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Thursday, September 12, 2002

Session 3: Enhancement 3: Happiness and Sadness: Depression and the Pharmacological Elevation of Mood

Peter D. Kramer, M.D., Ph.D.
Clinical Professor of Psychiatry & Human Behavior, Brown University

CHAIRMAN KASS: All right, the two sessions this afternoon are sessions on a particular case study under the general heading of our inquiry into what goes by the wrong name of "enhancement," defined for now as possibly non-therapeutic uses of biotechnical power to alter by direct intervention the, quote/unquote, "normal" workings of the human body and psyche, whether by drugs or genetic engineering or other manners.

Our interest in this stems from the fact that we sense that these uses of these powers may raise some of the weightiest questions of bioethics, touching on the ends and goals, on the nature and meaning of human flourishing, and, at bottom, questions of humanization, super-humanization, de-humanization, and the like.

It has been a rather neglected topic in public bioethics, and yet it is, some of us think, one of the deepest sources of the disquiet that people feel about these new capacities, represented in remarks about man playing God or "Brave New World" or post-human future.

While this topic is hard to get a hold of, especially if you look at it across the board, we have decided at least to have a go at it, because if not us, who? It has not yet been taken up by any of the previous councils. It has been a subject of interest in the bioethics literature. We do have the freedom and the opportunity to step back from some of the potboiler questions of the sort we just finished to have a look at this field as a whole and see if we can develop some useful means of talking about it.

Nevertheless, rather than go at this in the abstract, we have decided to proceed case by case and look at a series of areas where these kinds of questions might come up. Over the next several months we will be inviting people in who have worked in these various areas to tell us what the new powers can do, how they are now being used, what the reasonable and unreasonable uses might be, and what we might expect in the future.

We have in October already lined up people to come talk about pharmacological modifications of memory, both to enhance and to erase. We have Francis Collins coming in December to talk on the possible enhancement uses of new genetic technology. We have people coming to talk about Ritalin, and we are in the process of getting people to talk about work going on in the biology of aging, as well as in choosing sex of children.

So looking both at the genetic and the pharmacological end, we will over the next three months try to educate ourselves as to what is going on and what this might mean. In the course of doing that, staff will try to develop some of the analytical tools.

One of the great difficulties in this area is to learn how to talk about them, and especially when you are dealing with things like the so-called higher human functions, it's especially difficult. It is for that reason that we are really very fortunate to have with us this afternoon two people who not only know the science and the clinical practice, but who have given a lot of careful thought precisely to this question of: How do you really begin to talk about this topic?

We are delighted to welcome Dr. Peter Kramer, who is Clinical Professor of Psychiatry and Human Behavior at Brown University and the author of Listening to Prozac, and Dr. Carl Elliott, who is Professor in Philosophy and in Pediatrics as well as the Director of Graduate Study at the Center for Bioethics at the University of Minnesota and author of a forthcoming book, Better Than Well: American Medicine Meets the American Dream.

Welcome to both of you. We are delighted to have you here.

We will divide the sections up as scheduled with Dr. Kramer going first. Dr. Elliott will speak in the second half, but in the discussion of each other's papers we would like to invite both of you to feel full members of the panel and join in the discussion.


DR. KRAMER: I am honored by this invitation, not a little daunted to speak before such an accomplished group of people. I got a phone call from Dr. Kass only four or five weeks ago about whether I would come down here, and I thought it might be an advantage rather than a disadvantage to prepare quickly.

I am an academic only in a marginal sense. I do sometimes write academic papers. But it was a relief to know that I didn't have time to prepare a full paper with footnotes, and so on.

The call found me at a particular spot in my thinking about issues related to enhancement in depression. I had written about those in a book that came out in 1993, Listening to Prozac, which then led me into a number of subsequent discussions, including some hosted by Carl Elliott.

But really in the interim, in order not to be trapped by the success of that book, I had written two very different books, one about intimacy in couple relationships and the other most recent one, a novel, which is also a novel of social commentary.

So I had just come back to this issue. While I am going to be very comfortable reviewing with you some of the thoughts that I raised in Listening to Prozac, the overview of what has happened in the eight or ten years since is more in the nature of a work-in-progress. I hope you will allow me that, to have that sort of uncertain status.

I want, as regards to enhancement, to consider with you the case of depression or, rather, conditions that are not depression but resemble it and might respond to interventions developed to treat depression. For convenience, I am going to call those conditions, the ones that aren't illness, minor depression or melancholy, but I mean for those words to extend to very solid degrees of health, where people have complaints that relate to depression but no one would consider to be ailments.

I want almost to warn you off this topic; I think that minor depression is uniquely problematic among the indications for enhancement that you are likely to consider. We had mentioned ordinary muscle mass or ordinary forgetfulness, and certainly ordinary shortness has been considered for enhancement or ordinary states of declining sexual functioning.

I think that minor depression differs from these in a way which I will call a problem of value. That is to say that we can value minor depression, whereas I think no one is likely to value forgetfulness, or one is at least less likely to value forgetfulness than one is to value the traits that make up depression.

But before we turn to that special problem of value, I want to begin with a question of method. This is the topic that in Listening to Prozac I call "cosmetic psychopharmacology."

Now to step back half a second, that book is built around a sort of core vignette that involves what I call recursion. That is, a person who, say, had a legitimate medical problem, was depressed, or had a serious anxiety problem, is treated with a medication, gets better, comes off the medication, and comes back to the physician, say, months or years later and says, "I'm not depressed again. I don't have that legitimate medical indication for which I first came to you, but when I was on the medication I was a better parent" or "I negotiated better at work" or "I had some benefit," that is the kind of benefit that people do in fact claim to experience on medications. "Will you put me on the medication again?"

Later, in discussing this issue at some of these ethics and philosophy conferences, I extended this sort of thought experiment, which actually occurs in offices, to one where somebody was never ill at all. So that say a woman comes into the office and says, "I have all the characteristics of the melancholic temperament. I'm a little timid. I have low energy. I am easily derailed from my purposes. And I have an identical twin sister. We were raised in the same family, had very similar childhood experiences, and where we diverged is that she had an unfortunate love affair and fell into a deep depression, was put on medication, and not only recovered from the depression, but had these other benefits of appearing, feeling more sanguine and less melancholic. Would you put me on medication? Would you prescribe for me based on the likelihood that I might have a similar response to the one she had?"

Now in considering dilemmas of this sort, these dilemmas are answered often in terms of medication side effects or long-term effects of medication. There's a general belief as regards mood that what goes up must come down.

One of my teachers, who was also a mentor of Dr. Krauthammer, labeled this sort of belief "pharmacological Calvinism" or "Puritanism." It may actually be that the opposite is the case, that depression is so damaging an ailment that what goes down goes down, and that intervening quickly allows, raising the level of mood, allows for future good mood.

But, in any case, there is general resistance to medication under the belief that it will incur some kind of doom and is morally weak or wrong in any case. To me, those are interesting considerations. Certainly, if you think about enhancement, you will have to think about those concerns, but they beg the question of the inherent morality of enhancement.

