Saturday, February 2, 2013

“Not Again!” Op-Ed: I.A. Jeppson, MD

I have never been comfortable about making inferences about people’s subconscious motives, but my life experience makes me believe that the reason people give for opposing something is often not the real reason at all. I first noticed this when I got caught up in a situation precipitated by my research.

I had always been of the opinion that being honest with patients was important to maintaining trust. After all if we started lying whenever it was convenient (even if it was to the benefit of the patient) confidence in medical practitioners would decline and patients would think we told lies to make money. But I was working with patients who wouldn’t remember if I had lied to them. I reasoned to myself that in this situation being honest with the patient's family was really what was important, and this could end up helping not only the patients directly affected, but everyone. Still what I was about to do was nothing more than an elaborate ruse; at least as far as the patient was concerned.

However, the results of that experiment and those that followed steeled my resolve that this was something that needed to be implemented at every hospital and assisted living home. My enthusiasm spread quickly among my colleagues and the insurance companies agreed to pay for it, but there was a public backlash. My university was shutdown for a day when what was suppose to be a protest turned into a riot. Amid cries of “MY MOTHER DESERVES BETTER!” and “PEOPLE BEFORE PROFIT!” ten people had to be hospitalized and one was killed. After that I was not surprised when the death threats started coming.

The uproar that ensued even led to congressional hearings and proposed legislation banning the therapy. I ended up subpoenaed before congress and reluctantly subjected myself to the talking heads on television where I was called a cold-hearted scientist that couldn’t understand what it meant to be human, or that only someone with a financial interest could advocate such a thing. After media investigations found no evidence that I had any business ties to the robotics industry, and that I was not being paid to lobby for the insurance industry the matter was dropped, but not rectified.

Those who wanted my medical license revoked remained resilient. I could empathize with the people that were uncomfortable with the use of robots to trick patients into thinking that they were interacting with a human, but their outrage was only outmatched by their irrationality. Instead of looking at the matter at hand, the patients and their families, my personal life was scoured for anything that could discredit me. They somehow figured out that someone I had a physics class with in college (we hadn’t been in contact since) owned a robotics company. I was even called a racist because the robot used in my research was named Roberta (the inventor named it after his mother). The more reasonable opponents stated that all we really needed was to get people to come and spend time with people with dementia. But of course nobody wanted to pay for it and not many were willing to volunteer their time to do it. Not that I can blame anyone for not wanting to.

As an undergrad volunteering with dementia patients I saw the worst things I’d ever seen; mothers drowning in anxiety and depression because they cannot recall their children's names, people begging their long since deceased parents to come free them (the patients had to be restrained to the bed). Despite how widespread dementia was most people still had no direct experience with it. The only reason this therapy was not banned was because of the support of patients' families and even patients in the early stages of dementia. They understood that even with video chat their loved ones could not always have somebody with them.

The critics were correct about some things. The sitter-bots did not have souls and they had no empathy, but they were very good imitators. Before the bodies themselves were built the sitter-bot was nothing more than software that could talk to patients via an intercom. The results were incredible; all measures of anxiety plummeted, the rate of memory loss decreased. It appeared that having someone to interact with protected the brain from the still murky forces ravaging it. The rate of convalescence accelerated, enabling patients to be discharged from the hospital quicker. In a later study where games were introduced via a tablet computer the results were even more dramatic. Sitter-bot could continue conversing with the patient while playing the games and could even converse about the game itself; engaging in friendly trash talk and displaying mock anger when defeated. Through the games Sitter-bot could even identify cognitive weak spots and trends in cognitive decline. This data proved useful clinically and for further research. Soon Sitter-bots where developed that change game strategy to aid the patient therapeutically.

It was a shock to people that had never interacted with individuals with dementia that many patients came to believe that Sitter-bot was an old friend that they had known for years (often after just a few minutes of interaction). For instance, a patient of mine named his sitter-bot Evelyn and when he introduced Evelyn to his wife she became enraged and assaulted the tablet computer the sitter-bot avatar was on. I latter learned through the hospital's lawyer that Evelyn had been the name of the gentleman’s first wife. It became necessary to prep family and friends for the possible “side effects” of sitter-bot.

The improved moods of the patients were also reflected in their family members. All objective measures of stress decreased and from my own subjective experience with the families they seemed much more at ease. I wouldn’t go as far as to say they were happy, after all their loved one was slowly slipping away from them, but the situation was now less painful.

The loudest critics were those who worked in health-care. It is an open secret that much of the concern was about their jobs being replaced by robots and this was the litmus test. If a robot could be used to treat mental health, why couldn’t one wipe a butt, give a shot, or take a blood sample. Indeed all of these things eventually happened. I too felt anxiety about my own future caused by the exponential march of artificial intelligence and robotics, but when I look at the positive contributions these have made toward patients whatever befalls me is worth it. If we oppose a technology that can aid a patient because it will do us financial harm we are no longer healers. I am a firm believer that one should not waste their energy fighting the inevitable. I know from personal experience, when robots started being used to diagnose and treat common mild diseases, but one must prepare for the future. This needs to be recognized not just within health-care, but in society in general.

