An Interview With John Holdren

28 12 2010

Here is a link to a 2 part interview with President Obama’s Science Advisor and Director of the Office of Science and Technology Policy, John Holdren from the ScienceInsider, Science Magazine’s online Policy blog.

Part 1:

Part 2:

I especially like Part 2 because it’s a bit of a behind the scenes description of what it’s like to have John Holdren’s job. For example he stresses that one of his biggest struggles is “how do you keep the urgent from driving out the important?” Also, the timetable for which he must make decisions, “You rarely have the luxury of spending 45 minutes on something before something else interrupts…Even with a good staff, even with four strong deputies, the pace at which issues end up needing a decision from me is extraordinary.” Finally, I thought it was interesting to read what he thought the most significant publish findings were with regard to how it affected his office.


The Exposome: Finally, a way to measure nature vs. nurture.

15 12 2010

Today I attended The Sixth Annual Symposium on Predictive Health, Human Health: Molecules to Mankind at the Emory Conference Center.   The tagline was ambitious and meant to inspire:  “THE END of DISEASE, the BEGINNING of a NEW KIND of HEALTH CARE.” I was only able to go to Session V “Ethical Manipulation of the Human Exposome.”

The Exposo-wha??? Let’s back up.  Remember the genome? Remember when we sequenced the human genome 7 years ago, and people were really excited because this meant now we would not only understand what it meant to be human, but also how to predict and prevent every disease from which humans suffer?  Goodbye aging, goodbye sickness. Hello, ever-lasting health and answers to the previously unanswerable questions about humanity. Why didn’t that happen?

Well it goes back to nature vs. nurture.  You are the cumulative result of your genes and your environment.  Genes might give you a prediction about your susceptibility to developing diseases, but they rarely independently genuinely cause a disease. Given that environments are so complex and so varied from person to person, it’s staggeringly difficult to fully understand what the consequences of all these variables will be with your genes.  Enter the Exposome.  The exposome is a new body of generalizable data that explicitly talks about the intersection of your genes and your environment.  The exposome is a map of all your environmental exposures.

One example of the exposome is the metabolome, or a map of stuff your body has metabolized. A metabolite, represents something that has passed through your body’s cellular processes and can be measured by taking a blood, urine, or plasma samples. By collecting your metabolite profile, researchers are able to get a map of clues to your environmental exposures, and then possibly predict what diseases you may develop or what may have caused you to develop a disease. These data can be combined with your genetic data  to better understand how your body’s genes made you (in)capable of metabolizing agents in your environment (whether it be emotional stress or plant pesticides).  As you can imagine, your body responds to a number of agents at any given moment and can also be influenced by the current circumstances of your exposure (e.g. are you already sick, are you young, are you old, are you a healthy eater, etc). Actually, clearly isolating one culprit in disease causality isn’t as easy as it seems, even with the human genome sequenced. In addition, some things are metabolized and are quickly broken down, leaving barely a trace. Some things leave a longer lasting trace and others leave a temporary trace that you might only see at night or early in the morning.  Finding the right window to detect metabolites can also present a challenge.

Despite these challenges, we shouldn’t underestimate the power of combining the data from the Human Genome Project and now the Human Metabolome Database can potentially have amazing consequences on health care and the way we live.

At today’s symposium, some researchers stated that they were a bit puzzled about why they were asked to discuss the ethical implications of their work stating “I’m not an ethicist” or made statements that they felt their job as *public health* researchers was to put a wall between their research and how their data might affect legislation. They weren’t the first scientists who had their laundry list of excuses to not get involved with ethics. While I was a bit disappointed with these responses, I was glad there was interest enough to devote one of their sessions to ethical discourse.  Ethics sessions like these are necessary to ensure that public health researchers are not  blind-sighted by how their findings might actually hurt, not help the public if they don’t understand how to maximize the benefits of their work. While some interesting points were brought up during the session, I still wanted to know their thoughts, as public health researchers, on how this might actually change or lead to “a NEW KIND of HEALTH CARE” as inspired from their flier.

The Department of Health and Human Services (who is in charge of helping to determine your health and healthcare) have a mission to generate not only preventative, but personalized medicine.  Metabolomics could fit very nicely with these goals.  Metabolomics could tell you how to prevent certain diseases by unintentional exposure to toxins such as pesticides in the environment.  Metabolomics could also tell you how to prevent diseases by preventing behaviors that tipped your genetically vulnerable self into a state of disease.  It could revolutionize the way we live into healthier, longer-living, happier humans.

But what else could it do? What are other ways, the exposome could impact the way I live?