To that end, I framed this definition of "cosmetic psychopharmacology" that is also a sort of thought experiment. I defined "cosmesis" as using medication to take a person from one normal state to another equally normal state that is more desired or better socially rewarded.

I stipulated that the imagined medication is not addictive and not even directly hedonic; that is, taking the medication is not enjoyable, though the results of medication may allow a person better to enjoy ordinary pleasures in the manner that other normal people already enjoy them, and that the medication has no side effects or only such ones as a rational person would accept in exchange for the expected benefit.

I wanted to ask, in that case, what are the moral issues attendant on offering the medication? I think the same considerations would inform a discussion of electronic interventions or genetic interventions, although this is cosmetic psychopharmacology because I began with the example of Prozac, which is a medication.

I wanted, through this definition, through this term, to eliminate most frivolous uses of medication. So, in other words, this is not people that want to get high or to enter a radically-altered state of consciousness, and to eliminate concerns of safety, matters where we would say the doctor knows best, and even some issues of evolutionary fitness or unfitness by the constraint of changing from normal to normal, so both conditions have passed the test of generations, and to clear the field for the very issue at the core of your current considerations: What are the most basic moral considerations attendant on enhancement?

Now I didn't frame this issue in a vacuum, but the inspiration was, frankly and openly, the introduction of the first selective serotonin reuptake inhibitor, or SSRI, in this country, Prozac. Patients reported on that medication that they felt better than they had ever before felt, that is, better than before they had taken the medication at all, perhaps better than before they had fallen ill. They use this expression that Carl adopted for his book, Better Than Well, which I take to be the same as this term "enhancement."

The manner of this improvement was different in different instances, but a shorthand description for what patients reported was that medication for them was like Garrison Keillor's powder milk biscuits, that the SSRIs lent them courage. They made patients less sensitive to rejection or loss. They occasionally lent them energy, allowed for greater optimism and social assertiveness.

In those patients who had suffered psychic injuries early in life, it seemed that they were more the way they had imagined they might be before the injury occurred. To use a political term, the medication was empowering, but it was worrisome on a different level because it was empowering in precisely the direction that the culture values.

The medication could be called conformity-inducing as regards a favored personality style for the modern woman, in particular, although that style includes a measure of assertiveness and potential for rebellion. That is, it was a model of the way we want them, a modern woman might be when she was admirable, but wasn't conformity-inducing in the sense that her behavior, her choices, would then be conformist or subject to influence.

This change was in response to a medication which, whatever its substantial negatives, had a side effect profile that was more acceptable than that of medications that had come before. Most patients didn't feel drugged or aware that they were on medication.

In Listening to Prozac, I detailed the reasons I had for suspecting that such effects might occur, that is, to give credence to these reports. In brief, at the first level the SSRIs worked through serotonergic pathways in the brain, and in other mammalian species serotonergic pathways appear critical not so much in the maintenance of mood as in the regulation of status hierarchy.

Again to simplify, alpha males have high serotonin levels, and in times of turmoil within the troop, animals premedicated with SSRIs are more likely to assume dominance. This is a very antique mechanism. If you look at lobsters that are closer to the food supply, apparently, they have a better serotonergic transmission than lobsters not near the food supply.

It seems to be both from clinical observations and from pre-clinical research literature that SSRIs' major effect might be in inducing an overall sensation of social well-being. As you know, some of these medications subsequently have gotten indications for the treatment of social phobia.

Whether it is true that in humans these medications have the effects I have suggested is a question that has never been properly tested, but there is one detailed study that appeared in 1998 that did find that normal people given Paxil were more socially adept when confronting a test challenge. They were given a very-difficult-to-solve problem, put in pairs, and the observers saw who was the leader in the pair and how they got help in solving sort of a tangram problem. Academic articles citing the experiment said that the effects that this experiment found were the ones that I had predicted.

Although we can imagine quite varied instances of cosmetic psychopharmacology, the test case I considered was this one that had to do with a movement along the personality spectrum from self-doubt to a sense of belonging or insider status or from melancholy to sanguinity.

I knew that observers might be troubled by such use of medication, and the question was, why? In fact, I was troubled by it. Was this expectable response psychopharmacologic Puritanism or Calvinism or did it have some inherent moral justification?

In considering this question, I began with the observation that for many years we have had an intervention that meets all but one of these standards of cosmetic psychopharmacology, and that intervention is psychotherapy. The standard that it fails to meet is that it is not a medication, although some recent research does suggest that in gross terms psychotherapy may work through brain mechanisms similar to those of pharmacotherapy.

That is, there are these studies looking at complicated brain imaging of people who have had either psychotherapy or medication, and after a few doses of each, the changes in the brain in people who successfully respond look similar.

We have no objection to a physician's conducting that intervention, that is, to giving psychotherapy for making a melancholic person, say, more sanguine. Indeed, part of what seems eery or uncanny about the new medications is that they resemble psychotherapy. This is so both as regards psychotherapy's ends and its processes or intervening effects. That is, patients in studies report that antidepressants can connect memory to affect or make painful memories more bearable or accessible, and so forth.

To make the ethical case against medication yet tougher to prosecute, I should remind you that there are psychotherapies that work through mechanisms other than insider memory. There's been no ethical debate attaching to support of psychotherapies where the therapist helps the patient to bear affect or tolerate stress without relying on the transmission of understanding, and it has been only the most minor ethical debate about paradoxical therapies intended to catapult patients into more desired states through means whose intent is kept hidden from the patient entirely.

That is to say, we have lived comfortably for 50 or 100 years with the goal of enhancement within the medical profession. In truth, we might say that, as a society, we have lived with this goal much longer if we accept that people have tried to make themselves less melancholy through a variety of means that in Listening to Prozac I call "quest," methods such as religion, friendship, work, self-inquiry, and so forth.

An interesting book for the Council to look at is Martha Nussbaum's "Therapy of Desire," which frames the schools of Hellenistic philosophy, the Stoics and Cynics and Epicureans and Aristotelians, in terms of their efforts to create relative invulnerability to the pain of loss. In this sense, enhancement is at the base of the Western cultural enterprise.

By this analysis, the new issues as regards psychopharmacology will ignore the questions of ends altogether and will cluster around means. Although in sentiment Listening to Prozac was on the side of those who feel unease at these potential new uses of medication, the challenge it set was to specify the cause of that unease on the basis of differences between the new technology and the old.

I would venture to recommend this method to the Council in general when framing its response to the challenges of enhancement. In a given instant, is it the goal of enhancement that raises ethical challenges or the means? I think the method behind cosmetic psychopharmacology as a thought experiment is a useful probe in this clarification.

For any given proposed enhancement, if there were a purely harmless means of achieving it, would the ends still be ethically troubling? If not, we're down to the issue of risk and benefit, broadly taken, which is a manageable topic.

If I can be allowed a parenthetical digression on the risk-benefit question, the automatic assumption might be that we would require a lower ratio of risk-to-benefit for enhancement than for treatment. We hesitate to put the healthy at any risk, and the ill are already at risk. For them, the question is not whether to play the game, but how. The paper you read this morning made some remarks in that direction, that ill people are in some ways more suitable for taking on certain risks.

