Sunday, August 21, 2011

GOP Primary: Why Views on Evolutionary Theory Matter

Rick Perry’s recent remarks regrading evolutionary theory has drawn media attention to his support of intelligent design. In  response, Kevin D. Williamson of the National Review argues that politicians views on matters scientific are irrelevant. No one expects a politician to have knowledge of the esoteric debates & competing hypothesis within evolutionary theory anymore then they would expect them to have a working knowledge of econometrics or input-out-put analysis. However, it would be disturbing if a front runner for the presidency did not understand the concept of supply & demand. With the U.S. quickly becoming an information economy to have our leader not have a basic grasp of what constitutes a science & what constitutes philosophy is disturbing. Science is simply empiricism--the observation of nature. It may not seem that impressive, but it has done more to benefit humanity then any other school of thought. And to dismiss a candidates views on it is misguided.  

Frankly, I find Perry’s admission that he does not believe in evolutionary theory more disturbing then if he had simply said it was not something he had looked into. At least then there is the possibility that provided with the relevant scientific data he could draw a correct conclusion, but by taking a stand on the issue Perry is stating that he’s looked at the relevant data and came to the wrong conclusion. In fact, he even studied a science in college, but apparently it did not stick with him.

A good leader can not be an expert on every subject. A good leader knows when and where to seek council & to whom to delegate authority. The fact that he flat out rejects a fact & a theory that has been established for over 100 years calls into question his sources of information & the people he keeps around him.

My criticism has perhaps been aimed a little too much at Perry. Indeed, most of the candidates have shown their ignorance to science. The only candidate that has not is Jon Huntsman. Here is Jon Huntsman defending science in his own words:    

J.A. Gibbons

Monday, August 15, 2011

The Indomitable Antiviral:

A paper has recently published in PLoS ONE detailing a new antiviral that has the potential to cure any viral infection that is caused by a virus that produces dsRNA. The new antiviral has been shown effective against 15 different viruses among them the author notes dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. All signs point to the virus being nontoxic.
What really caught my attention though is a statement in the MIT press release:

Karla Kirkegaard, professor of microbiology and immunology at Stanford University [said] “Viruses are pretty good at developing resistance to things we try against them, but in this case, it’s hard to think of a simple pathway to drug resistance.”

Why is it hard to image a pathway for resistance? The antiviral is a combination of two protein domains one from an interferon pathway and the other from an apoptosis pathway. The “PKA dsRNA binding motif” is the domain from the interferon pathway & the second domain is a procaspase for initiating apoptosis. Both of these domains do not become active until late in the immune response &  most viral defenses act early in the immune pathway so presumably viruses do not have inhibitors for the binding motifs or most procaspases.  

Viruses have been under more selective pressure to prevent the activation of PKA and procaspases then to inhibit them once they have been activated. This is due to the signaling cascades typical of cellular signaling. The sooner it acts in the cascade the fewer the inhibitors it must manufacture. Even if the viruses evolve an inhibitor for the  binding motif or procaspases, since the antiviral appears to be non-toxic it could be applied in dosages capable of overwhelming the inhibitors.


While looking into this matter I found an interesting paper by some researchers who thought that they had come up with an antiviral that viruses could not evolve resistance to only to discover that they were wrong. They offer some insights into what went wrong and the characteristics they believe are required for an evolution proof cure.

J.A. Gibbons


Broad-Spectrum Antiviral Therapeutics. Todd H. Rider*, Christina E. Zook, Tara L. Boettcher, Scott T. Wick, Jennifer S. Pancoast, Benjamin D. Zusman.

Anne Trafton, MIT News Office. August 10, 2011. New drug could cure nearly any viral infection.

Viral Resistance Evolution Fully Escapes a Rationally Designed Lethal Inhibitor. Thomas E. Keller, Ian J. Molineux, Ian J. Molineux. Molecular Biology and Evolution. First published online: June 3, 2009

Monday, August 1, 2011

Future of Infection Fighting

Current antibiotics are fast becoming useless with few new ones in the pipeline. All is not lost though, there is much research going into finding alternatives. One of these alternatives is the old fashioned way of fighting infections. Before the discovery of effective and relatively safe antibiotics doctors often relied on what was called ‘antiserum’.  

