Applicants for these competitive fellowships must hold an MD and/or PhD degree. Scholars selected for the Vancouver-based program will receive both travel support and a monthly stipend. Openings are currently available and applications will be reviewed upon receipt.

To apply, please submit a short statement describing your interest in the scholarship and proposed project, a cover letter and CV c/o Janice Matautia: matautia@mail.ubc.ca

I reviewed and thoughtfully considered the data, clinical information, and analysis provided by Center for Drug Evaluation and Research (CDER), and I agree with the Center that there is adequate and reasonable, well-supported, and science-based evidence that Plan B One-Step is safe and effective and should be approved for nonprescription use for all females of child-bearing potential.”

“However, this morning I received a memorandum from the Secretary of Health and Human Services invoking her authority under the Federal Food, Drug, and Cosmetic Act to execute its provisions and stating that she does not agree with the Agency’s decision to allow the marketing of Plan B One-Step nonprescription for all females of child-bearing potential. Because of her disagreement with FDA’s determination, the Secretary has directed me to issue a complete response letter, which means that the supplement for nonprescription use in females under the age of 17 is not approved.  Following Secretary Sebelius’s direction, FDA sent the complete response letter to Teva today.  Plan B One-Step will remain on the market and will remain available for all ages, but a prescription will continue to be required for females under the age of 17.

Art Caplan, Director of the Penn Center for Bioethics, came out fast and furious with his criticisms – bad policy trumping good science.  Writing in the New York Times, Daniel Carpenter, Professor of government at Harvard put out a call to make the FDA an independent body, free of government oversight (or, as some would have it, interference).

These are all interesting matters, but there is a larger issue that surfaces in a single paragraph in Carpenter’s op-ed piece that is worth pondering.

Critics of this idea will point out that the F.D.A. is equipped to review drugs from a health and safety point of view, not from a moral one. This is a reasonable point. But it doesn’t follow that the secretary or president should have a blanket veto over its decisions. Congress could easily establish a law providing for separate bioethical review.

Regulatory agencies such as the FDA have traditionally evaluated drugs on the basis of safety and efficacy alone – they have generally shied away from making determinations about drugs using anything but the raw data to guide their decisions. Such was clearly the case in the evaluation of Plan B One-Step, as FDA Commissioner Hamburg said:

It is our responsibility at FDA to approve drugs that are safe and effective for their intended use based on the scientific evidence.  The review process used by CDER to analyze the data applied a risk/benefit assessment consistent with its standard drug review process.  Our decision-making reflects a body of scientific findings, input from external scientific advisory committees, and data contained in the application that included studies designed specifically to address the regulatory standards for nonprescription drugs.

I accept that the criticism in this instance was aimed at heavy-handed meddling by Secretary Sibelius. But what about the larger issue? What about including bioethical review in the drug approval process?

There is probably little need to consider the impact that drugs have on society at large for most drugs that the regulatory agencies deal with, but for some, including the nuanced bioethical issues may be important. In the field that I know best, cognitive enhancement, it is clear that both experts and the public are divided over whether such drugs should be made available, and if so, to whom and how (exactly the kinds of issues that came up in the Plan B One-Step case). The deluge of lifestyle drugs that are anticipated to arrive in coming years represent a whole barrel full of headaches that regulatory authorities will be forced to contend with. Bioethicists have wrestled with these issues, and are in a position to provide thoughtful advice on the implications of one course or another. The problem is this: who decides? It is one thing to bring in a panel of scientific experts to evaluate the data on drug efficacy and safety, and it is quite another thing to bring in a group of bioethicists to opine on the pluses and minuses of introducing a particular drug in a particular way. As with people in general, bioethicists arrive with a variety of political positions, and the outcome might depend as much upon the choice of experts as anything else. Not so good.

And that is where my modest proposal comes in. Increasingly, bioethicists are carrying out empirical work – querying the public about their attitudes towards one issue or another. [Full disclosure: empirical work of this nature is the centrepiece of what we do here at the National Core for Neuroethics, so admittedly, my modest proposal is self-serving.] This empirical work produces data, and such data could be called upon as part and parcel of drug evaluation in cases where it is appropriate. The issue of who would listen to and adjudicate the data remains a thorny one, but moving from elite opinion to well-designed studies of public opinion would be an important step forward.

For a list of references on the subject, visit here

Geron justified its decision on grounds of “capital scarcity and uncertain economic conditions” in its official press release. These concerns were reiterated in their webcast, which explained their steps along the lines of stakeholders’ interests: Geron had to keep the highest return for stakeholders in mind. The company suggested that the resources would now be used for advancing its in-house cancer trials (phase II).