But if we add in the element of judgment, our perspective may change. After all, if risk and benefit are properly calculated, those terms of the equation include the differing starting points of the players. What the equation lacks is an assessment of an element we might call freedom or coercion or leisure.

The healthy actor is fully able to make an unpressured judgment. His vantage begins with a self as it is ordinarily. His decision is truly his own. On this basis, he might ask to be permitted to assume a greater level of risk than he would demand were he ill.

The example of depression is illustrative. Who has the less impaired judgment in terms of informed consent, the person when he is free of depression or the person who is merited or diagnosed because of impaired memory and concentration, suicidality, low self-esteem, and the like.

To be sure, there are meta-considerations beyond the perspective of the individual seeking enhancement or even a physician supervising the intervention. I mean effects on the culture and effects mediated by culture.

One difference between medication and psychotherapy might be their differing effects on the social atmosphere. For example, if harmless medications were available that could reliably make people more assertive, then social coercion might come into play. A boss might say to a salesman, "Don't come back until your medication level is adequate," or words to that effect.

In such an atmosphere or such a workplace, those who are not characteristically assertive off medication would be at a disadvantage relative to those on. The analogy to steroids in sports is evident.

This coercion might apply all the more for medications less benign than those imagined by the strictures of the thought experiment I have labeled cosmetic psychopharmacology, say addictive medications or those with insidious harmful effects. We might fear medications because of the influences of their manufacturers, the pharmaceutical houses.

It does seem that the risks for distortions in informed consent differ as between medication and psychotherapy. As regards decisionmaking, the pressures brought to bear by therapists would tend to be more intimate but less organized and less global.

Regarding considerations of evolutionary psychology, I have said the ground rules of our thought experiment, normal to normal, make certain concerns disappear. True, melancholic traits may have conferred fitness in the hunter/gatherer environment, but then so did sanguine ones. At the level of the individual nothing is lost, but at the level of the culture we might fear the effects of too much uniformity, everyone a top banana.

The same worry could conceivably result from psychotherapy or religion, but our experience is that quest has never so far worked in this overly-effective way. This is the challenge I posed with cosmetic pharmacology as a variant of enhancement.

I would like in our remaining time to update you on my thoughts of the following eight or ten years and to say something about progress and prospects for progress in biological psychiatry.

This may be going on too long. Are we comfortable?

The first set of thoughts have to do with my own experience. You will recall that I had made a division between ends and means, saying that since we accept ends of enhancement when quite mechanical forms of psychotherapy are applied, the principal issues must be those attached to the new technology.

But something strange happened. When medical ethicists took up the challenge, for the most part they continued to talk about ends. You will hear from Carl Elliott, and may have seen his work referenced in my monograph and his own in the Hastings Center Report in your materials. I don't intend today to address that material in detail, as I do in my own written reply. But I can say that Dr. Elliott makes a series of cases for alienation as a valuable human trait.

But by way of precis, let me propose a quick thought experiment. A patient in one of the recursive vignettes returns and says, "I'm not depressed again, but I noticed on the medication I felt more comfortable in conventional social groups. I had less sense that I was an outsider. People found me less awkward. I was less troubled by absurdities and contradictions. I was less finicky. And I have been proposed for membership in a conventional business leadership group. Acceptance would help my career. For the probationary period, I would like to resume taking the medication."

If this request sounds unlikely, I should remind you of that study by Knutson and Wolkowitz in 1998 demonstrating that an increased ease in affiliative behavior and leadership behavior in response to serotonergic medication. I take this request as invoking the sort of possible objections made by Dr. Elliott when he writes memorably that, "To address alienation as a psychiatric issue is like treating Holy Communion as a dietary issue. It's a category mistake."

I think that the question of alienation is an open one. Alienation is very much an element in some psychiatric conditions, and even where it is not, it might legitimately engage the psychiatric enterprise and all of its aspects, including the pharmacological.

But at the same time, I want to say that the recursive vignette is an example of a request for enhancement, not a treatment of an illness, and it does raise questions of value, in this case the value of alienation, which is a trait philosophers have valued on a variety of grounds, for example, placing it at the core of existentialism.

I should add that, in the wake of Listening to Prozac, ethicists have written in praise of rejection sensitivity and self-doubt. However painful, these traits are aspects of self-awareness and awareness of circumstance. Value can be attached to almost any of the personality traits that are also symptoms of depression.

And there are other problems here. I saw this article by Stephen Braun also in the advance material, where he talks about having these mini-storms in his life where he would feel depressed for a short while, maybe not rising to the level of illness, and wondered whether there was something behind them, although apparently there was not, whether there was some problem in the marriage, or so on.

Of course, psychoanalysis has taught us not to trust our own testimony. So it might be that someone would think something is random, where some adequate explanation or adequate inquiry would show that there was some particular human value in having that symptom. He concludes in that article that there is not, that this is just some kind of mental glitch, and is happier being on medication.

This circumstance makes depression and its neighboring conditions special, if not unique, among the examples you are likely to consider. I think I have said this.

I have come to think that the matter is yet more difficult, that ethicists might value depression itself, not just the neighboring conditions, call it illness though we may. One provocative test of this assertion is this question: Would we want to eradicate depression the way we eradicated smallpox, so that no human being experiences depression ever again? This question might elicit different answers, presumably a wider range of answers than a comparable question asked of cancer or diabetes or arthritis or some other illness.

Now think of the objection to this provocative test. It displays and conceals verbal ambiguity packed into the word "depression." That is to say, some people might be content to eradicate or entirely prevent the severe condition depression if its boundaries could be well-demarcated.

It is the minor conditions that make the question sound troubling, but that objection is a demonstration of the problem of value of minor depression. That is, the reason people make that objection is that, while they are quite happy to get rid of major depression, even those who are, they want to hold onto minor depression. That is why they think it is a trick question. I hope that was clear. If not, we can forget about it or discuss it.

I mention this possible exercise as a quick proxy for a longer discussion of the premise that, when it comes to minor depression as regards enhancement, some possible objection attaches to the goal.

In recent years I have come to think that the argument from psychotherapy deals with these concerns too easily because of unspoken beliefs about the test intervention. Ethicists seem to think that psychotherapy does not work or does not work thoroughly or acts only through a limited sort of means, such as insight. It is only in the face of interventions we imagine to be ruthlessly effective, such as medication, that the issue of value emerges.

I want to mention a second issue that makes depression special, although not unique, which is that it is a true spectrum disorder. Your materials also list how psychiatrists diagnose depression. It is based on having a depressive episode, and to have an episode you think about nine symptoms. You need to have five of these symptoms continuously for 14 days and they have to rise to an adequate level of severity, and if so, you have a depressive episode, and then from there you might have different kinds of depression.

This is the sort of sharp-edged definition that allows for enhancement paradoxes. Shortly after the publication of Listening to Prozac, when colleagues challenged the assertion that SSRIs could affect people who had never been depressed, and I mounted variants of the identical twin challenge proposed earlier, if the, quote, "unafflicted" twin had only experienced four symptoms, would she, nevertheless, respond to treatment?

A similar question might serve to indicate the difficulty of defining enhancement. If a person has never suffered more than four symptoms, but those four are chronic and disabling, does addressing them constitute enhancement or treatment? What of those who have experienced only three symptoms? Will a single symptom suffice? Is this sufficient?