Antiserum was made by filtering out the cells and clotting factors from blood and leaving the antibodies. The blood was usually obtained from horses that had been infected with the agent (or agents) that the antiserum was desired for. Though the source of the blood varied and whenever possible an animal that was not affected by the pathogen was used because they could receive high levels of the infecting agent without becoming ill and thus produce more antiserum. Antiserum was also obtained from people who had either recovered from the illness or were vaccinated against it.

As of 1921 the effectiveness of antisera varied greatly1. Since in most cases how exactly the antiserum worked was unknown it is impossible to make a conclusion for why this was so and whether or not it can be improved upon. It was believed at the time that one possible reason was that the antiserum was only effective against specific strains of a pathogen. Support for this theory came from the fact that when it was possible to identity a specific strain and provide an antiserum for that strain mortality was greatly reduced (compared to just giving one antiserum for all cases). Additionally, the effectiveness of various antisera varied from region and outbreaks. The fewer strains of a pathogen  found the more likely the antiserum would be effective.

Finding the source and solutions to the variable effectiveness of past antisera is critical in today's world were someone could become infected with a pathogen in New York but not show symptoms until in Hong Kong. If that pathogen is not common in Hong Kong the local doctors will not be able to aid that individual. Luckily, research  and use of antisera did not stop completely with the use of antibiotics.  

Today antiserum is still used and goes by the name immunoglobulin therapy. Currently used mainly for autoimmune, immunodeficiency or inflammatory diseases2. Today the antibodies are obtained from people who have been vaccinated.

Clinicians also depend upon antisera to fight many viral infections. Antisera is currently the recommended treatment for human rabies3  and is used to fight Hepatitis B infections4. Researchers have recently discovered a possible universal vaccine for ‘influenza A’ and possibly a way to fight an existing ‘influenza A’ infection by studying the antibodies produced by those previously infected with influenza or vaccinated5.

One thing is certain. Fighting bacterial infections in the future will be more expensive. Monitoring bacterial infections in the population will become more critical to ensure the proper antisera are available in sufficient quantities.

Though more expensive there are advantages to using antisera. One, pathogens will not be able to develop resistance to the antisera. Two, if the use of antisera against viruses is any indication there should be fewer adverse effects from disrupting local beneficial bacteria6.

Even if bacteria where not developing resistance faster then we can find new antibiotics there use is bound to become outdated. Physicians prescribe as narrow an antibiotic as possible but it is impossible to not end up harming helpful bacteria and antibiotic use has been linked to numerous health problems resulting form the disruption of bacterial flora. In the future it will be possible to scan an isolated pathogen and have a computer design and manufacture an inhibitor. As with the example of ‘Influenza A’ research for the design of these computer generated inhibitors will be informed by the mechanisms of effective antisera.  The technology already exists to determine if a molecule is a likely toxin7,8.Eventually, production will cease to be centralized as the technology becomes cheaper allowing for more local control and production of more efficient antibodies for every situation.

J.A. Gibbons

1. Principles of immunology. Howard Thomas Karsner. J.B. Lippincott Co., 1921

2. Current uses of immunoglobulin therapy and side effects  

3. CDC on rabies

4. Hepatitis B immune globulin and HBV-related liver transplantation. Akay S, Karasu Z. Expert Opinion on Biological Therapy.  2008 Nov;8(11):1815-22.

5. One antibody to bind them all. Marian Turner Nature News. 28 July 2011.

6. At least it won't hurt: the personal risks of antibiotic exposure.Stewardson AJ, Huttner B, Harbarth S.Curr Opin Pharmacol. 2011 Jul 18.

7. Towards rational molecular design: derivation of property guidelines for reduced acute aquatic toxicity. Adelina M. Voutchkova, Jakub Kostal, Justin B. Steinfeld, John W. Emerson, Bryan W. Brooks, Paul Anastas and Julie B. Zimmerman
Green Chem., 2011, Advance Article DOI:  10.1039/C1GC15651A  

8. Toward molecular design for hazard reduction—fundamental relationships between chemical properties and toxicity. Adelina M. Voutchkovaa, Lori A. Ferrisb, Julie B. Zimmermanb, c and Paul T. Anastas. Volume 66, Issue 5, 30 January 2010, Pages 1031-1039.
Advances in Green Chemistry