Wednesday, July 02, 2014

Ferrets are not humans


Poster 1: Outbreak.
    There is a great deal of controversy in science. But the important problem lies here. People who know the actual science don't talk about it as much as the pseudo science people boast about the non science. This creates a gap, where common people don't understand the complexity of science and the methods to conduct science. So, when there is a talk about a new BSL-4 Laboratory around the town, gain of function research, a concept called as "DURC" pops into the headlines and people are scared the hell out of them. I must acknowledge that some excellent science programmes like the one hosted by Vincent and his team (Link), Radiolab, TED talks and many more, which brings the science to layman language level. However not everyone reads journals and listen to authentic science. Movies like contagion and outbreak have led to assumption in people that someday a lab is going to create a strain that destroys the humanity.. Crap. They are movies, not realities. There is a difference.

   So what does DURC actually mean? DURC stands for Dual Use Research of Concern. The whole concept dates pack to the influenza paper on gain of function experiments (See my previous blog posts here and here). And when some irresponsible reporter posted "Ferret died in experiment", people were not communicated properly by the scientists. Instead opinions were voiced in standard journals which common people never read anyway. Results, too much confusion. And finally the paper was published, showing not a ferret died. Moreover, ferrets are not humans. They are study models. To date, I have never heard of some bio terrorism act using the details in paper. Actually, in practice you can never do it in nature with success.

     Gain of function research, is a controversial hot topic of the day. Media equates the concept with ability to kill. The point is it is not. Let me explain. Let us consider a hypothetical bacteria which causes a particular infection. For understanding molecular mechanisms of how the bacteria works inside the host, scientist in a lab will study the bacteria in a cellular model and (or) animal model. In a normal routine inside the laboratory, genome of the bacteria is played around with, by changing some genes and looking at how it effects the overall outcome of infectious process. That is how virulence is studied. There are well established protocols for these studies, and are done in strict containment facilities. Now let us assume that during generation of the mutant types, a bacteria strain emerged that gained a new function, say more potent toxin than the original it had. In other words, the bacteria has gained a function. But does that pose a threat? The answer is "very unlikely". It is just not potency of virulence that matters in a organism. There is a second, but more important factor called as "Fitness factor".

     You could track a zillion research paper on fitness cost of having a new gene around. For example, MRSA has a additional gene to resist the Methicillin class of antibiotics. But then they also have a reduced fitness of survival. However, in an environment where the organism is constantly exposed to Methicillin, despite the reduced fitness, it helps in survival. Hence the gene is still there. If the MRSA is mixed with a MSSA without the pressure of antibiotics, chances are more that MRSA will vanish from the pool. In other words, MRSA is best adapted to the antibiotic condition. Now let us apply the same logic, to what would happen if there is a gain of function say in influenza. Probabilities are that the influenza is lab adapted. In the outside world, it just wouldn't survive. You may ask, what if by any chance that the gain of function, has lead to both increase in fitness and function? Well, if there is ever such a chance, nature would have already created it, even before you have thought about it. That is the concept of evolution. See my previous posts here and here

      Of course, I by no means say that we should let scientists do anything that they want. That is why there are ethical boards in institutes (Called as IRB, Institutional review Board) which scrutinizes the research and ensures that these work are carried out in strict ethical and standard conditions. Biosafety is a norm of standard research practice. Based on the potential of an organism, in terms of human health, there are different biosafety levels each with stringer conditions for harder pathogens. The highest possible containment system is a BSL-4 Laboratory.

     There is a recent case of resistance against the opening of BSL-4, Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) laboratory. The laboratory had taken all steps to ensure containment and have passed all the quality checks. However the concern was so high that the matter ended up in court. Recently, the court declared that the facility is ready to go (Link). Here's a funny point. The people who resisted (or lets say protested) doesn't know how a BSL-4 operates. Nor did they care to learn. There is a hour long video that demonstrates everything you need to know about the working of these laboratory. See the YouTube video Threading the NEIDL, Link. I strongly recommend that you watch it.

     A paper was published recently, claiming that laboratories represent a area of potential pandemic (Link). I have no clue why an opinion in biological safety is published in a magazine of Atomic science. Anyway, TWiV 287 (Link), has a very detailed discussion of how the paper is totally flawed and doesn't represent anything scientific. I cannot agree better.

       And now there is a new controversy, just published in Nature news that inspired me to write this page. The study in question is led by Kawaoka, to investigate what made the 1918 H1N1 virus hyper virulent. As per the report, there is an apparent disagreement between University of Wisconsin–Madison and US National Institute of Allergy and Infectious Diseases (NIAID). I have Quoted the article below (in blue, with my comments inserted in red).

The team used genes from wild avian H1N1 viruses that coded for proteins resembling those of the 1918 virus to construct new viruses (Gain of function experiment). The new viruses were not only able to spread between ferrets — the best current model (It is a model. Ferrets are not humans) for human flu transmission — they were also more virulent than the original avian viruses. The team therefore argues that there is a high risk that a 1918-like virus could emerge naturally (And what crap conclusion is that??)

Photo 1: Ferret
   I must address a question here so as to clarify. First, science works on something called Risk- Benefit ratio. When an experiment such as mentioned above is conducted, the aim is to determine what are the factors accounting for transmission. To avoid the chances that the virus is a real threat, the chances of it getting into humans is avoided by using a model animal (That is why we use models after all and not humans). Ferret represents the closest model in terms of if it can be infected by the influenza strain under study. But mind you, ferrets are closest, not humans. We differ significantly. Somebody argued that if ferrets are not humans then why do the experiment at all. The answer is, it provides us with a road map of the possible dynamics which though doesn't match exactly still keeps us prepared. As an example, soldiers are first taught to fight the dummy enemies, not the real ones, though there is a huge difference between dummy and real. The benefit is very clear and high. In contrast, what is the risk? Virtually zero. There is containment and it is infinitesimally improbable that a ferret will sneeze into human face and the so transferred virus is human adapted enough to cause an infection.

Let me throw a question around. Is it that there never has been an accident in laboratory leading to problems? The answer is clearly a no. So how is it justified? Let us consider a fresh report again from this week in nature. CDC has reported that it had supplied anthrax to 2 other BSL-2 laboratories. Live bacteria for non published reasons survived the inactivation step, and were not detected before samples were sent out. If you had consider from the same report that that has been 727 incidents of theft, loss or release of Select Agents and Toxins in the United States between 2004 and 2010, resulting in 11 laboratory-acquired infections and no secondary transmission, that accounts to about 1.51% risk ratio. Consider, routine clinical laboratory practice and there is roughly similar risk ratio. Further, at least in this case, there is immediate remedial measures taken to quarantine the problem.

To conclude let me say that humans as a species has evolved to fear for small dangers in comparison to the vice versa. So when somebody puts an headline and says "Lab creates pathogenic strain", it is more feared and attacked than when someone says "Cure found". And media knows how to cash in the headlines, which potentially misleads people.

Fauci AS, & Collins FS (2012). Benefits and risks of influenza research: lessons learned. Science, 336 (6088), 1522-3 PMID: 22723407

Declan Butler& Brendan Maher (2014). Risks of flu work underrated. Nature News, 2014: 10.1038/511013a

Biosafety in the balance Nature, Nature News 2014. 510 (7506), 443-443 DOI: 10.1038/510443a

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