First, we need to better understand exactly how strong the predictive power of “metabolomics” for humans is.  Don’t these studies tell us more about association than actual causation? Many follow-up basic research studies will need to be done to confirm causality. And what  if my metabolic profile as an adult tells a sad story: my unfortunate environmental exposure profile has destined me to get a terrible incurable disease- what will I do with that information?   Should I just take the cyanide pill and warn my children not to make the same mistakes? Would the average citizen know how to interpret their metabolome results, or would hospitals now need to have a staff of genetic and metabolomic counselors?  Will my health insurance need to be informed of my pre-exisiting metabolome condition? Should my healthcare provider know this information?  After all, wouldn’t it help my doctors to give me better treatments and more personalized medicine?  Would I be required to tell my life insurance agent, my employer, or my employer’s lawyer? Extreme care will be needed to ensure that exposome data is secure and in the right hands.

How will this change the way we view “disease” and  accountability?  Environmental toxins like lead, or pesticides are not the only bad things you’re exposed to in your environment. Certainly everyone wants big business, Pharma, the military, and industry to be held accountable for the exposure that the public will unknowingly gets. What about the known, voluntary exposure to toxins?  The passive suicide cocktail of bad eating habits, smoking, and not controlling their stress or exercising?  This will  all show up in your metabolome.  Remember when drug abuse and depression were thought of as moral failures?  Sure some people still think this, but the popular mind has grown to understand that these conditions actually have a physiological substrate just like any other bonafide disease.  Let’s look at Parkinson’s disease or Alzheimer’s disease.  This is a disease where people don’t generally assume you have due to a moral deficit.  Parkinson’s disease is linked to unknowing, involuntary environmental exposure to pesticides.  What if it was linked to a series of voluntary choices?  Would we then say things like, “You gave yourself Parkinson’s disease?” How these data could and should be used will need to be clearly expressed to the public.

In fact, one could argue that all your activities in your history from your emotions to your ingestion of foods will be identified in your metabolome,  maybe even replace a fingerprint. Who should have access or own this information? Would certain exposome patterns be used to predict bad behavior?  If growing up in low socio-economic areas resulted in poor nutritional patterns, predicting subsequent criminal behavior, should preventative measures be taken?  The session at today’s symposium was about *manipulation* of the human exposome– should we manipulate this person’s exposome to try to then change or pre-empt his/her undesired behavior? Can this even be done?  These are the types of  basic research model experiments that are needed that need to be done in parallel to the human studies.  Not just asking, what are the associated changes in the exposome, but can we change them, and what would changing them do for people and society.  This information will also be required for making new health care policy changes. It is critical that the researchers doing this work be able to translate these data for public audiences. Researchers need to think more deeply about the ethical consequences of their work.  You don’t need to be an ethicist to do this, you just need to think critically and genuinely care.

Are scientists losing moral authority?

13 10 2010

Unlike lawyers and politicians, scientists tend to enjoy a bit of moral authority and credibility in the public eye. People assume that scientists work for facts-findings that are repeatably found, ruthlessly scrutinized and interpreted, and only then published with the highest of ethical standards. And naturally, all the while being driven only by their love of truth and advancing knowledge about the world we live in-a greater good type of thing.

This is why Climategate hit a particularly vulnerable public off-guard, “Whaaa?  I expect this from a slippery politician, but scientists talking about eliminating the competition!”  When I first heard about Climategate, I was actually a bit annoyed at the uproar.  I thought this is a bunch of people overreacting.  Sources of global warming are real, just look around you-if you can see through the smog.  I live in Atlanta, AKA “Car City.” My downstairs neighbors, a couple, own 4 cars and rent the condo beneath me.  They always have the TV blaring.  I also live next to a huge park with a big biking/running trail.  My previous neighbor owned a treadmill.

The public doesn’t understand how science works, I thought. And they probably still don’t understand that the issue isn’t whether global warming happens or not, it’s whether we the people caused it.  But I’ve become less sensitive to how science and personalities within science “work” (see previous post). Scientists are people too with all the same insecurities, poorly executed ideas, and dastardly plans for their competition. Now this doesn’t account for all of us.  I know many people who are interested in the truth, collaboration, real clinical outcomes, and overall reduction of suffering.  I do wonder sometimes if the mechanisms of being a scientist have created a bit of an obstacle course on the way to those goals. But on the other hand, I often wonder how our funding mechanisms may have created a culture where we actually succeed-not via toxic competition necessarily, but via healthy appropriation of funds to truly innovative science.  I’d like to share some of the challenges of being a scientist to non-scientists so you won’t be so caught off guard next time.

1. New graduate students and frustrated postdocs like to say that the big egos are a problem, but really everyone is big-time afraid.  Really afraid–of not being smart enough, not coming up with ideas fast enough, not getting funding for next year, not keeping up with the most recent findings and technologies, not publishing in time, and getting too old to keep up with all these fears. This pretty much never goes away. Most of these fears are taught in graduate school and then they typically stay with you throughout your career (if you plan on climbing to the top to having your own lab-which you’re also more than encouraged to do). Also, choosing a career outside of academia is gaining more acceptance, but is generally frowned upon by older mentors and even young aspiring scientists.

