Friday, January 17, 2003

CHAIRMAN KASS: This time was set aside for council's discussion among ourselves as a follow-up to the conversation we had at the last meeting in connection with Dr. Diller's presentation on Ritalin, and Dan Foster already, I think, yesterday in his comment at the end talking about -- I've forgotten the adjective, Dan -- but it was big, small, and something ?-

DR. FOSTER: Semi-momentous.

CHAIRMAN KASS: Momentous.

DR. FOSTER: And non-momentous.

CHAIRMAN KASS: Okay. I'm sorry. The gray cells are --

DR. FOSTER: I can see that I made a big impression on you there, Mr. Chairperson.

(Laughter.)

CHAIRMAN KASS: You made an impression in terms of the content, the term I lost, and Dan suggested, in fact, compared to choosing sex of children, the question of the medication of our children with psychotropic drugs was certainly semi-momentous or momentous enough to be worthy of further attention.

And I must say after having listened to most of the things that we've been through when we've had our outside presenters speaking to us about beyond therapeutic uses of these new agents, perhaps because that one is already here and on a large scale, but also for the thing itself, that one made a huge impression on me as something worthy of more attention.

I mean, one has a growing reliance on the medical model of behavioral disorders, reinforced by the fact that whether specific or not, you get certain kind of therapeutic -- some kind of benefit from giving the medication. Ritalin improves everybody's performance regardless of whether they have a disease or not.

You have vague diagnoses and hard to rely on criteria. You have parental demand, school insistence. You have economic pressures to reduce the costs of more time consuming intervention. You have direct company marketing to the consumers, and you have very limited experience in the testing for the long term effects both in terms of bodily harm, but in just sort of human terms, what this means to have produced a culture which is now increasingly medicating our children.

And I included just for take-home consideration this recent report. It's a mere crude utilization report over the decade from '87 to '96 which shows that there's been a two to threefold increase in the use of psychotropic drugs in youth. They haven't been able to follow up in particular as to whether this is reasonable or not, but the estimate is this is now seven years ago. Roughly six percent of youth have already been on at least one or another psychotropic medications.

This does begin to look like something like professional self-regulation or control of medical practice, and I'm not sure exactly how to even begin to think about what one should do about this, but I do think, at least speaking for myself, I thought it was a worthy enough topic to bring before us to see whether this is one of those case studies that would benefit from our further attention, and if you agree, to see if we can have some suggestions as to how we could fruitfully proceed in this area.

I know, Frank, you've written on this and probably thought about it some. There are probably others in the room who have some reaction, but this is really an opportunity just talking through amongst ourselves and see what we think about it and see whether it's worthy of some further consideration and, if so, how to go about it.

Frank, would you get us started, please?

PROF. FUKUYAMA: Well, one thing that has become clear through several of these meetings is that before you get to, you know, the problem of the neuropharmacology itself, you've got this underlying problem in the discipline of psychiatry, which is the whole, you know, notion of what a disorder is and what pathology is.

And this is something, you know, that Charles and Paul particularly have spoken to, you know, since they have been direct participants in, you know, the DSM process. But, you know, the underlying problem is that you've had this highly, you know, political process of getting things classified as disorders with no, you know, clear biological basis, with, you know, very little consensus as to compared to somatic medicine as to what constitutes a disorder, which has then led to the political process driving this perpetually expanding domain of what's considered therapeutic.

And unless you can solve that underlying problem, it seems to me that it's going to be very hard to address, you know, certainly the regulatory problem or any of the, you know, problems of the uses of specific drugs because they're all meant to treat, you know, these things that are officially classified as disorders, and so that's the prior problem.

So I would think that, you know, a little bit of discussion and research and background into that, you know, set of issues would be appropriate, and I think Paul, you know, is probably as good as anyone, you know, to lead us in that.

CHAIRMAN KASS: Dan Foster.

DR. FOSTER: Another thing that I would like for the group to consider is the possibility of hearing from an expert in the issue of addiction to drugs and the potential of creating significant, maybe even mass addictions to different types of drugs and the biology of addiction, which is progressing very interesting.

Just as an aside, I don't work in this area, but having to deal sometimes with not only patients, but physicians and others who have become addicted to drugs, for example, my own impression is that amphetamine addiction is the most difficult addiction to break. There's a 96 percent recovery rate in physicians who become impaired, if they're using Demerol or other things, but amphetamines in my own personal experience -- I don't know whether that nationally occurs -- is the hardest thing in the world to break.