In reality, in a doctor's office people do come in with just one symptom. You know, they are only suicidal, say, or they only have low self-esteem. We are often happy to treat those.

These questions are made more complicated because of the results of recent research. It turns out that the accepted definition is arbitrary on every axis: the number of symptoms, the duration, and the severity. In other words, if you looked at people with only four symptoms or have five symptoms for ten days or, you know, have a lower level of severity of symptoms, they all have a degree of risk for future bad outcomes that is very similar to those who meet the definition. This is a true spectrum.

The same is true if you try to raise the bar, that is, if you try to look at really core symptoms of depression like suicidality, you know, you start losing some people whom everyone would say are truly depressed and you still include people who turn out to do very well in the future.

In fact, only half of people who meet the initial definition of depression ever have another depressive episode. I think psychiatry is much more interested in this term of illness, in this sort of career of depression over a lifetime.

This doesn't make the definition of depression a bad one. It has proved very useful for research and public policy purposes, but it limits its applicability to ethical conundrums. Clearly, we would not consider a culture immoral that had a differing definition of depression, slightly above or below ours in terms of the severity demanded.

The matter is all the more problematic because of recent research that emphasizes the physical deterioration implicit in depression. There are studies that show brain nuclei to be atrophied or perhaps small in the first place in patients who have been depressed, and the size, the loss of tissue appears to be correlated with the length, lifetime length of depression, the number of days of depression. There are also post-mortem studies that show cellular disorganization, glial cell atrophy. So this looks like a condition that doctors legitimately might want to prevent on the basis of anatomical findings.

In addition, there is research on what is called sub-syndromal symptomatic depression that looks as if it leads to all sorts of bad outcomes, like worse results in heart disease, and so on.

The result is that many of the areas that ten years ago we would have thought about as the realm of enhancement have probably been subsumed into the medical enterprise. I warned about this tendency under a phrase I called "diagnostic bracket creep," the tendency of diagnosis to expand to meet the medication available.

Although that designation contains a measure of sarcasm, the movement is not necessarily for the worse. What happens is, if you have an effective medication, you start doing research on ever more minor conditions, and you may find legitimately that they are as fully medical under the concerns you had as the ones you had started treating when you needed a more uniform population to do your research.

So I have proposed two sets of problems: Do we grant legitimacy to the concern over enhancement based on valuation of the target ailment, or lack of ailment, and can we define a territory that is outside the legitimate medical enterprise? It would be interesting to see what would happen if worlds collide.

Imagine an ethical determination, say by a commission such as this one, that the culture values a trait related to depression and considers its diminution to be problematic unless certain conditions are fulfilled. So say we value alienation and say really medication ought not to be used to treat alienation.

Then imagine that research defines a cause and set of biological markers of a subtype of depression, and that subtype turns out to include some of the cases where we have said it is morally preferable for people to live with the trait. Could we stand fast against the suasion of biological evidence?

The same argument might apply to prevention. To create an extreme example, say that depression in offspring is caused by maternal exposure to a pathogen. So say it is like toxoplasmosis, where if the pregnant woman is exposed to feces of cats carrying toxoplasmosis, the child is at risk in life for certain ailments.

And let us say that if you didn't handle cats, your child is much less likely to be depressed. Would you sincerely — would you take seriously the worry that your child also might not be alienated? That is, do we so value these traits that, if they thoroughly entered the medical enterprise, we would continue to value them, and someone would say, "No, women ought to go on handling cats because otherwise the human race would lose this valuable problem of melancholy"?

One response is that we don't think depression or melancholy personality are like that, but of course there have been surprises in medicine before. Well, what do we think depression is like?

There are a number of speculative models now, some of them built on a neurobiological analog of what we see in the behavioral phenotype; namely, problems and resilience. In other words, that the brain in depressed people does not produce reparative chemicals. So that when there is stress, whatever damage is done remains more in the brains of depressive people than other people.

A fuller model, worked out in rodents, involves stress, increases in stress hormones in the brain and then difficult-to-reverse brain damage. A yet fuller model sees depression as maybe 35 or 40 percent based on genetic vulnerability, where that vulnerability merely takes you further down that road of the results, the effects on the brain of repeated stresses.

And a yet fuller model sees subtypes that may be tied to particular stressors, such as, for example, declines in vascular sufficiency. If this is so, and I know that was a quick runthrough but just accept perhaps this conclusion, then prevention may be a better strategy than treatment for depression.

Now no one objects to prevention for depression. There are all sorts of interventions with high-risk mothers, say, to prevent depression in children. But, again, this may be a false counter-example because it seems so natural and because it is not thorough.

I haven't spoken to you about developments in psychopharmacology, and the reason I haven't done that is that I don't think there have been ones that present dramatic new ethical problems beyond those that I talked about ten years ago in terms of what has come to market.

But there have been medications that haven't come to market because they have had side effects on the liver, and so on, that involve interrupting the effect of stress on the brain. These include CRF inhibitors intended to block receptors for corticotropin-releasing factor. In lower mammals these compounds prevent even the effects of prenatal stress on offspring. So that you can imagine someone undergoing a stress, taking these medicines, and not suffering the deleterious anatomical presumed effects of stress on the brain. These do, I think, present new ethical problems.

For instance, if a child lost his or her parent, lost a mother, would you want to give such a medication to prevent the future liability for depression, and if you did so, would you feel that you were preventing certain normal responses to the loss of a parent, such as development of, say, melancholic personality traits? Or taking away this kind of proxy problem that children present, would you want a spouse to take it upon the death of a pre-deceasing spouse?

And at the next level of science fiction we can consider genetic interventions. Robert Sapolsky and colleagues have done lower animal experiments in terms of introducing genetic material to prevent cascades of stress hormones that follow upon strokes, so strokes don't generalize. So that if an animal has a stroke, it won't have the permanent elaborator effects of that stroke on the brain.

Sapolsky has talked about the possibility that one could in theory create genetic interventions that would have the same effect as regards depression. That is to say, when a person who is liable to become depressed in response to stress would have such an intervention, that person would then be less liable. Are we concerned that such interventions also would prevent alienation, moodiness, sensitivity, and the like?

This forecast, which is also in the way of a thought experiment, raises questions about agency. Ought we to allow or encourage mood enhancement, perhaps under the name of resilience, as a boon to public health or economic productivity, or would you prohibit or discourage or attempt to minimize enhancement, perhaps even when it occurs as a side effect of clearly legitimate or mainstream medical projects? Is depression a special case? Ought it to be a special case?

Our own current interest is in a topic, my own current interest is in a topic, I'm sorry, that bears directly on this last question. What is the origin of this sentiment for minor depressive symptoms? Is a "faute de mieux" a result of millennia where men and women could not prevent these traits and so had to live with them, or did the human race develop strengths out of handicaps, so that we entail some risk, individual or societal, when we mitigate melancholy?

I am, frankly, suspicious of much of the sentiment in favor of melancholy. If we accept the medical model of depression, then we may imagine that some years hence that sentiment will resemble the romanticization of tuberculosis in the 19th century. Although the role of depression in the culture is yet more substantial, it informs our very notion of romance and has for centuries. If that is confusing, I can say more about that as well.