2. Graduate students and postdocs are the work horses of the university.  Science graduate students generally have their tuition waved and salaries covered by grants mostly from the government (National Institutes of Health).  Your U.S. tax dollars pay for us. Postdocs are *supposed* to spend  a relatively shorter time at the university. Although the “permanent postdoc” position is becoming more and more common. These grants all work upon strict timelines, generally between 1-5 years.  For example, once you’ve been a postdoc for 5 years (in the U.S.), you’re no longer eligible for independent funding (although things may change in the future).  This means your goose is cooked.  The idea being, if you didn’t make it by now, you’re probably not going to make it later.  This sentiment is pushed onto students, postdocs, and faculty throughout their academic careers.  Publishing high profile data helps you to keep getting that funding and people get desperate for these publications.  Without the funding you’re dead in the water. Graduate students feel a similar pressure.  While many are guaranteed funding from the university even if your adviser loses his/her grant, others don’t. In addition, many graduate students in larger prestigious schools (especially in the U.S.) are expected to have a couple of good publications by the time of graduation.  My advisor said one per year.  If your project isn’t working, you continue getting paid your little stipend, but you watch all your friends graduate as you enter your 7th year as a graduate student. Not to mention how underrepresented women are the longer you stay in the academic arena.

But maybe the more important question is *should* scientists have had moral authority to begin with? Let’s explore common perceptions of scientists

1. “Scientists know the “facts”. We should accept and memorize these facts.” Scientific inquiry may involve utilizing a set of given facts.  However, the process of scientific inquiry involves looking for a conceptual framework that can be used to explore the world and to draw connections about the world. They don’t really find “new” things about the world, they just discover new ways of conceptualizing the world. Moreover, scientists do not really have answers.  They generate more questions.  A good scientist’s career is more than finding a fixed endpoint answer, but actually discovering what they don’t know and how our current view of the world is incomplete. Being a scientist is very humbling in this way.  I never trust a scientist who always has all the “answers” nor one who is uncomfortable with saying, “I don’t know.”

2. “Scientists produce findings that can be repeated by everyone (at least all other scientists).”–See Case Study no. 1: Generally, each lab has criteria for repeatability within their lab.  When publishing data all methods are expected to be described in painstaking detail. Before most articles are published, they go through a review process by peers who maintain their anonymity.  When scientists submitt papers to academic journals, they can request a set of reviewers (ones that may look favorably upon his/her work) and even ones to exclude (people who authors know may be competitors-see Case Study no. 4).  The editors of the journal can choose to respect your requests or choose additional reviewers that you didn’t mention. If you’re famous, people tend to scrutinize your methods less. They assume that you know what you’re doing.  Also, if your “friend” reviews your paper, maybe they “trust” you and your methods.  This can be bad. What people often forget is that busy mentors usually are not directly monitoring the new graduate student or postdoc who is learning how to do the lab’s established technique on his/her own.  In addition, common lab methodologies even within the same lab can change/evolve over time, often for the better, without the lab head realizing this. Buy maybe worst of all, is that often people don’t take their peer reviewing obligations seriously. This is a free activity that one does dutifully out of an ethical obligation to the scientific community. Often it’s even considered an honor. While the lab heads are busy making sure grants are coming in and publications are going out, some of these things fall to the wayside. And then you have this erroneous data published out there for posterity.

3. “The priority of scientists is to advance knowledge.” Well, it may have started that way when the scientist was a bright new shiny graduate student.  But over time, publication pressures become the main topic of conversation.  How will be publish this? These data won’t get published in a very good journal.  The concern becomes less about creating a legacy of good scientists, but a legacy of good publications and survival. As most scientists know, 99% of the experiments performed don’t work or have inconclusive data.  And even with that 1% of success a very small proportion of those finding will become a readily translatable finding to public health or public concerns in the scientist’s lifetime if at all.   Scientists often believe in what they do, but they become distracted from the bigger picture.

Again, many scientists stay true to the moral authority society gives them, but these are the problems they face in the scientific community.  Scientific advances genuinely have and will continue to have benefits for public health and to advance knowledge, but the public needs to be more critical in their analysis of the deluge of scientific information hitting them from every possible media.  A good start is getting a little inside view of the actual “scientific process” and what scientists realistically can humanly do. Also, it will be important for scientists to have regular “morality-checks” and reminders.  This could include regular required ethics courses not only for graduate students and postdoctoral fellows, but also for new and old faculty.

Troubles for young scientists in academia

12 10 2010

Here are a few case studies of what’s happening in top research institutes around the world (names and obvious identifiers have been changed):

Case Study 1: I don’t want to be the first to disagree with Mr. Famous.