Even the runs, as you know, you know, a cocaine run means a continual use for a period of time. A cocaine run may go for a day or something. Amphetamines, they go for a week, ten days, and you know, they lose weight. I mean, they're just wasted away.

I meant the stimulant drugs, the methamphetamines particularly, which are growing in intensity in the illegal market, I have the same concern about quasi-amphetamine-like drugs that are being used. I at least think it would be helpful to hear about that.

We've talked casually from the newspaper about the fact that the military is using Dexadrine, which is a long, old drug. It works terrifically, but it has been raised in the issue of the pilots that are undergoing their grand jury interrogation as to whether there will be a court martial and so forth.

I mean, I don't know what the effect of this is going to be. I mean, I really don't know what's going to happen to all of these kids, and I certainly don't know what's going to happen to college kids and people like that who are taking these things. I think they're pretty hard to break once you get on it.

So to me this would be a useful adjunct to the whole problem of enhancement to get back into the issue of risk that is involved with this sort of stimulant and other activity.

CHAIRMAN KASS: Michael and then Bill, Charles. Let's go in order here.

DR. KRAUTHAMMER: I want to take up on Frank's point about the fact that this proliferation of drugs really is at least in part a result of the chaos in psychiatric diagnosis.

I was involved in the formulation of DSM-III, and in fact, one of the reasons I quit psychiatry is that I reached a point of such despair about the solidity and validity of psychiatric diagnosis, and it's clear to me Frank is right, that this explosion, this doubling or tripling of the use of drugs in adolescents and in children is clearly a result of the fact that it has all been opened wide by the vagueness and the often arbitrariness of psychiatric diagnosis.

It's as if a psychiatric diagnosis is sort of the wild West. There is no law, and anybody can come in and stake his claim and claim that they're treating an illness when we're not even sure what that illness really is.

The problem though with looking at it only in that way is that there may not be a solution to the problem of psychiatric nosology in our lifetime. It's a problem that's 100 years old at least, and it's not going to have any near term solution.

So I think what we could do usefully would be (a) to recommend that perhaps -- I'm not even sure that it would be taken seriously -- a recommendation that there ought to be more work and more precision an psychiatric diagnosis, but at least what we could do is to highlight the alarming rise in the use of these drugs.

The fact is that we have what, almost six percent of our kids being medicated, and what essentially we're doing in many cases, obviously all of us know of the cases of the kids who are out of control whose lives are ruined, ruining other lives, who need help. But as we heard the other day, it's a fairly small percentage of those who are getting this. It is mostly an instrument of social control, the pacification of young people, particularly young boys, to make things in life easier for their teachers or parents or surroundings, sometimes for the kids themselves.

I think we ought to highlight it as a problem, as a serious problem and one that merits attention. I think that ought to be the beginning. Obviously we're not going to be talking about prohibitions or regulations yet, but it's clear from the paper that was given to us by Zito that so little is known about this.

I think we could start by making a strong recommendation of the study of the causes and the justification for the tripling or doubling of the use of these drugs in this population.

CHAIRMAN KASS: Charles, can I follow up?

I mean, are there types of people from whom we should be hearing?

Dan Foster suggested that the addiction aspect of this is one piece of the thing that's very important to us.

DR. KRAUTHAMMER: Well, I think we need to get someone who has worked in the field of psychiatric nosology. I left that field 25 years ago. So I don't know who the great leaders of it are now, but that should be fairly easily ascertained.

I think we ought to hear about the proliferation of the diagnoses, how the diagnoses are made, how political they are, you know.

One of the diagnoses that we heard about last session was -- what was it? -- social --

DR. KRAUTHAMMER: Oppositional disorder. How in the hell did that ever get into the DSM? It would be interesting.

So I think we'd want to have a short presentation on the sort of history and the status, the psychiatric diagnosis, as a starter, and probably also, I'm not sure whether the data is known, but some long term studies of the effects of these medications, both medical and social, on the kids.

But I think that would be a starting point and perhaps as Zito or someone, an epidemiologist, to come and speak to us about simply the change, the radical change in the rates.

You don't usually get an inkling of an incidence of a disease in ten years. Obviously it's either an artifact or a diagnosis or something in the water supply.

DR. FOSTER: One of the problems, as I'm sure Charles knows and Paul would speak to that, is that psychiatry is riven into two camps. There are the biological psychiatrists who are very interested in the genetics and the chemical backgrounds of diseases. They would not be the perpetrators of the marked growth in diagnoses, I think.