Patient advocates were disappointed with the decision, particularly in relation to the motivations for the decision. Daniel Heumann was quoted by the Washington post as saying: “”I’m disgusted. It makes me sick. To get people’s hopes up and then do this for financial reasons is despicable. They’re treating us like lab rats.””

Geron seemed to be less concerned about the patient population or the participants. In their webcast, they argued that first and foremost, the trial was a safety trial. The four patients, who had been enrolled and ‘treated’, had provided consistent data that no safety issues arose. Enrolling four more patients and finishing the trial, one of the Geron representatives suggested, would perhaps not even lead to incremental data. Second, the initial four patients had ended their treatment, as treatment in the Geron trial consisted of a single injection with a stem cell-based product. Monitoring of these four patients would continue, even upon termination of the trial. Finally, the company proposed that the individuals, who had consented to partake in the trial before the halt was announced, could still get their injection if they so desired. Geron emphasized that no one would be cut off from treatment. Interestingly, in response to being asked what the company would say to patients, its representatives answered that Geron had no direct contact with the patients; the announcement would have to be done by the clinics in which the trials would take place.

Geron also emphasized that it hoped to find a partner so that the trials could be continued under a future sponsor. The company is quoted here as saying “hoping not to let anyone down”, “hoped the program to have a future” hoped that “the field would continue to move forward” and finally Geron suggested that any hope would be welcome.

Whether the comment about patients being lab rats is fair, still remains a question for answering. Some scientists said that the halt was not surprising since the underlying science was perhaps not completely worked out. Robert Lanza, in the New Scientists, suggested for example: “It was a very difficult choice to go in and treat spinal cord injury…There was considerable concern in the scientific community that that might not have been the ideal first indication.” Similarly, John Martin, in the BBC news said: “The Geron trial had no real chance of success because of the design and the disease targeted. It was an intrinsically flawed study. And for that reasons we should not be describing this as a set back.” If these scientists are right, the comment about lab rats seems to gain some support, even when it is argued that the generated science is not necessarily lost. Furthermore, some support for this point of view could be drawn from the ethics literature. Here arguments have been put forward that the chosen patient population would perhaps not be the most ethically sound participants; whether the sub-acute patients could provide informed consent would be ethically contentious. Could the participants therefore be framed as lab rats under an ethical framework?

I’d like to identify here a further concern about participants as lab rats, from an ethical point of view. My concern is Geron’s offer to provide an injection to those who had already consented to participate in the trial (let’s call them ‘consentees’). Geron seemed, at least indirectly, to admit that their participation would not lead to incremental data. This makes the consentees’ efforts, arguably, futile. Consentees would not generate valuable data, while being exposed to risks (of an injection generally, unobserved long term effects etc.) The offer for ‘treatment’, as Geron euphemistically phrases the research participation, thus makes me raise my eyebrows; would it be ethically sound to inject these patients purely based on their consent? “Yes, I want this injection”. But on what basis can Geron justify this injection; it does not seem to be research, nor is it treatment either. The stem cell doses would was deliberately so low to generate as little effects as possible. Basing the injection on a principle of compassionate use seems also to be out of order in this experiment. Would it therefore be an injection of hope? And if so, what does this show us about participant’s therapeutic misconceptions? Perhaps an injection would reduce a consentee to the lowest status for lab rats: the leftover lab rat. To paraphrase what the injection would mean; ‘We can give you the injection, but it is only because you asked me to… It will not benefit anyone; neither you, nor science overall’. Indeed, arguably, this would certainly go towards treating the SCI injured individuals as lab rats.

“Besides outlawing all abortions, with no exceptions for rape or incest or when a woman’s life is in danger, and banning any contraception that may prevent implantation of a fertilized egg, including birth control pills, the amendment carries many implications, some quite serious.”

“It could curtail medical research involving embryos, shutter fertility clinics and put doctors in legal jeopardy for providing needed medical care that might endanger a pregnancy. Pregnant women also could become subject to criminal prosecution. A fertilized egg might be eligible to inherit money or be counted when drawing voting districts by population. Because a multitude of laws use the terms “person” or “people,” there would be no shortage of unintended consequences.”

It is a certainty that there would be consequences to such legislation, but what is interesting is that all of the parties involved in the debate skirt the fundamental issue: what do we mean by personhood anyway?

It is fairly simple to arrive at a reasonable conclusion over what constitutes the production of a new life form. When an egg is fertilized, being transformed from having a nucleus of single-stranded DNA to one with double-stranded DNA and thereby has full potentiality for developing into a complete human being, it is alive.