I want to end, as psychiatrists often do, by showing the other side of the coin. I have said that depression and its lesser relations may be an unfavorable area to tackle because of the unique medical and cultural qualities of the core disease and the sentiment or valuation attaching to associated traits.

But I might also want to say the opposite, that these questions are timely. It seems to me important to say what we want to say about melancholy now before we are unduly influenced by the facts. The valuation, say, of alienation is a cultural question and best assessed at the end of millennia in which it gains its status, millennia during which its causation remained unclear. Once we know more about the causes of depression, this debate will be that much harder to engage, so prone are we to give biological dissections priority.

I see that I have taken an odd tact in outlining issues arising from concerns about enhancement. In the end, any wider opinion you issue will focus on informed consent, implicit coercion, social conformity, the natural and unnatural, risks of addiction or other forms of seduction, modes of balancing risk and benefit, and the like.

My only justification for the path I have taken is to say that it is my interest, the one that has captured my interest, and that it serves to underscore the question that I think should come first in considering enhancement, since it properly informs all the others, questions of value.

So why don't I stop there? I am happy, you know, in the course of the discussion to say more about my own opinions on this issue, whether if we discovered tomorrow that a combination of vitamins actually prevented minor depressive traits, people ought to be encouraged to take those vitamins or not, but I think I should hear from you first. Thank you.

CHAIRMAN KASS: Thank you very, very much for a very rich and stimulating presentation.

Let me just open the floor for discussion and hold my own comments. Gil?

PROF. MEILAENDER: This is very interesting and very puzzling. I would like to get you to think a little bit for me not just about kind of reporting on what people think, but react yourself with respect to one of the kinds of issues you raised especially near the end.

I mean, we often think, I often think at least, that to love anyone is to make yourself vulnerable because you might be hurt if the person is lost. I would like to think about your case of the person being widowed, say. What would be an appropriate reaction to losing the person to whom you had been married for 25 years, say, or something like that? I want you just to reflect normatively on it for me now.

If I lost my wife after 25 years, and it wasn't that I just soldiered on kind of, you know, because there were things that had to be done, but I just carried on kind of happily, readjusted, and so forth, and seemed positively buoyant, in fact, on many occasions, would you judge there to be — I mean, am I defective as a human being in some way? Has something gone wrong? Or if not, then maybe it would be desirable for you to help anybody who lost his or her spouse after 25 years to just carry on buoyantly.

Just think about the case a little bit more for me. I am really interested in what you, yourself, want to think normatively about it.

DR. KRAMER: I am very much within the culture. So my answer is likely to be an answer from within the culture, and I certainly would think you had missed some of the richness of life if you didn't mourn or grieve to some extent.

But that is more one vote.

PROF. MEILAENDER: Are there different cultures on that matter?

DR. KRAMER: Yes. Yes, there are. One of the things I wrote about in Listening to Prozac was a particular case that was initially admired of mourning in rural Greece. In rural Greece I guess women wear black after the death of a pre-deceasing child or husband, and they are given a long period of mourning during which they are very much supported by the rest of the community and allowed not to do certain tasks that ordinarily a woman would be required to do, and so on. And this was held up as sort of a model for the mourning process.

But someone who looked more closely at that culture found that some women were very antsy and grumpy about this, that they recovered much faster than this ideal period required, and that they were just too resilient for that culture. It didn't fit them well.

I think there is a range of naturalistic responses to loss. But my question is more for the philosophers, which is, forgetting what I think is natural or normal, where does the value attach? In other words, do we more admire the women who take a year or the women who after a couple of months want to be back at work?

And is the value in thinking about the person constantly or being forced to think about the person constantly? That is, let's say you could take a medicine that after a couple of months would relieve you in some way. You certainly could go on thinking about your lost loved one as much as you wanted, but you wouldn't be forced to.

So I think ordinarily when we think about morality, something is more admirable when it is done without coercion than when it is done merely because there is no other choice. So I think it is an interesting question.

More broadly, I want to say something about suffering because I think we value suffering altogether. The question is, do we value suffering because we learn from it and it is morally somehow enhancing — that's probably the wrong word — or do we value it almost because we can't avoid it in this manner that I called "faute de mieux"?

I had an interesting — I am just going to tell a story, which is I was in Denmark, and through various storms and things I was forced not to go where I wanted to go and ended up at Isak Dinesen's house, Rungstadlund, with a Danish pharmacologist. We had been talking about these sorts of issues that we are talking about today, about the amelioration of depression.

People always say, what if Prozac had been available in van Gogh's time or in Denmark what if Prozac had been available in Kierkegaard's time? So I said jokingly, "What if penicillin had been available in Isak Dinesen's time?" because the story on Dinesen was that she suffered from syphilis given to her by her Baron Bror Blixen, the bad husband in this movie "Out of Africa". And the chronic pain that she had from the syphilis made her a darker writer, and so on.

And no one objects to treating syphilis. There is no moral objection or richness of human experience objection to treating syphilis in a woman infected by a feckless husband. I mean it is just not something we consider at all.

This pharmacologist said to me, "You know, she probably did not have late-stage syphilis. Probably she was cured of the syphilis early by arsenicals. There was no trace of this ailment in her later life. She was on phenothiazines and barbiturates, and probably what she had was depression."

So why is there a Prozac question and not a penicillin question? Just as an interesting — this is not, I know, it doesn't have to do with mourning in particular, but why is it that we ask questions? And I think the answer to that question, in my mind, having thought about it, is that depression is sort of a proxy for suffering altogether, whereas these other illnesses are all individual forms of suffering. What we don't want to lose is something that relates to the capacity to suffer, although any given instance of suffering we would be happy to free the human race of.

I know that was not a good answer to the question, but —

PROF. MEILAENDER: Just a brief followup: I mean your distinction between any given instance of suffering and the capacity is a good one. I was just going to say, I'm not particularly big on suffering, but let me try to put the question, or at least a version of the question, once more in a way that doesn't make it a question about medicating at all.

I don't know how you would get this information. It would be a difficult question. But if you were to die and then you were to find out that your wife, having given you a dignified burial, just carried on, you know, we're not talking about five years or anything, just carried on —

DR. KRAMER: I got the question.


PROF. MEILAENDER: — didn't seem to matter at all, and you somehow could get this information and evaluate it, would you think yourself to have been loved?

DR. KRAMER: Yes. Well, you know, an interesting question is, was I loved? You know, that is, I think that you are asking the question that anybody — I mean it is the right question. This is the right first question.

On the other hand, imagine a science fiction future in which someone looks back and says, "Do you remember primitive days when attachment was guaranteed by the pain that followed upon loss, whereas now we love because we love and we are free to love. We would be free to withdraw our love, but we love because we really love."

You know, it is like what parents say to adopted children, "I had you because I wanted to have you. We had you because we wanted to have you. We chose to have you."

So that one might say that a more noble form of love would be one that wasn't predicated on pain of loss, although, yes, that certainly would seem unnatural to us.

