

Your research has also led to investigations of snake toxins.  What kinds of snakes are involved and how do their toxins work?
Snake bites (snake envenomation) is a forgotten disease, because we are interested mostly in what is important for the more developed countries.  But snakes kill many people around the world, particularly in South America and Southeast Asia.  I was attracted by the pathology caused by [the venom of] some of these snakes, which is actually similar to that of botulism.  We found out that the snake presynaptic neurotoxins cause a neuromuscular paralysis similar to that caused by the botulinum neurotoxin, but with a different mechanism.  These snakes were from Southeast Asia (Bungarus) and from Australia - the tiger snake and the brown snake.  A major component of their venom are neurotoxins which practically destroy the nerve terminal, and yet in the mouse, within two to three weeks, the neuromuscular junction reforms exactly as it was before - a total recovery of function.  These patients, if you help the respiration mechanically, they recover completely, as do patients with botulism.  It's a form of synaptic plasticity which is very interesting to study.

Do you think snake toxins could ever be applied as a therapeutic?
We're working on that.  I think we're moving in the right direction, particularly for the treatment of hypersweating.

Do you ever work with the snakes themselves?
I'm coming from a stage where I spent three months in Costa Rica, where I studied myotoxins.  I had to handle the snakes, but if you take some precautions, it's not that difficult.  These snakes are impressive, particularly when you see them in the wild.  You hardly can discern them; they are so mimetic that you can't see them.

What do you think is the most understudied microbial system?
I think we should pay much more attention to the intestinal flora, because by studying the intestinal flora and mucosal immunology, we could really understand much more about the interplay between the pathogen and the host.  And now we have techniques, particularly in genomics and new methods of cultivation that would allow us to attack this problem.

What is your favorite microbe?  Why?
My favorite microbes are definitely the clostridia which produce tetanus and botulinum neurotoxins because they occupy a very particular, specific niche of the body, and they are present in the entire world in the form of spores (so they cycle between spores and vegetative form).  Minute amounts of tetanus toxin produced in the tip of the toe can migrate inside the nerve, reach the central nervous system, and intoxicate the nervous system.  This is incredible to me.

If you could name a new microbe right now, would you name it after yourself?  If not, how would you name it?
I would name it for the place where it was found or for the university where it was studied.  Modern science is no longer all about the individual; it's more a population effort.  If I found a new bacterium, I would like to acknowledge this modern aspect of science by naming it after a place rather than after an individual.

What advice would you give students about life as a microbiologist working in academia? Academia (at least in Europe) provides a place where one can develop long-term studies; one can develop the study of forgotten diseases.  One can really still answer fundamental questions.  As a microbiologist in academia, one can develop long term projects and try to do, for example, isolation of new bacteria or address very difficult problems that require a prolonged effort.  Still, it's changing here; there is not the freedom that I had in the beginning of my career.