But personhood?  That is a rather more slippery issue. Can neurobiology tell us anything about personhood?

Martha Farah and Andrea Heberlein addressed this issue a few years ago in their paper “Personhood and Neuroscience: Naturalizing or Nihilating?”  They attempt to naturalize the issue, and suggest that not that a certain degree of neural development defines a person, but rather that we may have a network in our brains that recognizes persons – that we naturally arrive at conclusions about personhood when confronted with a person who is obviously a person. They astutely point out that if the personhood network exists (a conclusion that is hardly a certainty), it “is an adaptation to an earlier world, which contained fewer ambiguous cases of personhood. Sonograms did not show us our fetuses; people did not live long enough to develop Alzheimer’s disease, and vegetative states were fatal.” This leads them to conclude that:

(P)ersonhood is a kind of illusion. Like visual illusions, it is the result of brain mechanisms that represent the world nonveridically under certain circumstances.

They go on to suggest that:

The result of this analysis could be considered nihilistic. It does undercut ethical systems based on personhood, and in particular suggests that difficult ethical issues should not be approached with the strategy of determining whether or not the parties involved are persons. If personhood is not really in the world, then there is no fact of the matter concerning the status of a given being as a person or not, and there is no point to the philosophical or bioethical program of seeking objective criteria for personhood more generally because there are none.

In a thoughtful commentary on their target article, Adina Roskies clarifies the issue by pointing out that:

(W)hat they mean to say, is that sometimes our intuitive judgments that something is or is not a person are mistaken; furthermore, our inclination to persist in our judgments about persons in the face of evidence to the contrary prompts us to call those judgments the effect of illusion rather than simply errors.

Moreover, I like how Adina interprets their argument:

(W)hat Farah and Heberlein’s (2007) analysis suggests to me is that we can become better judges of personhood by paying attention to the things that matter, which seem to be the more abstract criteria the first system is sensitive to. And while the things that matter may still be up for debate, continuing the debate may lead us to develop a richer notion of personhood, one that admits of degrees and kinds. That alone strikes me as a huge step forward. Furthermore, rather than unquestioningly accepting the deliverances of our biological systems for person-detection in our everyday life, knowing that one part of our biological system for identifying persons is automatically entrained and subject to error should make us more cognizant of its operation and more skeptical of its output as we engage in the countless moral decisions we make each day.

What I particularly find appealing about these papers are the myriad ways in which they remind us to bring a degree of humility to the issue. Given the consequences of improperly defining personhood, checking our hubris at the door is probably a good idea.

But did they learn?  Apparently not.

In today’s New York Times, Martin Lindstrom has a high-profile op-ed piece in which he concludes that the relationship between individuals and their iPhones is more like love than it is like addiction. The conclusion may or may not be true, but the methods he uses to arrive at that conclusion – fMRI experiments with 8 men and 8 women, conducted by a neuromarketing firm – are no more robust or thoughtfully examined than the above-cited Iacobini et al. flim-flam that the New York Times previously published on politics. Mr. Lindstrom, who touts himself as both consumer advocate and branding guru but appears to have no academic credentials to warrant his interpretations of fMRI experiments.

Is nobody home at the New York Times?

Update: Tal Yarkoni has a detailed and thoughtful critique up about the Lindstrom article

The New Scientist

But if we unpack this a bit, we find that there are deeper levels of significance, and at least one of these are is worthy of further discussion.

Regulatory authorities such as the FDA have as their mandate to insure that products are both safe and effective. Let’s assume for a moment that the cognitive training game brought before the FDA is effective (evaluating this sort of claim should be fairly straightforward). However, if a particular cognitive training game is effective, by definition, it has changed the brain in some way; there is simply no other way that it could be effective (or at least none that I can think of). While everyone hopes for improvements in cognitive function with these games, there is no guarantee that the resultant changes will all be benign, or put more correctly, that they will be benign in everyone who tries the games. This lurking safety issue has been discussed, at least in passing, at the Sharp Brains Summit both this past year and the year before, and now will rise to the level of at least discussion with the FDA, if not actual guidance on the kinds of safety assessments that they would ask for before considering a submission.

But if one continues to pursue this line of thinking a bit, one is led inexorably to a nettlesome conclusion that I have harped on more than once: everything that we do, from reading a book to walking the dog to eating an apple, changes the brain in some way. I have discussed it most pointedly when raising concerns about the effects of repeated multitasking on our ability to pay attention, but the truth is that our brains are constantly inundated with information that causes them to change. Sometimes for the better. Other times, maybe not so much.