I mean, I suppose one reason it would seem unnatural to us is that we would have further beliefs about what the nature of that love was. The availability of a medication that erases those assumptions, that is, you assume a fully normal, loving person would have been able to abbreviate the mourning process through those, whereas today we would think that wasn't love at all, and we would be right.

CHAIRMAN KASS: Are you satisfied for now?

Michael Sandel, Mary Ann. There's going to be a queue here.

You've started us all up. Thank you.

PROF. SANDEL: Well, I found this very provocative and suggestive. Not having thought this through fully at all before hearing your talk, it strikes me that the issue or the thing that troubles us isn't the medication at all, but the mode of being that the medication induces or promotes. Let me say why what you said suggests that to me.

You identified certain traits or dispositions associated with cosmetic pharmacology, traits that people might want, even if they are not clinically depressed. Then you mentioned some other means of acquiring those traits, traits like optimism, social assertiveness, a sense of the sanguine, ways of acquiring those traits other than medication that we regard as acceptable or unproblematic: psychotherapy, even religion.

Your suggestion there, as I understood it, was, well, if we accept those ways of acquiring these traits, then why not accept the medication, too? By the way, I would add to the list of other means of acquiring those traits of optimism, social assertiveness, a kind of blithe optimism, and sense of being sanguine, maybe even a blithe vacancy — I would add to the drugs, the psychotherapy, and the religion spending too long in Southern California.


In fact, before I knew about Prozac or what traits it promoted, I was struck at a party once by a woman, a friend of my wife's, who seemed to be more than usual displaying these traits, and I wondered about that and then later learned that she was taking Prozac.

Now in reflecting on the traits, what struck me about them was I can understand why someone might want them rather than to be, say, fraught with self-doubt or something like that, and yet there is something associated with those traits, however desirable given the alternative, that seems shallow or a kind of vacancy, a kind of unreflective self-possession that goes with them.

I would say, having spent some years of my life in Southern California, that that's true of people there in general, even ones who aren't on Prozac. That's actually one of the reasons that I wasn't eager to go back or to raise a family in Southern California, and it had nothing to do with drugs.

But it did have to do with a certain way of being that I thought was promoted or made more likely or induced by living in Southern California that I didn't really want my kids to grow up having, nor would I really be happy if I found that they joined a religion, stoic or otherwise, that promoted those kinds of qualities, even though I would want them to be assertive in other kinds of ways.

But the package of dispositions that we are talking about here that seem to be associated with Prozac — and I don't know how uniformly that's the case — but it seems to me that to possess those traits too fully is to lack, never mind alienation and melancholy, maybe that overstates the alternative, but it is to lack a certain kind of depth of character or a quality of reflectiveness, even short of being plagued with kind of clinical melancholy, if there is such a thing.

Then when we consider that there are risks and side effects to acquiring this morally-dubious package of dispositions, then you really wonder about the character of someone who would aim at that mode of being, knowing that it carries certain risks. I mean it is bad enough just to come into the possession of that mix of traits with the superficiality and kind of vacancy that sometimes attends it, at least around the edges, but then —

CHAIRMAN KASS: Some of us "resemble" those remarks.


PROF. SANDEL: But then to actually undergo risks and side effects for the sake of that really might lead to further worries about the character of the person who would go in for it. So that makes me think that really the issue isn't enhancement, because here on reflection the making better the enhancement isn't really fully an enhancement.

After all, if you take this account of the package of dispositions — and so maybe we can accept all of the analogies that you propose and say that any of those means to this mode of being would be troubling and for the same sort of reasons, though the side effects might differ in the case of religion, psychotherapy.

In Southern California, the side effects might be more or less grave. It would depend, but the graver they are, the more we would worry, but in any case, we worry for the same kind of reason about all of them.

DR. KRAMER: I wish I had taken notes because I think there are about five issues, you know, in that, and I hope that this council doesn't end up forbidding people to move to Southern California.


DR. KRAMER: Because I think that is almost ?- let me tell you what —

CHAIRMAN KASS: We're only advisory.

DR. KRAMER: I am raising my children in New England for this same reason.

I think there are some problems. One has to do with what's in the package, and it does happen that almost any psychotropic medications we know about sometimes cause apathy, and almost any antidepressant we know about sometimes causes mania. So I think that part of my normal to normal requirement would meant to get rid of what very likely are side effects or negative effects of actual antidepressants in actual people with mood instability.

So that, you know, I think some of what one sees actually on antidepressants is apathy or silliness, disinhibition, and so on, and that I would want to exclude those cases. So it's not clear exactly what the package is.

But I think that the Southern California example, it troubles me, and I think it contains a judgment on a lot of normal people. That is, we admire and think to be intellectual people who have trouble making decisions or are, you know, very reflective, are prone toward pessimism and worry.

And the question is: to what extent are we just admiring ourselves and to what extent do we want to sign our name to that as a moral position.

I encountered this when I was asked to write a preface to a new edition of a book by Carl Rogers, the Midwestern American psychologist, who I knew largely through being considered not to be intellectual, and I thought very seriously about why he wasn't an intellectual, because he was someone who had written a number of research papers at a time when people in the mental health field rarely did, and had been innovative in certain research methodologies and was in dialogue with some of the great people of his era.

And I think the answer was that he was an optimist; that, you know, a Midwestern American optimist could not be an intellectual. And even though when his ideas were stolen by, you know, sort of Viennese depressives, they took on a different cast.

But that is the nature of my answer, which is I'm asking us to rethink this denigration of optimism on the assumption that it comes with blandness and so on.

The question you point to is exactly the question that troubles me, whether we're not too quick to value depressive traits exactly on those grounds, and you know, what do we make of Southern California? I think it's an interesting question.

PROF. SANDEL: Could I give just a quick reply? Which is I entirely agree that what I've said contains a judgment on normal people, but the whole tradition of moral philosophy and moral reflection consists precisely in that, containing and engaging in reflective judgments on normal people, including ourselves.

What is moral reflection if not precisely that?

DR. KRAMER: Let me actually make a second answer to that because I think there is another answer to it, which is to think about William James' first and second born religious joy. That is, some people just seem to be born, you know, able to believe in God and to believe that the world is good, and that we somehow consider those people less morally worthy than people who have to struggle and go through suffering and come to, you know, essentially what James claimed was essentially the same state of religious optimism.

You know, the moral enterprise, it is true, values troubled people more than untroubled people, but it's also true if you think about these Stoics and Cynics and Aristotelians that the apparent goal is to live a life less troubled by loss and pain or, you know, in the case of a religious person, to get to the state of faith.

And then the question is: why is it that just having it naturally or having it through some automatic means is less valuable than having it through some other means?

I mean, I think there would be an answer along those lines, as well.

CHAIRMAN KASS: I have Mary Ann and then Rebecca and then Paul.

PROF. GLENDON: Well, first of all, thank you for such an interesting paper and discussion. There's so many things one would like to ask.

I'm going to start with some little questions that a number of us were wondering about this morning and then come back to this discussion between you and Michael Sandel.

In something we read it was said that Prozac is the fourth most commonly prescribed drug in the United States in the year 2000. Would that be approximately right?

DR. KRAMER: I don't know the answer to that, but let's say it is.