Dr. Somebody published finding that exciting finding, Activity ‘B’ was detected in the brains of Parkinson’s patients.  Dr. Famous published a finding that Activity ‘B’ was also detected in parkinsonian monkeys.   A large number of Parkinson’s disease researchers made the mad dash to replicate said findings in all of their research models, yet at best researchers have come up with weakly similar results or nothing close. Dr. Justasfamous’s postdoctoral fellow also cannot replicate the finding in monkeys.  The postdoc speaks to many researchers at SuperBig conference and find that everyone is struggling to try to replicate Dr. Famous’s infamous Activity B. The postdoc tells her advisor at lab meeting that she just doesn’t see Activity B in her research and mentions that she has personally spoken to several researchers having the same struggle.  The lab members discuss that there are several weaknesses in Dr. Somebody’s research and several desperate statistical analyses going on to attempt to polish data to show Activity B.  Another postdoc suggests that Dr. Justasfamous write a review to discuss these problems in the field thinking that it would be helpful for all the struggling researcher and even provide a bit of relief.  Dr. Justasfamous says that Dr. Famous is too much of an authority and it would be pointless to write such a review.  Meanwhile, the postdoc is requested to abandon his data.  No one will be willing to publish such contradictory data anyway.

Case Study 2: I need to publish no matter what it takes!

Dr. Newsome is a new postdoc in the lab of Dr. Noncon.  Dr. Newsome is expected to work with Dr. Leaving to help Dr. Leaving finish up his project while he moves on to his new position. Dr. Leaving agrees begrudgingly to help Dr. Newsome at first.  Dr. Leaving says that he used to be a computer programmer and that he knows how to create the results he needs without even collecting real data.  Dr. Leaving also says that he knows how to run experiments in ways to skew his data in the direction he needs. Dr. Newsome assumes Dr. Leaving is joking and is still learning the ropes of all the new techniques.  Dr. Leaving begins to get very distant and begins to work only in the middle of the night when he knows Dr. Newsome will not be at work or during inconsistent times so that Dr. Newsome must learn the techniques from other colleagues. Dr. Noncon eventually tells Dr. Newsome that Dr. Leaving is a bit difficult and that Dr. Leaving suspects that Dr. Newsome is trying to steal first authorship from him. Dr. Leaving came from a very small school and English is not his first language. He has worked very hard to find a good postdoc in the U.S. and now his second position. Dr. Newsome was surprised and had no intention of taking the lead as the primary author on these data, but Dr. Leaving is not convinced.  After Dr. Leaving has left, Dr. Newsome realizes that Dr. Leaving has taken all webdrive data, notebooks, and the external hard drive with him. Dr. Leaving sends his analyzed data back to Dr. Noncon who shows the data to Dr. Newsome.  Dr. Leaving’s data is surprisingly clean, much more straightforward than typically expected with the techniques used in the lab.  When reading over a draft of the manuscript, Dr. Newsome notices many methodologies listed that weren’t true.  When Dr. Newsome mentioned these, thinking they were typos, Dr. Leaving aggressively denied the errors.  Dr. Leaving had left only one document on the lab’s server and it had information that stated otherwise. In fact, Dr. Leaving was the author of this document. Dr. Newsome begins to suspect that his data might actually be fabricated, but has no proof.  Also, Dr. Newsome knows that Dr. Noncon needs this publication for a grant renewal.

Case Study 3: Mine, mine, mine!

Adam had been one of Dr. Bully’s favorite student’s so much so that he asked Adam to come with him to Big University to help he start his new lab (and enjoy the fruits of his new promotion).  When Adam began work with Dr. Bully, Dr. Bully told Adam to “pick” a research project.  Dr. Bully did drug addiction research and Adam decided that he wanted to study Chemical B and it’s role in drug addiction. Adam became very passionate about this project and was excited to continue this work at Big U. When Adam arrived at Big U, Dr. Bully’s personality changed.  In addition, Dr. Bully became very busy, and kept emphasizing that they were at Big U now and they needed to work hard to fit in.  In fact, Dr. Bully tried to get Adam to switch projects.  Adam was already having to take new classes and in helping to set up the new lab, he felt he had lost a lot of time and was eager to publish his findings. Dr. Bully asked Adam to give a department talk about his work where Dr. Bully attacked Adam’s project in front of a large group.  Dr. Fair especially took interest in Adam’s project and wanted to collaborate.  Adam eventually took his project to Dr. Fair’s lab.  Dr. Bully did not seem to be disappointed to lose the project telling Adam that, “You’ll never get a PhD” with this project. Dr. Bully did stay on Adam’s dissertation committee.  Adam’s project brought strong results. Dr. Fair and Adam wrote and submitted the paper to a top journal and entered the data as a chapter in Adam’s dissertation. While Dr. Bully was reviewing a draft of Alex’s dissertation, he called Dr. Fair.  Dr. Bully exclaimed, “At least some of these ideas must have originally been mine!” and demanded that he be listed as co-author. Dr. Fair and Alex felt this was not true and were surprised given that Dr. Bully had seen these data during Adam’s las committee meeting and said nothing. Dr. Fair added Dr. Bully to the list of authors, not because he believed Dr. Bully truly contributed, but to “keep the peace.” Dr. Fair felt his position was less secure as a new Assistant Professor vs. Dr. Bully’s tenured position.  After Adam graduated, Dr. Bully began pursuing Adam’s project using the “future directions” from Adam’s dissertation.  He did not offer to include Dr. Fair on future manuscripts.