And so, I mean, the biological psychiatrists who, you know, apply all of the rules of ordinary science to their studies, including studies of addiction and so forth, are going to be different from somebody who -- I doubt that very many of them are involved in DSM. I don't know. So --

DR. KRAUTHAMMER: Well, I hate to say this, but, in fact, the leading forces for DSM-III and IV were the most medically oriented psychiatrists. What they wanted to do was to get psychiatry to replicate sort of the nosologic structure of regular medicine by doing it all phenomenologically.

So it was not by Freudian theories of the mind or instincts. It was about listing of phenomena, grouping them into illnesses the way you do in diabetes.

So the instinct was to medicalize psychiatry, but of course, what happened was in the process of doing that, politics obviously reared its ugly head. Some people wanted some diagnoses for political or ideological or philosophical reasons, included, and there was no resisting that. So it proliferated.

But the instinct was a scientific one. It was not, you know, the Freudians or the animists among them who pushed this. It was all from the scientists.

DR. FOSTER: Well, it's interesting. I mean, if you just listen to the dialogue, I mean, like we have a huge -- I mean ours is very biological. They usually seem to me to be critical of this thing, but it may have started that way.

CHAIRMAN KASS: Yeah, I have Michael and then Bill.

PROF. SANDEL: I agree very much with the agenda that's emerging from the suggestions of Frank and Dan and Charles, and I would just like to add one other suggestion that we look into another important component of this.

Charles spoke about the water supply that may have generated this, and one very important ingredient in the water supply and by no means the only one has to do with drug company marketing practices. And so I think that in addition to the sessions that we've been discussing on the way the DSM is written and how and why and the medical aspects, it would be useful to have, if we could, a staff background paper on marketing practices including the percentage of drug company budgets that are allocated to marketing as compared with research, for example, in the case of these particular drugs; increases over the period of time that we're looking at in drug company profits in these areas, as well as in the marketing efforts; direct to consumer marketing, whether that takes place with respect to these drugs; and other less visible forms of marketing, what are they and how those budgets changed during the period of time that we've seen this increase.

That just by way of gathering data, but for purposes of a session to discuss it, I think it would be valuable to hear both from someone who is an expert in this area and perhaps a critic, and then on the other side, to invite one of the marketing directors of the drug company that markets these particular drugs so that we could have a discussion with both of them and discuss this aspect of the problem along with the others.

CHAIRMAN KASS: Thank you very much.

Bill Hurlbut and then Bill May and then Rebecca. We'll just go around.

DR. MAY: The UT Southwestern sponsored conference drawing people from all over the country on the value assumptions in DSM-IV, and we might take a look at that volume in thinking through whether there are people who might be helpful to us on that subject.

John Sadler was a local host to that conference, but I can be in touch with you about that.

CHAIRMAN KASS: If you'd get us the reference, we'd be delighted.

DR. MAY: Yeah, yeah. The second comment, something that reaches beyond, I guess, the scope, but we have talked about opening out to the whole larger culture. There is a question of the relationship of addiction and overuse to the kind of structure of the educational system. I mean, it's not simply marketing. It's not simply loose diagnosis and prescription filling.

We did talk about the sweaty palms of the pianist, and there's the question do you simply walk away from performance or do you take things that will solve that problem, but so many kids live in the setting of society in the meritarian culture where you don't walk away from what is taken to be successful performance in the setting of the school system because it's the gateway to the future, not simply like walking away from simply one skill, playing the piano.

And so it reaches out and the whole question of the linking of our education system to this issue, and I'm not sure how one thinks about drawing in people, but I hope we don't forget that.

CHAIRMAN KASS: Well, thank you very much, Bill, and I'm reminded as we go around the room of the very end of Dr. Diller's presentation when he sort of made a kind of long list of the things that were somehow relevant to this problem or the things that would have to be addressed if one was going to get a hold of this, and it was dispiriting because of its magnitude.

On the other hand, it's in a way quite apart from what one can do about this. It would be, it seems to me, a useful service to show how you start with what looks like this little pill for this little use and how it reaches out into all of these different dimensions and illuminate various features of our society that conspire to this practice, which in itself is worrisome not only in itself, but as a symptom of other kinds of things that we're concerned about.

I take it that that's the spirit of many of the comments.

Bill Hurlbut and then Rebecca.

DR. HURLBUT: Well, in the spirit of what was just said, I think, first of all, I think it's extremely important territory for us to get into because we have the chance at this point in the development of science to get in at the bottom of this before the new powers of pharmacogenomics and so forth kick in fully and we can anticipate.

But along with that we need to be -- if we're going to anticipate what kind of problems might be coming down the line, we also be very realistic about what isn't likely to come down the line. And I think we should do this within the larger frame.