The transition to the use of robots in health-care may not have been seamless, but today you would be hard-pressed to find someone who would want to go back to the old ways. I am old enough to remember a time before autonomous cars. Young people today can not fathom how allowing individuals complete control over the movement of their cars was once considered an acceptable risk. Indeed, it does now seem absurd that we once preferred having a person operating an object that weighed a ton moving at 80 mph. Or how doctors once thought washing their hands before seeing a patient was a waste of time, because they had never done it before. That appears to be the nature of change, everyone bemoans it when it’s happening, but cannot imagine going back to the old ways once it’s done. I am of the opinion that health-care is at another one of these junctures.

The pharmaceutical industry entered its most profitable era after a consortium of the industry's biggest players developed an artificial intelligence software capable of scanning an isolated pathogen or molecular defect and then design a therapeutic. They split up the areas of manufacture based upon their respective strengths. This breakthrough should have heralded in a new age of personalized medicine; in a sense it did by taking into account a limited set of genomic information. The industry quickly developed a series of blockbuster drugs that they could control the manufacture of.
When the technology reached it’s limits instead of trying to improve it, resources were diverted to the legal, lobbying and marketing departments. Those who improved upon the technology were held up in court or sued into non-existence. Lobbyist insured that the patent office saw things from big pharma’s point of view. The marketers were needed for the few instances where a rival therapy made it through the gauntlet of lawyers and lobbyists. With their patents now about to expire the industry is feverishly attempting to have the laws re-written to protect their monopoly.

Now that their software is about to become opened sourced they fear improvements beyond their control will be made to it; allowing others to make a profit. They fear that improvements in technology have made it possible for drugs to be manufactured locally, on demand. Despite, the fact that this technology is by any measurable standard safe and dependable, big pharama is lobbying to have it outlawed; all in the interest of “patient safety”. As a society we should not succumb to the fear campaign of the pharmaceuticals industry. They may have convinced themselves that ‘thousands upon thousands’ will die if others are allowed to design and manufacture therapeutics, but the only evidence they have for this claim is their own motivated reasoning.

We live in a world where information is the infrastructure, and information changes rapidly. Never before has humanity lived in a world where the underlying structure that dictates how we survive can change so fluidly. It is hard to know which direction is forward, and as a society we must learn to be more accepting of the fact that many people will find themselves on a path that is no longer viable. If change is no longer seen as something menacing than the transitory periods will be less painful. Someone else's gain will not be another’s ruin and we can have an honest conversation, as a society, about the possible costs and benefits of the change in question. Those of us who work in health-care can become the paragon of this new paradigm. We can start by not letting our colleagues in the pharmaceutical industry fool themselves into thinking that they are now representing the best interests of patients. Not only are they not helping patients but they are also doing themselves a disservice. There was a time when we were reluctant to wash our hands to protect patients from infection, now we must get used to washing our hands of the past if we are to protect patients from ourselves.

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

Monday, July 25, 2011

Environmental Policy: Why Don't We Tax Pollution?

Switching taxation from income to pollution seems like the most obvious solution to most if not all environmental problems. After all it is widely acknowledged that if you want people to do less of something you tax it. The existence of sin taxes attest to the fact that policy makers agree that taxes inhibit undesired behavior in individuals. One of the main benefits to taxing pollution is that it can be applied to everyone equally, so that the government does not have to pick winners and losers as it does with current regulations and subsidies. The reasons that we do not tax pollution can be broken down into two categories: the practical and the political.

Practically speaking it is hard to put a price on the damage that pollution does and hence at what rate to tax it. However, even a rough estimate (and most likely an underestimate) would still give individuals and corporations an incentive to reduce their environmental foot print by finally putting a price tag on it. Additionally, implementing the tax would be no different from the common practice of taxing consumption except the tax rates would be based off environmental costs.

I suspect that the reason there is no serious debate in the United States about switching the tax burden from income to pollution is because politicians are boxed in by what they know. Both parties find taxing income a politically  convenient way of rallying their bases. Democrats like to argue that we should only tax the wealthy and Republicans fighting taxation altogether.   

However, it seems to me that Republicans would have the most to gain from promoting taxing pollution. It would play right into their narrative of not punishing hard work and ingenuity. I suspect that if Republicans could break their pathological aversion (and special interest pressure) to not tax anything they could gain a lot of mileage out of portraying Democrats as more willing to tax hard work and innovation then promoting a healthy environment.

J.A. Gibbons