Brains & Machines

Its sometimes hard for me to put into words the visceral pain associated with getting a grant rejected from funding agencies like the National Institute of Health (NIH).  The feeling is somewhere in between getting kicked in the crotch and seeing your high school sweetheart kissing another guy.  The pain and sense of betrayal runs deep and bitter.  For those who don’t do science, a little background is necessary.  For any scientist, engineer, or physician running a lab, the way we get funding to answer scientific/technical/medical questions is by making a proposal to the government and then having some agency decide on whether it’s worth paying for.  Sounds reasonable.  Well maybe, and then maybe not. 

Lets look at it a different way.  In thinking about  future success of the nation, we (or the government really) have to decide how to allocate resources that best serve American interests.  Typically, those resources are measured in dollars.  How much do we want to pay for health care?  For research? How to structure taxes to optimize our competitiveness in the global economy?  Thus, when thinking about funding scientific research,  the congressional luminati have to measure the value of a scientific advance  against all the other national needs. Obviously it’s not a simple task.   One problem with the current political equation, however, is that money is not are only resource.   A common occurrence through economic cycles is that when the economy is down, the general assumption is that we need to tighten our belts and agencies like the NIH are just going to have to get by with less.  That is a more costly choice than people realize.  Especially as we approach the fiscal cliff.

Since we are talking about science, lets do another experiment.  Lets imagine what would happen in this situation. The US has gone into a substantial recession (after say an increase in tax rates and substantial cuts across government agencies – aka “fiscal cliff”).  There is an enormous need for jobs and innovation to recharge the economy.  Now what would happen if we took 90% of the scientists and engineers and locked them in a room to prevent them from doing what they do, which is developing new insights into nature and creating new technologies based on those insights.  That general output is what creates stuff ranging from the internet to MRI scanners to new drugs for cancer.  The impact spans every aspect of the economy from energy to medicine.  Alright, so that final 10% who we do let work, they can only work in their labs each time they are able to successfully create a house of cards five feet high.  If it falls they need to stop what they are doing and rebuild it.  So in sum, most of the brightest people are imprisoned, the rest are doing busy work.  The ultimate impact on the economy would be that nobody is creating stuff that American companies can sell to compete in the global economy.

As it turns out it’s not an experiment.   The current grant structure has funding levels at about 10 percent or below.  So 90 percent of scientific efforts are going unfunded. Worse, those people running labs and trying to get money to support them are spending the vast majority of their time writing grants to take a crack at the 10% funding line (building the house of cards).  Taken together the vast majority of the human capital that America has in science is being wasted by lack of funding and endless busy work to try to get funding.  Put another way, if the scientist only has a 10% chance of success at getting a grant, and it takes him or her months of work to put that grant together, they would be better served by cutting grass or cleaning dishes where they are paid an hourly rate and then taking those proceeds and playing at the roulette table.  If they played red every time they would have a 50% chance at getting a return on their effort.  For the average scientist this is a daunting scenario to build a career on. Furthermore, this is not a recipe that will deliver American innovation. 

At the heart of the matter, money is not the only resource in America.  It’s certainly an important one, but not the only one.   It is hard to put a price tag on lost opportunity, but saving some money now on research will substantially impair heavily in America’s current scientific environment today and  will be even worse for our competitiveness in the future.  I hope that as Democrats and Republicans attempt to craft a compromise for fixing our ballooning deficit they understand this.  

A while ago I received an email from a graduate student telling me I should, in essence, choose between academia and commercialization.  That, in his words, “trying to go in both ways will make people in the academic circles concerned.”  He was in fact right. Often trying to do translational work and basic science can often raise eyebrows amongst members of the strictly academic community.  Why is that?  Well let me try to encapsulate some of those arguments.  Here are a couple of them.  “Knowledge should not be constrained or controlled, thus patenting your discoveries is antithetical to the mission of science.” Another. “Having a financial interest in the results of your research could alter your objectivity and thus corporations and business should never be involved in the scientific process.” A lot of these statements are made with the best ethical intentions.  They are, however, all misguided. 

Lets start with a very fundamental principle of why we do science.  First and foremost,  we pursue an improved understanding of nature to improve the human condition.  The scientific method is one of the greatest inventions by man to pull our species out of a million year history in the wilderness. Put simply, science serves humanity, not the other way around.   That principle can be stretched pretty far, ranging from why we study fungi to astrophysics, but ultimately all of them are there to enhance our lives in one way or another, period.  So if we take that core principle – science serves man- as our north star it can help guide us through some fairly confused issues in science and medicine.