Case Study 4: When Peer Review fails (taken from Emory ethics class).

Dr. Rolf and Dr. Janice work on similar projects but in two different model systems and have decided to co-submit their papers. Around the time that the two papers are published, a third paper on the same project is published in a different journal. A few months later, Dr. Rolf and Dr. Janice receive an anonymous email stating that the author on the third paper had been one of their reviewers and held up their papers in order to finish his.

This is not necessarily happening in every case, but most scientists would not be shocked from these stories.  In my next blog, I’ll address the issue of scientists and their weakening hold in society as a moral authority.

Women in neuroscience-why do they leave academia?

18 09 2010

My entering class of 2002 at Emory University consisted almost entirely women with the exception of maybe 2-3 men in a large group of maybe 15 or so people.  This was a complete fluke–almost everyone who received offers from Emory chose Emory as their top pick that year to the chagrin of many fine graduate neuroscience programs. In retaliation, other schools moved their deadlines up the following year. I felt lucky to have such a large diverse class,  like I had a better sampling of the population of future neuroscientists.

In a class full of intelligent, driven women, I wonder why most major university departments continue to be filled with men.  Maybe there just hasn’t been enough time you say.  But I think the problem may run deeper still.  According to the findings presented at the National Summit on Gender and Postdoctorate fewer women from the get-go are considering becoming a Principal Investigator (P.I.) and running laboratories.  I wouldn’t at all say that the men in my program were obviously more capable then the women in my program of running a lab. In fact, I’d probably say the strongest scientists were women-no surprise, when most of the class is women–the odds are in their favor. According to this same data set, equal number of men and women of equivalent age are in the postdoctoral workforce spending an equivalent period of time in postdoctoral positions.

The differences become unveiled when you look at the demographics of married men vs. women.  The married women with children are underrepresented in the workforce. According to a general census in 2004, 75% of women and 60% of men between 30-34 have children. Most of these women are not postdocs.  Do female postdocs have the resources they need to be postdoc moms?  What about childcare? According to this study, about 40% of male postdocs have a female spouse who does not work, whereas 8% of female postdocs have a spouse that stays at home. Further, 42% of male postdocs have spouses who shoulder the childcare whereas women on 16% of women have a spouse who can provide free childcare.  Why is childcare such a big deal?  Have you seen an average postdoc salary?  Well, I’ll give you a clue–working at Starbuck’s or Dollar General as a manager would give you equivalent if not more pay.

But all right, is this something that’s important to women?  Do female scientists want to have babies? 60% of female postdocs felt this was important. Yet 30% of women polled said they would be more likely to make concessions for their career than their spouses while 30% of male postdocs expected that their spouses would be more likely to make the concession.  A PhD is, after all, not an easy road. Once you get it, you want to make use of it.

These data show that most women want to have a baby and with the average postdoc age of 30-34, the clock is ticking. And as progressive as you’d think an educated woman with a PhD might be, their spouses don’t always tend to be equally progressive-meaning man men feel they should be working and not in the home.  However, these statistics may be changing.

Emory University is touted as being voted one of the “Best Places to Work for Postdocs”.  At the time women are graduating and making that commitment to go the P.I. route what kind of options do they have if they consider having children. Here’s what Emory’s  Office of Postdoctoral Education states (this goes for almost any academic institution though):

“…postdocs must use both paid vacation leave and disability leave before sequentially taking unpaid leave up to 12 weeks” and “By the Family Medical Leave Act (FMLA), Emory University postdoctoral fellows have a save position for twelve (12) weeks of leave for family reasons.”

Their HR website  states for faculty that they understand that having a child is a “natural process”, blah, blah.  However for subhuman postdocs, they also allow you to apply for “disability.” Semantics or not, this is really abhorrent and rampant sexism at it’s finest. But that’s just what this kind of insurance is called, you say? Yes, but this also implies having a child is not at all natural, but a “disability” that women bring with them into the workplace. What does the popular mind think of when hearing the term disability?  Broken bones, thrown-out back, something that’s not supposed to happen to your body. At least the FMLA ensures that you won’t get fired during this time. At least not for up to 3 months. Wouldn’t it behoove society to have it brightest procreating and raising more bright minds?

But here’s some food for thought :

U.S. Only Industrialized Nation With No Paid Leave For New Parents

That’s right, according to the International Labor Organization, you could get better maternity leave in Somalia or in the Congos as a postdoc or otherwise.

The second big issue reported by these data is lack confidence, which can be intimately related to the pressures of trying to raise a family.  Women report feeling inadequate in a number of characteristics deemed necessary to succeed including “competitive drive” and “aggressiveness.”  Academic success is directly related to publications and successfully getting funding.  As these are all extremely time sensitive, the “competitive drive” must translate into prioritizing the timing of grants acquisition and publications over the timing of starting a family.