PROF. GLENDON: Okay, and so one thing we were wondering about about the top three, would any of those be psychopharmacological?

DR. KRAMER: My memory is that the top ones, you know — that the top one or two always have to do with high blood pressure and esophageal reflux, but certainly if you throw together Prozac and Zoloft and so on you get pretty high up on the list.

PROF. GLENDON: So this is the last of the little questions. Would you want to take a stab at guessing what proportion of the American population at any given time is on some kind of mood altering drug?

DR. KRAMER: I don't know the answer to that, and someone does know the answer to that. I just don't know.

But you know, an implicit question behind this is: how does the prescribing relate to the burden of illness? And the data I've read is that you could still double the number of antidepressants, maybe more than double before you would reach the number of people who at any one moment are thought to be depressed by those criteria that I mentioned.

Now, we could discuss whether those criteria really include some things that aren't depression, and it also is the case that those medicines aren't only used for depression. They're used adjunctively in other mental illnesses or directly in some other mental illnesses and for some other purposes altogether.

But you know, also if you had gone back ten or 15 years, there would have been much less prescribing of antidepressants. I forget again what the numbers of it are. It certainly has gone up by one and a half times, you know, in the short period of time.

PROF. GLENDON: Well, one reflection is the one that is prompted by the thought. Those of us who are learning about this for the first time, I suppose, now the next time we walk into any social gathering, you're going to look around the room and say, "I wonder how many people here am I experiencing in some kind of pharmacologically altered state."

Of course, we all go to cocktail parties. So we're sort of —

DR. KRAMER: All there.

PROF. GLENDON: — to that, but more seriously, if this is a mass phenomenon and if the effects or Prozac are as you describe them, then how are we to think about the effect of that on our political and civic culture? That's one question.

And the other is whether you've changed your mind over the years since you wrote this book about the way you feel about Walker Percy. You seem to be, on the one hand, powerfully attracted by him, but ultimately, am I right that you're in disagreement with him? You think maybe — well, specifically his idea that it's very bad to be a castaway. I think he gets that from Heidegger, the "Geworfenheit."

It's very bad to be a castaway, but the one thing that's worse than that is not to know you are a castaway. He's thinking of that more in existential terms, but for those of us who operate at a more political level, it's somewhat alarming.

There are times in the history of a country when you think that there are things that people ought to be worried about and not going around what may worry.

So I wonder if you think that this mass use of these mood altering drugs has an effect on our political and civic culture.

DR. KRAMER: I think that the — I'm sort of a clearing house for Prozac complaints and information and crackpot schemes and so on. So that, you know, just by monitoring my answering machine and email I have some odd overview. And I don't mostly think these drugs are used trivially. I guess that might be a first step towards this social — I haven't seen these examples that people worry about.

And, of course, it may be that you run into someone and they say they're on it to be more creative, but you know, if you really interview them, they're not on it to be more creative. They're on it — they were put on it for some very substantial reason usually.

And there are effects. I mean, I read something twice in The New York Times, once in the education section and once in some other article, where the health services at universities are complaining that they're getting sicker children, sicker young people because the people who otherwise would have been handicapped or hamstrung by depression in high school are on these medications which, say, work for them for a year, a year and a half, whatever, and they do well enough to get into a higher level college, and then the health service has more children who, you know, started out more depressed to begin with.

And I think we would say that is a good thing, you know. That is assuming that we don't have some other concerns about the medication and their long-term effects and so on, but merely that more depressed young people are entering into ordinary productive behaviors more successfully we would say is a good thing.

And I suspect that that is the major effect, and I think one reason we're hearing about things like accommodation in the work place for the mentally ill is that there are more depressive people successfully in the work place, and then they're having whatever trouble they have on top of it and, you know, what is the right accommodation for them?

So that on the whole, I think, you know, on a public health basis the first thing to say is recognizing depression, treating depression is probably much more important a problem even where we are now than worries about overuse of medication.

I think I'm very prone to ambivalence myself, and I don't know if I'm much changed with regard to Walker Percy. I've thought a lot about, you know, what I value in myself. You know, do I value my ambivalence and so on?

And I think a lot of my work comes out of worry and empathy with depression and so on, although at the same time I think any time I've had a chance to cast some of that aside, I have done so quite willingly.

And I think, you know, if we had the opposite, if we had a medicine or a procedure that made people less confident and more troubled and so on, there would be very few takers for it, you know.

I think depression is one of the things we value very much in others or in this "faute de mieux" way where people write memoirs of depression and they say, you know, "But there were all of these things I got out of the depression."

And you say, "Yeah, right." I mean, that's true. In every life one gets things out of what it is one experienced, but you know, they really have worked very hard and the same is true in earlier eras. I mean, you know, what if van Gogh had antidepressants? Well, you know, van Gogh was on, I guess — was it arsenicals? He was on digitalis. He was on high dose digitalis as a sort of antidepressant, anti-epileptic on the general sense that if you slowed things down, these people with manic depression would do better, and there's this story about whether one of his yellow paintings is related to medication side effect.

I mean, there hasn't really been a time where people haven't wanted to very vigorously diminish those traits. I don't know if that — oh, let me give the real Percy answer, which is I think it's the same answer about freedom.

That is, yes, I want to be troubled by things that are legitimately troublesome, and no, I don't want to solve all of my problems by going to the Gap and buying another pair of clothes to feel that I'm being rewarded as a consumer.

But at the same time, it doesn't seem to me that there's a lot of inherent nobility in suffering that is mere biological happenstance.

PROF. GLENDON: I have one short question about the effects of Prozac. Does it affect people's ability to conceive and plan long-term projects, to think about the future?

DR. KRAMER: I mean, I think it may, but you know, I think it may be one of these sort of parabolic curves, if I have the right shape, where, you know, if you're depressed and now you're less depressed, you can certainly plan where you couldn't before. Whereas if you're manic, you know, you're sort of throwing off all sorts of things without choosing well among them.

It may be that that's one of the — in terms of main effects, I think that's the spectrum. I think in terms of the side effects of apathy or failing to care adequately, you know, that that is just a problem on a number of dimensions which would include planning.

CHAIRMAN KASS: The queue is longer than we have time for. So let me call on a few people now. We'll take a break and we'll hear from Carl Elliott, and then we'll continue.

I have Rebecca and then Paul McHugh. We'll see where we are when those two are done.

PROF. DRESSER: I wonder if you think about a different kind of group of social effects, I suppose economic. So does it bother you if drug companies are focusing a lot of resources on, you know, the next Prozac or after the next whatever, the next thing in this so-called cosmetic area, as opposed to, you know, all the many others, even if you limited it to mental illness, the needs that are out there?

You know, its effect on priorities, either drug companies or, say, federal funding or what's covered by health insurance, given, you know, increasing pressure to cut cost and people are losing insurance.

I mean in the real world, these are the questions that bother me, sort of allocation of resources and priority questions.

DR. KRAMER: Yes, yes. I'm very worried about that. I mean, I think we could have started the worries earlier. I actually think that, you know, doctors who go into cosmetic surgery where that is not plastic surgery for cleft lip and palate and burn victims, but for taking normal people and making them look more attractive, should have to at least pay back the subsidized costs of medical school, to the medical school that I went to medical school.