The mandate for the National Institute of Health is to promote the health of the citizens of the United States.  The NIH is one of the dominant funding sources of American science.  Now an important question here. What happens to those scientific discoveries?  How do they get translated  (big buzz word at the NIH) to create drugs, medical devices, new imaging techniques that improve patient’s lives in a myriad of ways? Simple answer - Industry. This is not a function that is performed by medical schools, research institutes, or government agencies. Companies need to invest extraordinary amounts of money to the tune of tens to hundreds of million dollars to bring a discovery to something that is safe and effective in the treatment of disease.

Now let me introduce another very simple principle – economics.  Finance and the exchange of money are the fuel for powering human activities.  Again, to be overly simplistic about this, we need money to do things.  This is not a moral situation.  Money in and of itself is not an evil, no more than gravity or other natural forces are evil.  It is a force that strongly influences human behavior like gravity governs the movement of planets.  So when thinking about translating discoveries to clinical treatments, one has to consider financial forces at work. Why? Because it is really expensive.

Alright, given those two concepts,  what is a scientist to do when he or she finds something that could significantly improve human health. Say Dr. Scientist has discovered something that could treat a disease.  Now what?  How do we get it to humans?  How does Dr. Scientist turn this into a therapy that grandma can take?  Well someone, or a group of people, have to test the safety and efficacy of that concept.  Typically this involves clinical trials that have to pass through the Food and Drug Administration.  All of this costs money and most of it is NOT paid for by government.  Rather, it’s a cost because of the government. Moreover, this is a risky process that that may fail at multiple steps along the way. Maybe the drug has a bad side effect, maybe it doesn’t work in humans, maybe maybe, maybe.  So who is going to pay for this? 

Here is where market forces take hold.  If there is a big need, there may be the opportunity to sell this therapy and generate a profit.  So investors need to put money together to fund this idea.  A key here in these early stages is to ask what are they investing in? An idea?  If it takes ten years and a hundred million dollars to develop this concept, what if somebody else tries to copy all those efforts and sell something identical right before the original group gets to the finish line?  That is not only unfair, it also is financially too risky for anyone to consider as a reasonable investment. So there needs to be some guarantee that if someone is putting all this time and effort into a high-risk idea, that when the idea proves successful they can benefit from their hard work.   This is what a patent is.  It essentially allows for investors to reduce the risk of putting money behind a good idea.  It is the American patent system that was drafted into the Constitution that has driven innovation in the US like no other nation.  Is it limiting the dissemination of information? No, quite the opposite; by providing a limited monopoly on the idea for twenty years, the idea has to be fully disclosed in the patent so that it can be used for the good of the public after the expiration of the patent.  So returning to fundamental principles – science is there to serve man – creating a system that facilitates the development of an idea into something that improves health is fundamentally moral.  Not having these guarantees, essentially allowing an anarchy and predatory situation where someone can unfairly capitalize on another person’s ideas would actually lead people to be more secretive and unlikely to invest in risky concepts.

Next irrational fear —  scientists or physicians should not have a “conflict of interest” (another big buzz word) in their  research.  Concern here is that the opportunity for getting financially rewarded for creating and translating a medical therapy would lead the individual to falsify or misrepresent their work.  Therefore, if they really stand to benefit they shouldn’t do the research.   There are several issues here that need to be addressed.  First, the idea that to maintain one’s objectivity you have to remove all interest from the task.  Quite frankly, when really looked at closely, this is just silly.  Humans do things because they have an interest in doing them. If they didn’t they would be something akin to a zombie. Now financial interest is simply one thing that motivates humans.  For the scientist,  getting published in a high impact journal, getting promoted to professor, being recognized for one’s accomplishments are also potent motivators.  Because a scientist is motivated to succeed should not be considered a detraction from the quality of their work whether it be financial boons or professional accolades.  

Now will a small subset of people make unethical choices for a potential gain? Yes they will.  This brings us to another point of social cost.  Which is better – try to eliminate the actions of a few bad apples by making policies that make translation harder for everyone, or create scenarios that reward people for achieving  positive medical advances with the knowledge that a small percent may cheat.  Again put more simply, prevent a whole lot of good things by avoiding a few bad things, or have a whole bunch of good things happen knowing a few bad events may occur.  At the end of the day, there is no free risk free scenario.  But the question is which risks are we willing to tolerate.  Once again considering the two fundamental principles that science is intended to serve man, and that market forces govern human behavior, it is better to create policies that enable market forces to support socially positive outcomes (more translation advances) rather than  creating policies that reduce that social motivation. 