This is not to say that every female scientist wants to have a baby, but it should be considered as “natural” to want one.  The overall dwindling female colleagues as one progresses through the ranks of graduate student to faculty does not inspire confidence is women floating in a sea of male dominated institutions. However, to be fair, while insecurities and the “imposter syndrome” are a problem for women, it also is an oddly prevalent sentiment in both male and female high-achieving academics.

We have a long way to go, but solutions to these issues are beginning to get addressed with forums such as the Summit on Gender and the Postdoctorate hosted by the National Postdoctoral Association and with the development of forums and mentorship encouraged by local chapters of organizations like the Association of Women in Science and Women in Neuroscience. Perhaps, the most important immediate, daily  line of action is to keep these topics in regular rotation in conversations at workplaces in academia. Throughout their training, women (and men) in science should continue to have open ongoing discussions about these concerns with both female and male role models. Most of all, these conversation should feel normal and natural rather than a feeling that alienates women from their peers.

Back to the Future: Stem cells

27 08 2010

What are stem cells and why is everyone up in arms about them? A very good FAQ can be found here on NIH’s website about stem cells and here for historical policy on stem cells and we’ll discuss it a bit more below.

Stem cells are what people are referring to when you hear the popular media talking about growing new organs in a dish.  The running idea is that stem cells, some types of stem cells, are a special type of cell that can be convinced to become whatever kind of cell you need.  So far, they have been successfully used in patients with diabetes to replace malfunction Islet cells that no longer know how to let your body store glucose, and are the reason why my friend Merriet survived leukemia in high school. These kinds of scientific innovations have revolutionized medical therapies and now scientists want to move onto the big guns, they want to re-grow your brain.  The precise model to use it in is Parkinson’s disease, a disease that does not become detectable to clinicians or even the affected patients until over 60% of a specific set of brain cells that produce dopamine and facilitate normal movement are long gone.

Parkinson’s disease (PD) is a severely debilitating movement disorder, characterized by slowed movement, muscle rigidity, postural instability, and difficulty initiating and terminating movements.  One Parkinson’s patients said that, “It’s like driving with the parking break on.” One of the most famous cure-for-PD crusader’s is Michael J. Fox, teen star of Family Ties and plucky hero of Back to the FutureMichael J. Fox has been an ardent supporter of stem cell research for PD and private grant support from his foundation has been critical for stem cell researchers given the ban of using Federal funding for stem cell research. Who knew he’d be driving that DeLorean back from the 21st century in a battle with zeroth century Christian faith.

But I thought Obama took care of that? Well, he did, sort of. But to understand this, we have to go back a little.  In 2001,  former President George Bush issued an statement that federal funds could be used for research on stem cells only if 1) stem cell lines were already established before August 2001 or 2) embryos that were initially for reproductive purposes, but were no longer needed. And of course, no one can receive money for giving up their embryos.  To be clear, it’s not that anyone has said “Stem cell research is not allowed.” They just said, you cannot use federal funding for it. Incidentally, this is an excellent way to kill a research project as NIH by far provides the lion’s share of funding for medical research. But in June 2007, Bush issued an Executive Order that “Expanded approved stem cell lines in ethically responsible ways.”

What does “ethically responsible ways” mean?  Basically, it means no stem cells from human embryos.  Stem cells from embryos are special in that their are “multipotent”.  This means they have the potential to be turned into any kind of cell.  After you were no longer just a sparkle in your parents’ eyes, you were a cluster of rapidly dividing cells.  Just a big mass of identical cells with the same genetic blueprints in each cell.  At some point, those cells choose what part of the blueprint to actualize.  Meaning some cells turn on genes to become or differentiate into skin cells, other become brain cells and some cells in the body actually stay in an on-call  undifferentiated state like in your bone marrow. If you capture some of these cells early enough, scientists have the technology to choose what these cells become. But this is not what Bush’s administration wanted scientists to study.  Bush’s order would provide federal funding for scientists to work on technology to make “pluripotent cells”. This means taking adult, differentiated cells and tricking them into going backwards into thinking that they have the potential to become many different types of cells.  This is an exciting area of research because this could mean that stem cells would be much easier to come by.  You could just scrape off a skin cells from any adult, even your own cells, put them into a dish, de-program them, and then reprogram them.  Additional work has attempted to utilize locally injected viruses that could reprogram your cells for you.  Unfortunately, in some studies this has led to cancer.  Also, “old” cells will naturally develop more genetic errors and mutations (essentially what cancer is).  Because these embryonic cells are brand new, they are relatively defect free. But the plus side for pluripotent cells is that they can be generated from the person who needs them, so you can have a better chance of avoiding rejection by the host’s immune system that you might otherwise see with the embryonic stem cells.