It turns out that the public is at least minimally aware that cognitive training games may have side effects. In our research group, we are running experiments which utilize contrastive vignettes to examine attitudes towards cognitive enhancement, and for various reasons we wanted to compare how people perceived pharmacological versus non-pharmacological interventions. In order to insure that our vignettes had veracity, in a pilot experiment run on MTurk we included a description of a mild side-effect that arose with the drugs, and to balance matters, told survey respondents that the same side-effect was present in a matching vignette that described a software program. As part of our pilot experiment, we wanted to insure that people found the side-effect plausible, and so we asked them what they thought. Remarkably, people found it equally plausible that the software would have a side-effect as they found it when we told them there was no side-effect.

The public may be somewhat more neuroessentialist than we think.

Retribution, the dictionary tells us, is the dispensing of punishment for misdeeds. Derived from the Latin re tribuere, it literally means to pay back. We humans have strong retributive instincts, and it is often said that this behaviour arose as a product of our evolution as social beings: the threat of retribution enforces social norms, and was among the features that increased the likelihood of cooperation among members of society in the early years of human evolution. Given that cooperation confers significant adaptive advantages to the group, retributive norms flourished, and whether via genes or enculturation, the desire for retribution has been passed on to us.

The value of retributive impulses in the modern world is more difficult to discern. We humans are noted for having the ability to not only act in a manner that is instinctive, but also to reflect upon the propriety of our actions. Amongst philosophers, retribution is often contrasted with consequentialism, the notion that the response to a misdeed should produce the best result for society. Consequentialism is possible because the modern human brain is able to reason, and by so doing we are able to anticipate near, medium and long-term futures: we can decide whether the best response to a misdeed is retribution, education, or even doing nothing at all. At different times, different responses may be called for. What matters most to the consequentialist is not the payback but rather the outcome. The tension between retribution and consequentialism is a hot button issue in the field of neurolaw, where neuroessentialists argue that it is time to rethink the concept of punishment, while traditionalists suggest that deterrence remains the best way of organizing civil society.

The dilemma of whether to pursue retributive or consequentialist actions is relevant not just to individuals, but to nation states as well. Mutually assured destruction, the cold-war military policy with regard to nuclear weapons, is perhaps the best example of retribution as an effective deterrent. Including vanquished Germany in the Marshall Plan, whose objective was to rebuild Europe as a bulwark against Russia, was consequentalist, and it too was successful. Today of all days, it is appropriate to reflect upon nations pursuing retributivist and consequentialist policies.

Ten years ago, when four airplanes were converted from civilian transport into missiles, much of the world was justifiably horrified. The perpetrators were quite clear about their desire to draw the ‘far enemy’ into a quagmire, and, as it turns out, they succeeded. A coalition of forces, led by the U.S., attacked Afghanistan with overwhelming force. Many cheered, driven at least in part by the very retributive instincts described above. Fewer cautioned that there may be alternative ways to respond, that the consequences of invading Afghanistan, not to mention the related War on Terror, merit careful consideration.

With the passage of time, the ramifications of pursuing retribution as a response to the crimes of September 11th have become apparent. The perpetrators have been scattered, losing sanctuary in Afghanistan and hunted internationally; many have been killed, few have been brought to justice for their crimes. In this sense, the retributive impulse has been satisfied. But retribution is only part of the story. Negative consequences are legion; the top of my list is that civil liberties, the crowning achievement of the Enlightenment project, have been curtailed, and a society that thrived on the basis of the openness of its institutions has been transformed into one that is suspicious, frightened, and fractured as never before. Remarkably, these very concerns were voiced the day after the attacks when the editorial page of the New York Times cautioned:

Americans must rethink how to safeguard the country without bartering away the rights and privileges of the free society that we are defending. The temptation will be great in the days ahead to write draconian new laws that give law enforcement agencies — or even military forces — a right to undermine the civil liberties that shape the character of the United States. President Bush and Congress must carefully balance the need for heightened security with the need to protect the constitutional rights of Americans.

The paths that nations take in pursuing what they perceive as their interests are complex, and the last decade has been thornier than most. One outcome is that the political schism between left and the right is more acute today than at anytime in recent memory. It is hard not to conclude that at least part of the friction derives from diverging worldviews: some hold tightly to the sentiment that retribution is always right and proper, while others value reasoned consideration of consequences.

We live.

We evolve.

Slowly.

Hat tip to Roland Nadler for illuminating me on some of the finer points of the retribution-consequentialism debate.