Now in advocating rewarding people for socially positive scientific and translational efforts, does that mean that we simply shrug our shoulders if someone violates ethical standards in their scientific research for some gain? No absolutely not.   If someone were to falsify data in a clinical trial for a therapeutic for financial gain they should be criminally prosecuted.  This act is in effect a form of malicious intent no different from fraud, insider trading, or even possibly assault.   If a drug is falsely represented and patients take it, which results in a physical complication, the person or persons should be held criminally liable.  Today, falsifying data leads to social and professional penalties (loss of a job, retraction of a paper, etc) but nothing that actually speaks to the justice of the harm they could or actually caused.   Taken together, when a scientist is translating a technology to a clinical therapy the stakes should be raised for both the positives and negatives.  Namely, if they do something that helps people –reward them handsomely.  If they behave unethically – punish them severely. In this scenario we are likely to properly motive the right people, and halt the unethical behavior. This is likely  better than the current scenario that prevents appropriately motivated and successful people from getting rewarded, and not really punishing the others when they transgress. 

            Time and again I have seen the debate over nature versus nurture unfold in the courts, in media, and in classrooms when people try to articulate  why  a person committed a crime.  Was it because they are a terrible person with malign intentions or where they the result of a lifetime of poor nurturing and abuse that manifests as a learned antisocial response that absolves them of their culpability.  It gets to the notion of how free is our ability to make choices. What are the limits and how much are we governed by our environment such that we are nothing more than pin balls following a path determined by the bumpers of events and life experiences. 

            I would argue when considering our ability to choose freely, that the choice is heavily taxed by our biology.   As an analogy, if you put me on a football field  I can easily choose which direction that I want to walk in.  Well sort of – I can move left, right, forward, and backward.  Those choices come at a relatively small cost. What about moving up and down.  I  can  go up and down, but it’s a whole lot harder.  To go down I am going to have to swing a pick ax and push a shovel.  To move up I am going to have to learn how to fly.  Not technically impossible but very very hard.   Similarly, I think that our ability to choose certain behaviors given the physical and social realities that a person lives in also create bumpers that, while not impossible, make it very very hard.  As an example,  the question raised was why didn’t any one speak put against Hitler or Saddam Hussien in their repressive regime to stop moral atrocities from happening.  In isolation the choice seems quite easy – say that killing people is wrong.   That is in isolation when there aren’t things like the very real social gravity pushing the individual to conform, to not ask questions, to agree.   That social gravity is equivalent to the gravity that holds us the earth.  The force of it is very hard to resist.  Hence when we do see examples of people moving against it – we can understand the true herculean task that it was to accomplish.  It is the same reason that we celebrate the accomplishments of the Wright Brothers in their ability to move beyond the physical constraints of our bodies.  Henceforth, the choice to fight gravity becomes that much easier.  This also true with social justice.   Similarly, when people like Gandhi and Martin Luther King are able to first break the social gravity that compel immortal behavior, such as racism, they make it easier for all the rest of us.

            So when we talk about our capability of free will, yes we can make any choice that we want. The question is do we have the strength and will to pay the price that decision requires. 

I am excited to say that my novel, RedDevil_4 was recently signed with Tor Publishing. The same group that has published Isaac Asimov, Frank Herbert, and Orson Scott Card.  Below is the books summary. Hopefully it will be coming out in the summer of 2012. Stay tuned.

RedDevil_4 by Eric C. Leuthardt, MD

 In the near future, when mind machine technologies have become commonplace, a series of shocking and brutal murders reveals that this leap in human capacity comes at a price that threatens the very survival of the species.  

 Dr. Hagan Maerici, a neurosurgeon and scientist, finds that his high profile patients are ritualistically killing people. As they show up in the hospital, Hagan is thrown together with two detectives as he tries to unravel their bizarre neurological syndromes and avoid suspicion as the culprit. Hagan must risk his life’s work, an artificial intellect named Omid, to try save the next victim and his own freedom. But as they get closer to an answer, Hagan realizes that the illness affecting his patients is the result of a mistake he made years back - an error that now stands to wipe out millions.  This rapidly emerging peril leads Hagan, his AI Omid, and the detectives through a treacherous gauntlet to prevent catastrophe.  Ultimately, they find that both the problem and its solution reside in the ambiguous interface where the boundary between man and machine has become blurred.