Okay, so Bush orders that you can do this research by “Expanding” it by only if it’s in “Ethically Responsible Ways,” read: only if it’s not using new human embryos (but cells isolated from old human embryos before 8/2001 are okay. Those are sitting in cell “banks”). In March 2009, Obama ordered an Executive Order carefully worded in response “Removing Scientific Barriers to Responsible Research Involving Human Stem Cells.” But the underlying barrier was not, in fact, removed says Judge Royce Lamberth because we didn’t go back far enough.  In 1996, the Dickey-Wicker amendment was passed by Congress and stated main points 1) human embryos could not be created for research purposes and 2)  a human embryo should not be discrimated against based on whether it’s in a uterus or not, meaning you couldn’t not put the embryo in danger or destroy it for research. The recent suit came from Dr. James Sherley, pluripotent (generated from adults) stem cell researche vs. Secretary of Health and Human Services, Kathleen Sebelius. Dr. Sherley, Nightlight Christian Adoptions, and others initially brought a failed suit to Judge Lamberth suggesting that Obama’s Executive Order would result in an unjustified competition with funds with those doing embryonic stem cell research. Nightlight Christian Adoptions, has a program called “Snowflakes”-a frozen embryo adoption program.

What did Dr. Sherley and others bring to light this time that caught Judge Lamberth’s attention. The first stem cells were derived from mice in the 80s and the first human embryonic stem cells were not derived until 1998. During the Clinton administration, NIH requested that funding for the development of embryos for human purposed be funded but Clinton recommended against this, but would permit funding for research of stem cells derive from remaining embryos from fertility clinics. Congress followed after with the Dickey-Wicker ruling came in 1996, 2 years before human stem cells were derived. The problem has never been that people don’t want to eliminate diseases or regenerate cells. The problem is that a law had been established that you could not “destroy human embryos for research” and Obama’s Executive Order hoped that it would get around this by saying that the scientists are not actually involved in the piece where embryos are “destroyed.”  Scientists can just take the isolated cells (isolated without federal research money) and research them (with federal money) said Harriet Rabb, Health and Human Services General Counsel.  While researchers were eager to move forward with embryonic stem cell research, they failed to realize the how legally vulnerable Obama’s Order was and some ethicists immediately saw this coming. And now, the Dickey-Wicker amendment and the Snowflake brigade come back to haunt us with the relatively simple logic, that you cannot get stem cells from human embryos without destroying them-even if you technically get someone else to destroy them for you.

While all this is going on, can we say whether replacing dopamine cells is actually going to help PD patients? The major problems for PD are three-fold 1) We have no cure 2) Even if we had a cure, we can’t detect the disease until most of those dopamine cells are obliterated and 3) With the exception of a small percentage of patients with genetically linked PD, we still don’t know what causes most case of the disease. What PD patients need are early detection and something that can reverse or halt the disease early. Right now, it’s actually not that grim.  PD patients have for the most part, excellent treatments for the motor symptoms of the disease.  As a PD neurologist recently told me, what does them in is falling (retropulsion, or falling backwards-most people fall backwards) and dementia. These are not features of the disease that are reversed with current dopamine replacement therapies.

And this is where basic scientists and clinicians often have different perspectives.  PhDs are going to look deeply into mechanism-most won’t think about using something therapeutically if it doesn’t work whereas often MDs don’t care how it works if it’s something they can prescribe to patients to give them some relief. Honestly, the latter is how patients generally feel too.  Stem cells geared at replacing dead cells is indeed valuable and has incredible medical promise for numerous medical conditions. That said, we must think of the bigger picture too.   If the quality of life of patients and their families is more impacted by dementia than by relatively treatable motor symptoms, it seems that these might be a more relevant brain target(s).  Once again, we must look at a disease not only piecemeal, but continually revisit a step back.  In this case, maybe optimizing the delivery of factors that can re-program cells to a pre-disease state before they die would be valuable.  For instance, once proposed hypothesis is that neuronal inclusions or plaques predict cell death staging throughout the brain in both Alzheimer’s disease and Parkinson’s disease. In the end, we hope that true ethical principals are driving people’s arguments and not a prideful religious stance. For now, we can keep watching to see what’s next for stem cell researchers and those who might benefit from this research.

Neuroethics Education

20 08 2010

Why is neuroethics not a required class for graduate students in PhD programs? Most current PhDs in Neuroscience probably couldn’t tell you precisely what neuroethics is.  We can consider neuroethics as a 2-headed coin.  One side of the coin would be the ethical implications of neuroscience research findings and technologies on society. The other side would be the study of the ethics of the human brain such as morality, ideas of truth, etc.  Typically these are expressed with imaging studies where parts of the brain “light up” when engaged in a thinking task (or even when engaging in “Thinking about Not thinking,” believe it or not). For the sake of this entry, let’s consider the former description of the ethical implications of neuroscience research.