I, for one, would like a general presentation about what the whole scope of the picture might look like as we go into this, and I'm thinking specifically of what's being done in the way of drug development. That's at least one aspect of it.

With the sequencing of the human genome we're opening up vast numbers of protein targets. Our current armamentarium of drugs addresses a mere maybe 500 protein targets, and they estimate the number of new protein targets increasing at 1,000 a year and may go as high as 20,000 new, very practical targets.

So we're looking at a geometric increase in the number of potential intervention, sites of intervention, and I'd just like somebody to put that in perspective and give me a sense of what that new knowledge combined together with combinatorial chemistry, which is a way of producing and screening vast numbers of drugs very rapidly. That is having mixed efficacy, but it looks promising.

Also, there are new investigational tools I think we should be aware of. They're combining drug studies now with MRI, for example. They're getting away from just self-reporting and observation behavior. That's very important.

Just put those in perspective and see what's coming. Secondly, I think we need to have some kind of a difficult assignment, but some kind of a conceptual frame to put this stuff in. We have to be careful as a council not to get drawn into what happened in many realms of bioethics 20 years ago when the genome was being sequenced, where an awful lot of unrealistic scenarios were promulgated as not just probabilities, but inevitabilities.

And I think we need to be very sober and sensible in the use of our science here so that we're not chasing ghosts, things that never existed.

So in order to do that, I'm thinking specifically of the dangers of reification of human qualities, saying we're going to have drugs to do things which are, in fact, just very broad categories and are the complex interweavings of many dynamics and agents within the body. That's a big error we could make, and there are several of those kind of errors. Spurious localizations is another one, and improper quantifications, misplaced causations.

There are a whole series of these, and it would be very good to lay those out so that we saw clearly what we were doing.

I had wanted to mention also the scope of marketing concerns, but just to add to what Michael said, marketing actually influences the way a culture sees itself, and that, I think, is vague, but we should be realistic about it.

And then finally I think we should define the scope of the likely problems, having laid that foundation in. We're looking at a situation here where psychotropic drugs could be in a whole range of ethical concerns ranging from just trivial lifestyle misuses that sort of degrade humanity all the way up to the most complex issues which I think would be the most difficult bioethical issues ever, and those are the meaning of human responsibility.

So I think we're looking at an inevitable trend in our century of the medicalization of criminal behavior, and this is something that a proper frame might give us some way of entering into before it's thrust upon us as a practical problem.

CHAIRMAN KASS: Thank you. There are a number of good things here.

DR. KRAUTHAMMER: Leon.

CHAIRMAN KASS: Charles.

DR. KRAUTHAMMER: I think this might also be put in the context of the larger issue that we talked about, which was psychotropic enhancement. I think when you do it in adults, it would be a hard subject for us to tackle because it would be a recapitulation of the old debate on drug legalization, and I don't think that we want to do that.

But I think what makes this a special case and an alarming case and important one is the fact that it has to do with children who obviously are having this imposed on them.

So I think it makes it an acute problem and one that would highlight the other problem and allow us an entry into it. I mean, essentially what we're doing with this generation is we are getting them off nicotine and injecting Ritalin. That is sort of the summary of the last 20 years with all of our public education efforts.

And then I would ask how much of an advance is that. So I think it might be seen as a wedge into the, if you like, the enhancement issue in a very specific way and in a way that I think would be very publicly understandable since we're all sensitive to the imposition of these things on others, and this is stuff that's not voluntarily chosen. It's mandated.

CHAIRMAN KASS: Michael wants a tiny intervention.

PROF. SANDEL: I see the political appeal of that, Charles, but I don't think that morally speaking that's a relevant distinction or one that we should lay too much emphasis on because that suggests that what's wrong -- and we can awaken the public to this wrong -- of the use of these drugs in children has only or mainly to do with the fact that they're not yet at the age of consent.

But consent or the lack of consent is not the main thing wrong with enhancement. In fact, if enhancement in adults is fine, morally permissible, unobjectionable, then parents have the responsibility to improve their children, to promote the good of their children.

So we can't beg that question. If it's a good thing for adults, then it's fine, notwithstanding the fact that children don't consent because they're simply promoting the good of their children by giving them enhancements.

So I don't think we should detach this from our general enhancement project, and focusing on consent as what separates children from adults runs the risk of obscuring the general questions that we've been wrestling with in the area of enhancement.

If it's bad for adults, then of course it's bad for them to impose it on their kids. If it's good for adults to improve themselves, then they have a responsibility to promote the well-being of their children.