 Currently, human civilization is approaching a tipping point.  Brain computer interfaces, nanotechnology, cloud computing, and biotechnology are pushing to fundamentally alter the way that people will interact with machines and with each other. The very fabric of human experience is poised to change once the human mind becomes accessible. As with every major scientific revolution, mankind will be confronted with a new set of unforeseen challenges.  As a leader in the field of neuroprosthetics, the author grapples with the social, ethical and legal ramifications of this radically different world in this futuristic thriller.

 Just as Michael Crichton’ Jurassic Park captured the public’s imagination and fear of the impact of genomics, RedDevil_4 taps into a similar fundamental fascination and anxiety about science’s dawning capability to penetrate the most core aspect of being human – one’s thoughts. The book also explores the timeless theme of man’s connection to his biological and technical creations. As an ardent fan of Isaac Asimov and Frank Herbert who also studied theology as an undergraduate, Dr. Leuthardt sought to build a future world that reveals the complex psychology, cultural motifs, and religious resonances that define the relationship between creator and created. 

What is the one thing that a patient with epilepsy wants?  Is it for the seizures to stop? To be off the medications?  The top of the list that I hear time and time again is this – to be able to drive a car.  Without a doubt seizures are dangerous and socially debilitating (image going about your day to day life with the thought of abruptly losing consciousness).   Due to their epilepsy, these patients are legally prohibited from driving because their seizures put them at risk for getting into an accident.  At first glance, that of course sounds inconvenient, but to my patients it often means everything.  The question is why?  Why is driving so important?  I think as we delve into the answer it tells us something about how humans have evolved in the modern era.            

To answer the question I would cite some work done by Atsushi Iriki’s lab at the Riken Brain Science Institute in Japan.  He did some interesting experiments with monkeys in which he trained them to use rakes to pull a morsel of food toward themselves while recording brain activity with electrodes.  The electrodes were in the post-central gyrus, a part of the brain involved with sensory perception as it relates to our bodies.  So if someone touches your hand there will be increased neuronal firing in that part of the brain.  Similarly,  Iriki identified neurons that would start to fire when you touched the monkey’s hands.  After they were trained to use the rake when they touched the rake, the same activity appeared. Thus, according to that monkey’s brain, in a very real way that tool became a part of his body.

What does that have to do with epileptics driving cars?  From monkeys to humans, the tools we use quite literally become a part of who we are.  We perceive them as a part of our body.  One of the most fundamental tools in modern society is the automobile.  It is our new legs in a mechanized environment. Actually, its probably more than that – in addition to mobility we associate cars with our lifestyles, economic class, and personalities (people who drive Hummers are usually quite different from people who drive Minis)  Thus, when a patient with epilepsy looses the ability to use a car, he or she has a lost a part of themselves.  Essentially, they have  lost a physical expression of their persona and, more importantly, they have lost   their ability to navigate a specialized environment where most resources are beyond  physical walking  distance.  Interestingly, a patient whose legs are paralyzed have more independence and freedom in the world at large than a patient with epilepsy.  Whereas four hundred years ago in a small medieval village, the exact opposite would be true. From a personal standpoint as a surgeon who treats spinal cord injury and epilepsy, whenever I am able to intervene and recover leg function or cure their seizures, the patient’s psychology of being returned to independence is almost exactly the same.

Please don’t confuse my praise of a car as materialistic.  Rather, the point here is to show that the boundary of what we call our bodies (according to our brain’s physiology) is more gray than what we would like to believe. Going into the future new “body extensions” will be cropping up with increasing speed and diversity. How many people today feel handicapped without their smart phones, their ipads, or their laptops? More than materialistic desire, the adoption of ever increasing capability is part of how we as humans are built.  There is an innate cortical plasticity to take on new functionalities and incorporate those elements into our cognitive model of “me.”  It is this cognitive flexibility that allowed our ancestors to first use tools (such as a rake) to advance our ability to survive and proliferate.  Interestingly, with the advent of novel human machine interfaces (iphones, cars, and brain computer interfaces),   we will see the emergence of new and more impressive capabilities and the emergence of new disabilities when those capabilities are taken away.  Thus, you never get free lunch – even if you get it with a rake.