In a recent conversation, my colleague suggested that to understand ethics, one needs a background such as readings in Kant and Neuroscience PhDs just aren’t familiar or willing to become familiar with that work.  I have noted that “philosophy” has generally been a derogatory word in my department, used to give a name things they could not explain and/or understand–“It’s too philosophical.” If you’re a scientist, you’ve no doubt heard this statement in passing, or maybe unfortunately, said it yourself.  But this is exactly the opposite of what philosophers do.  A good philosopher very critically and systematically tries to explain and understand things and the connections between them, and constantly questions adopted world views.   It’s actually not too different than the goals of good science in that regard. My PhD mentor used to say that good science “changes the way we think.” We’re all trying to describe the world, but perhaps in seemingly different languages. In a world where it’s possible to use brain imaging to study sacred values and to utilize new technologies that attempt to “wake” those in a minimally conscious state, it’s high time that we start learning to be bilingual.

But do we need to send our neuroscience graduate students to philosophy classes? Maybe sending aspiring neuroscientists to the philosophy department is not the answer. And maybe students don’t need to know all the names of the current philosophers, but they need to know the concepts and how these concepts are relevant to her/his research.  Currently, ethics courses are required for all pre-doctoral and post-doctoral fellows on grants from the National Institutes of Health (NIH).  While there are sometimes opportunities to take longer courses, programs typically offer a 1-2 day seminar style “Responsible Research Conduct” class which students begrudgingly attend. This is likely spurred by the mentor’s less than enthusiastic attitude about the student’s absence from the lab. However, most new graduate students enter science more than eager to make a meaningful contribution to society. Having graduate students engaged in the ethical and broader societal implications of their work should be a necessary supplement to neuroscience graduate training or even part of the dissertation defense-something perhaps some current faculty would not be equipped to discuss.  For some students with more “basic” science projects, this may seem like an impossible task. But, it’s important to remember that this is a critical mental exercise that will be necessary when applying for grants from agencies such as NIH, who will require that you to describe how this is relevant to public health.

But neuroethics has been around a long time, you say.  True, but not as a discipline. While addressing general bioethics concerns has been a congressional mandate since the 1970s, neuroscience as a discipline has made vast strides and refinements. In fact, with new neurosurgical precision, individual brain nuclei can be activated with electrode implants the diameter of two human hairs, and we’re now moving into a technological era where individual cells can be genetically color coded and individually activated with lasers.  The scale and intricacy of neuroscience questions make it a societal imperative to ask neuroscientists to push beyond comfortable boundaries and to dip a toe into the deep end of philosophical inquiry.  According to some, the neuroethics discipline is only 8 years old. The first meeting of the four-year old Neuroethics Society was held in November 2008. One of the leading Bioethics Journals, The American Journal of Bioethics now has added a regularly issued Neuroscience Journal to their family bringing the grand total of neuroethics journals to two. Only two major universities in the U.S. have Neuroethics Programs with even fewer opportunities for funding.  Fellowship programs are limited to “Bioethics” Fellowships or Health and Medical Ethics without a specialty for neuroscience research. Indeed, glancing over the “former fellows” of one major Bioethics Fellowship from the National Institutes of Health (NIH) shows that the majority of fellows were philosophy or public health PhDs, JDs, or MDs. Where are the neuroscientists in these conversations?

Today’s reality is that neuroethical examination needs to be more of a priority for neuroscientists.  As neuroscience and accompanying emerging technologies have entered into the realm of the popular media with increasing frequency, neuroscientists need to decide whom they want to be leading and influencing conversations about how to use this research. Neuroscience students should be having these conversations on a regular basis early in their careers, perhaps with regular interdepartmental journal clubs. The NIH has even issued the call for the development of “personalized” healthcare meaning instead of a one-size fits all therapy, future medical treatments will take into account a host of intersecting elements such as environmental, socioeconomic, and behavioral factors. Meaning, we will need to address medical care with a multi-faceted approach with specialist from a diverse set of disciplines. Fortunately, the generation of interdisciplinary studies have become more apparent in larger universities. For example, at Emory University research fellowships were previously available for interdisciplinary studies that intersect with neuroscience as well as current broader teaching fellowships where postdoctoral fellows and graduate students from a variety of departments teach a topic under a unified theme using each of their respective expertise.

Enthusiasm would also increase were more funding to go in this direction. And funding must go in this direction in order to add Neuroethicists to the academic roster. But is this a chicken or the egg question? How will the funds get appropriated in this direction if neuroscientists aren’t interested in proving that they need to do this work?  This is where society needs to make the call.  Engaging the public interest in having rigorous neuroethical inquiry in an important piece of this puzzle.  An educated public benefits everyone. And the public needs to be informed about recent scientific findings rather than it being delivered with flashing graphics and dramatic music.  They need to decide if they want to take a part in how neuroscience advances benefit them. Future posts will aim to continue explore these ideas and how to make neuroscience findings and it’s role in society more accessible to specialists and non-specialists alike.