DR. KRAUTHAMMER: The point I was making is that it was not a moral but a political point. I think if we are going to start with its use in adults, we are going to have very difficult discussions. I think that we've seen that here already, definitions of enhancement and questions about why it's a problem.

I think what we can do is our entry into this issue, starting with a population that's defenseless, I think will highlight what the issues are. I wasn't making a case that this is purely a question of autonomy. I'm saying it makes it much more acute.

CHAIRMAN KASS: Also if I might, just a tiny point. Charles, when he first spoke, was talking really about behavior control of others, not necessarily for their own enhancement. So I mean there's that additional dimension here that might be brought out in this case, a constriction of -- well, Rebecca, please.

PROF. DRESSER: I would like to hear about the role of the private sector in promoting enhancements for all ages. I do think it should be an element of our report on enhancement. We might have a section that addresses it in the context of children specifically, but if we think about trying to speak to a broad audience, I think many people who might not respond to some of our other concerns might respond to the problem of drug companies and others with a commercial stake not just promoting, but not talking about benefits honestly, that is, trying to distort research findings or report them in ways that are not as accurate as a disinterested person might put them, the kinds of research that are done, all of the conflicts of interest, and so forth.

I think those are concerns that many ordinary people would respond to.

Also, even if we are -- with some items, we don't want to say, you know, prohibit them. We would express moral concerns about their use, but when people are trying to exercise autonomy, they need accurate information, and the chances that they're going to get accurate information about a lot of these things are reduced by the role of the private sector.

So even people who are very concerned about autonomous decision making would be concerned about that.

CHAIRMAN KASS: Janet Rowley.

DR. ROWLEY: I'm sure that you and the staff will be in close contact with both Paul and Mike to get suggestions.

CHAIRMAN KASS: Yes.

DR. ROWLEY: I think an area that is moving very rapidly but still in its infancy is the understanding really of the chemical nature of the interactions of various cells within the nervous system and the genes that regulate their function and the differences of gene products in patients with different kinds of disorders.

And you know, I understand Charles saying -- and I know nothing about this area -- but that from his perspective one of the problems of DSM-III and IV was its medicalization. But I think what we're just in the beginning of seeing is that that medicalization, if you will, is being put on a scientific ground of these genetic defects or these genes and their regulation are what may be contributing at least in part to schizophrenia and bipolar disorders and other things.

To the extent that we can become more informed on what's really known about these particular areas that would impinge on presumably these drugs, therefore, are targeting the regulation of these genes or effects of gene products, I think that that's important.

Whether one should also or whether as a part of that one would include studies on genetics and inheritance of these things because it is clear even going back to addiction that there are some families where people are prone to addiction, and I believe that some understanding of what some of the factors are, particularly the genetic factors and the genes that are involved, are being understood in some of those conditions.

DR. KRAUTHAMMER: Can I just make one point? I wasn't critiquing the attempt to medicalize psychiatry. I'm all in favor of it. In fact, that's why I went into it.

All I'm saying is that at the time when this was begun 25 years ago there was no sort of physiology you could do, rely on, and correlate to. So all that you could do is to group phenomena. You would observe symptoms. You'd put them in categories, call them diagnoses, and thereby imitate medicine.

But the problem is that without the physiological correlates, it was fairly arbitrary, and it's that arbitrariness which, of course, opened it up to all kinds of ideological and political corruption, and that's where we are now unfortunately in this area.

CHAIRMAN KASS: Other comments on this?

I take it that mindful of the massiveness of this topic we are encouraged to pursue certain crucial pieces of it from a better understanding of the actual biology that might, in fact, warrant the further medicalization of this to questions of diagnosis, questions of conceptual frameworks, questions of marketing, questions of certain meritocratic pushes in the schools and in the culture, and without knowing where this will take us, but certainly we have an opportunity to highlight a potential set of problems or problems which may, in fact, already be here, and by calling attention to them, require an encourage further careful study and examination of this, we could make some kind of contribution here even if the thing is much too big for anybody simplistically to try to wander in and say, "Ah, we have, in fact, a new enhancement which will make this problem go away."

DR. KRAUTHAMMER: Can I make one statement?

CHAIRMAN KASS: Please.

DR. KRAUTHAMMER: I think it may not be that unruly. I think there are three elements in here: the vagueness of the diagnosis which allowed the introduction of two outside forces, (a) the pecuniary, the marketing, and, second, the ideological and political and the social control, if you like, or socialization of children through the use of these medicines.

So I think there are three elements: the diagnoses which sets the stage for the introduction of outside forces, economic and ideologic. I think it's a very interesting case study, and I think it's one that concerns a lot of people and will draw a lot of attention.