I mean, I think, you know, that really there is a distinction between treatment and enhancement, you know, that we want to be able to make, and that treatment really is the priority. There's no doubt that treatment is a humane consideration, and there is doubt about enhancement.

I do think that most drug companies are working on treating mental illness, and there's an enormously long distance to go in treating mental illness, but because of the way brain pathways work, because you're really working on developing things that attach to receptors or, you know, all of those methodologies, it seems to me are going inevitably to produce substances that are as likely to change temperament as they are to treat mental illness.


DR. MCHUGH: Peter, it is wonderful of you to come and to talk with us in this way, and I wanted to begin by telling you that, while I like you because of your gifts and your generosity, your handsomeness, your height —


DR. MCHUGH: — what I value in you, why I think you are a remarkable psychiatrist in America, and I've said this to many people, is that you're one of the few psychotherapists that really listens to his patients and drew from what the patients said not a conclusion about their particular insights that you delivered, but that maybe the pill that you were giving them was doing something quite remarkable, and it took a lot of other people a much longer time to recognize what you did and, therefore, you advanced the field tremendously, and I value that.

And in the questions I want to ask you now is I want to know if I can get you to move along a little bit further along the same directions, of course, that you went.

First of all, you are talking in DSM-IV and DSM-III terms a bit, and you and I know, and certainly Charles knows better than anyone else, that that's a very poor lead for us to know what we're talking about really because DSM-IV is a nomenclature. It's a dictionary. It's not even a classification like we have.

And, therefore, the terms that we get to use may be too loose for us to carry the kind of weight that you want to carry in ethical terms. For example, because we don't have yet a solid foundation on the biology of depression, we cannot tell whether we're dealing with one subject that is a spectrum or whether we're dealing with the fact that there may be a particular disease in which something broken, just like tabes dorsalis is a broken thing. Epilepsy is a broken thing, and that there are other conditions that both of them are affected by Prozac, but they might be different.

So, for example, bipolar disorder, of which depression is one and which you haven't talked about as specific depression, that might be clearly a broken part, and if we could find out what that broken part would be, we might want everybody to get fixed up just like we did before we discovered things about epilepsy.

We're very confused about the range of epileptic phenomena, out to fainting and things of that sort. We're quite clear about what epilepsy is now and how different it is from swooning.

Now, to bring that around to what we're talking about, but just as an aside, by the way, you talk about what we want. "We" might be a very special group, we guys that grew up in New England and all, because there are lots of people, you know, following Michael's view, that were not terribly pleased with psychoanalysis not just because of the theories, but because of the kind of being that it promoted.

I mean, the idea was that you signed out, and there were plenty of people that said, "Well, gee, what would have happened to van Gogh if somebody psychoanalyzed him?"

You know that. I'm telling you things that you're perfectly aware of. So what we're coming down to and what's concerning lots of us in this conversation and, I think, concerning you is whether the things that we're driving for are really what Aristotle would call, you know, "eudaimonia" or whether we're talking about Joe Campbell's bliss. Is that really the pursuit of happiness, is to chase a bliss, and if we get a drug for bliss, is that really what we want?

And, secondly, are you talking about wanting to support and find value in — value by the way that I don't share — in issues that are common and are called depression, but really are the state of mind of fundamentally unstable introverts? You know, unstable introverts are okay, but they don't necessarily —

DR. KRAMER: Paul, I want to go back at some point and ask you how you ever became a psychiatrist.


DR. KRAMER: Because they only let unstable introverts in.

DR. MCHUGH: Spoken like a psychotherapist. An interpretation.

But what do you think, Peter? Do you think — these are all tremendously important questions that you've raised, and I've loved listening to you, but do you think they're going to shape up and fall out? When we start instead of using the word "depression" and even your word "melancholia," we're going to start using words like demoralization in a certain situation, the common state of mind of unstable introverts, the mode of being that is more aggressive and assertive rather than more accepting. And in that way we might be able to get to a point where we could agree or disagree about what we're doing instead of bringing this medical stuff all in with it. Okay?

DR. KRAMER: All right. Well, thank you for the lead-in. I really appreciate the lead-in, and you know, as usual, you've gotten the exact issues, which I am probably not going to answer well.

Right. I think it's very hard to discuss these issues without knowing what depression is, and we really don't know very well. A psychiatrist in the office throws away the DSM, and as I say, if you have a patient who has one or two symptoms, but they really look like career symptoms, you might think this person really is depressed. This is the real thing.

Whereas if you have someone who comes in and meets every bit of those criteria, but you see a lot of resilience behind that, and there's not much history going in and not much family history, you might treat that person very differently than the first one and really assume that although it looks on a phenotypic basis exactly like depression, you're just going to assume this person is going to get better on his own or on her own or with just a little support.

So that we are looking for some core ailment, and it may be that we're going to be able to pick off pieces of it. So let's say late life depression really is a vascular phenomenon. Well, we would all sign on to say we'd eradicate that. No one needs, you know, vascular problems in the brain late, late in life.

And so that maybe we'll pick things off, but my sense is that in the end a lot of depression is just going to look like what goes wrong when things go wrong in a certain direction, and some people are going to be more vulnerable to that and some less vulnerable.

And it's true that the hints of who is more vulnerable is going to be something like neuroticism. This might be a private discussion. I don't know, but I mean, that we can forecast who's going to have a lot of trouble, and the way that looks like is going to look like emotional reactivity in general.

So that's sort of how it looks now anyway, and I think that's what psychiatrists, you know, maybe not a lot of psychiatrists, but I think the psychiatrists who have thought well about this, or researchers think.

Then we are going to be stuck with problems like the ones I've talked about because it's going to look to the Darwinists as if those problems are really a way of getting mothers to attach strongly to their infants, by punishing them for loss of attachment or so. It's going to look like part of the normal human condition to be emotionally vulnerable in certain ways.

And the question is: there's going to be, you know, a very profound question, which is how much we want to play the hand that's dealt us, and how much we want to be free to do something which, yes, the medical profession could treat it as a predisposition to depression, but being really honest about it, what we're doing is freeing people from constraints that have been necessary human constraints or useful for the troop.

And you know, whether we want to do that is going to be a very serious question, and that's why at the end of that, everybody said maybe it's better to decide these questions now than when we know more because we're very much in touch with the whole tradition of caring about alienation or caring about approaching troubles with a great deal of ambivalence and doubt and worry and so on, and that maybe we ought to decide how we value those before it turns out, you know, that we can sort of pick them off piece by piece, attaching them to things that medicine calls ailments.

I may have said two opposite things there, but you know, that might be a fuller description of what I'm imagining.

CHAIRMAN KASS: Look. I'm somewhat arbitrarily — I've still got five of us in the queue, and there are probably others who would like to get in. Let's take a break, and let's make the break a little shorter, say, ten minutes instead of 15.

We'll have Carl's paper. Dr. Kramer will stay with us, and we'll continue this discussion once again.

(Whereupon, the foregoing matter went off the record at 3:20 p.m. and went back on the record at 3:36 p.m.)

  - The President's Council on Bioethics -  
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