Lest one think that this is all just idle speculation, one need only read a 2005 paper by Andrew B. Meadows, a US Air Force Major with the title Fatigue in Continuous and Sustained Airpower Operations: Review of Pharmacologic Countermeasures and Policy Recommendations.  The paper begins by reviewing the Tarnak Farms friendly fire incident:

“On the evening of 17 April 2002, two US F-16s were airborne near Kandahar, Afghanistan providing on-call support for coalition ground forces as part of Operation ENDURING FREEDOM. The two pilots, COFFEE 51 and COFFEE 52, had been flying for approximately six hours when they detected what they perceived to be surface-to-air fire off the right side of their formation. Subsequently, COFFEE 52 requested permission from the Airborne Warning and Control System (AWACS) aircraft to employ his 20mm cannon in response to the threat. After a series of radio communications between the F-16s and the AWACS, COFFEE 52 called “self-defense” in response to seeing several men gathered near an artillery piece and released a 500-pound laser guided bomb on the target. Two minutes and twenty seconds had elapsed from the request for 20mm cannon fire and release of the bomb. The bomb detonated three feet from the gathering of men, killing four and wounding eight. The men were Canadian – friendly forces conducting a training exercise in the area (Dumas 2002).”

Meadows goes on to tell us that not only did the incident strain relations between the US and Canada, but there ensued a debate about what, if any, disciplinary actions might be brought to bear against the pilots. One of the key issues which arose in the subsequent investigation was the use of pharmacological enhancers by the pilots.

“Specifically, both pilots ingested dextroamphetamine tablets during the flight in question, with COFFEE 52 taking his 10mg dose approximately two hours before releasing the weapon (Dumas 2002). The issue of US pilots taking psychologically active controlled substances to counteract the effects of fatigue quickly ignited a public debate, further fueled by one of the defense attorney’s assertion that the Air Force had pressured his client to take dextroamphetamine, which, he argues, may have impaired the pilot’s judgment (Simpson 2003).”

The Tarnak Farms friendly fire incident certainly raised interest on the part of the military in alternatives to amphetamines (known in military jargon as Go Pills), and as Meadows documents in careful detail, the availability of modafinil filled that gap quite nicely. Re-reading this article today convinced me that that Allenby and Sarewitz are correct – soldiers are the ones who are most likely to be using today’s enhancement technology – a field experiment for ‘being all that you can be”.

For a rather hyperbolic view of the issue, take a peek at this video from The Hungry Beast, a weekly TV show on the Australian TV network ABC.

As an aside to the discussion of enhancement, Meadows goes on to tell us that not only did the incident strain relations between the US and Canada, but there ensued a debate about what, if any, disciplinary actions might be brought to bear against the pilots.

“Specifically, both pilots ingested dextroamphetamine tablets during the flight in question, with COFFEE 52 taking his 10mg dose approximately two hours before releasing the weapon (Dumas 2002). The issue of US pilots taking psychologically active controlled substances to counteract the effects of fatigue quickly ignited a public debate, further fueled by one of the defense attorney’s assertion that the Air Force had pressured his client to take dextroamphetamine, which, he argues, may have impaired the pilot’s judgment (Simpson 2003).”

He then points out something that has always seemed a bit ambiguous to me. I had read somewhere (a news article?) that commanders were able to order their subordinates to use pharmacological agents in the battlefield, but Meadows says otherwise.

Medically related requisites before use of either Go Pill include informed consent and ground testing. The informed consent process consists of counseling between the aircrew member and the flight surgeon that includes an explanation of the risks and benefits associated with either dextroamphetamine or modafinil, with clarification and emphasis that the use of Go Pills is voluntary on the part of the aviator.

I find that reassuring, but a bit of sleuthing turned up a somewhat variant view. Writing in Virtual Mentor, the lawyer Lee Black recounts the story of mandatory anthrax vaccinations in the military beginning in the late 1990′s, and the concerns that soldiers had about side effects, ultimately resulting in a lawsuit Doe v Rumsfeld. He concludes by stating that

If a soldier refuses a mandated anthrax vaccination, he or she may be demoted, discharged, or even imprisoned for disobeying an order. In the military, there are valid arguments for providing certain treatments without consent, where either the health of the individual or of the whole is at stake. And while it is true that the armed forces are exempt from many rules that govern the conduct of private citizens, to require treatment known to have a relatively high incidence of side effects tests the limits of these arguments.

Of course, anthrax vaccination and Go Pills are quite different matters, and it is unclear to this observer whether consent is a reality of the soldier’s life. What is clear is that the issue is sticky, complicated, and ripe for ethical analysis.