Mr. MINSHALL. Doctor, do you have any basis for knowing what the individual States are doing in the way of research? I know you are familiar with New York. What is the country, as a whole doing?

Dr. KLINE. The country as a whole is in a very interesting condition. Again, as a fact, it has now been demonstrated that research in this field pays. I literally mean pays in the sense that there is a prospect that this tremendous burden can be lessened, with the result that many of the States are now attempting to set up research units within their hospital systems.

I have the discomfort of having to turn down at least 3 or 4 jobs a year which pay anywhere up to twice what I am getting from the State of New York, since many of the States, where they have had no research facilities, want to build such departments. The difficulty, of course, is, with many of them, that they are willing to pay very well for a research director, but they don't realize that, without supporting staff, he is practically immobilized.

One of the great problems, which, again, I will briefly refer to, is that there are now more positions than there are people. In point of fact, the pharmaceutical industry is making a contribution here, too. One of my close colleagues at the hospital, with whom I work a great deal with the drugs, was trained, so to speak, in the pharmaceutical industry. He spent 4 years working for a pharmaceutical house.

So the transition is not all from the professions into industry. This is not unique. There is a movement the other way, too. The people who have really been trained by industry are now moving back into this field because there are opportunities which didn't exist before. Mr. MINSHALL. Thank you.

Mr. MEADER. Dr. Kline, you don't have any figures on the amount of money provided by States or others, perhaps local institutions, that you could put alongside industry's contribution and the Federal Government's contribution?

Dr. KLINE. I could take an educated guess, if you would like, since I know what New York State is, and I know that relatively the support given in New York State is quite high, compared with most other States.

New York State has 120,000 patients on its books, which is something more than 10 percent of the Nation's mentally ill. The expenditure is roughly in the neighborhood of $2,500,000 for actual research. I wouldn't want to go to court on that figure, but I think it is roughly

correct.

If you figure this constitutes something more than 10 percent of that given by all State governments, the total would be about $15 million so that industry's contribution, if you use the 10 percent of their gross sales of psychopharmaceuticals, would be more than equivalent.

Industry, I would guess, is putting in the same amount or more than the State government of the 48 States, which is a significant

amount.

Mr. MEADER. Do you have a figure for the foundations?

Dr. KLINE. I could dig it out.

No; I brought everything else with me, but I don't think I have that one. I have it on the Federal funds. That one I brought. But I would guess that the Government is supporting about four times as much research in this area as are the private foundations. Actually, the private foundations have been relatively chary of this whole area.

There is one foundation with considerable money that won't support research in this field at all, because it is a kind of one-man foundation and the one man has the attitude that mental health is "Red." He derives this, I think, from the idea that these people are cared for in State institutions, which is a form of socialism, and he'll be darned if he is going to give any money to support such kinds of activities.

Relatively, however, the private foundations, until the last few years, have, with a few exceptions, steered pretty much away from this area as being one in which it didn't pay you to invest money. The foundation has the same problem. They have the responsibility of placing their money where it will bring about the greatest return in terms of their good.

Mr. MEADER. Your figure for New York State was an estimate of the direct contributions to research, not provision of hospital and laboratories?

Dr. KLINE. It would include laboratories.

Mr. MEADER. Or personnel such as regular people on the pay of their staffs?

Dr. KLINE. I am not talking about maintenance and care.

Mr. MEADER. It is over and above the State's contribution to the operation of your hospitals?

Dr. KLINE. I am probably quite high on that. Reconsideration would make me say that probably $15 million for the State governments is quite high compared to the actual figure. If I can find it, I'll be glad to send it along to you.

Mrs. GRIFFITHS. Mr. Chairman, may I ask a question?

Mr. BLATNIK. Mrs. Griffiths.

Mrs. GRIFFITHS. Is the research within these clinics an attempt to isolate a cure, or an attempt to test a cure, or both?

Dr. KLINE. You mean in the hospitals?

Mrs. GRIFFITHS. Yes.

Dr. KLINE. It varies greatly from one hospital to another. I would say in most of them, the attempt is at this point to describe what happens. Our own laboratories are perhaps illustrative to some degree. We spend at least 85 percent of our funds and our personnel on what we call basic research that is, studies with radioisotopes, enzymes, steroid metabolism, psychological problems, in terms of perception and so on, which are not related to the drugs at all.

Eighty percent of our effort at this point is to try to find out what the cause of mental disease is, or what mental disease is, because once we know that, then the possibilities of more effective and rational cures will follow. You can't invent a satellite or a guided missile if you don't have the basic research upon which to build it.

At this point, what is most badly needed is the basic research. which has been horribly neglected, since it appeared to be pretty fruitless to do any. The fact that we have now found chemical means of influencing mental disease has stimulated a whole area since, if behavior can be influenced chemically, it is much more likely that there is a chemical factor in the causation. This doesn't mean that it is all chemical, but it looks like now this is an area where there is some pay -dirt. Most of the research laboratories of which I know are at least in large part devoted not so much to testing drugs as to basic research. The support given by the pharmaceutical houses is "with no strings attached." That is, they will give you the money, and if at the end

of a period of time you tell them whether a drug they have produced is any good, or no good, or too dangerous to use, or the best thing since the invention of the wheel, they are perfectly happy and don't really care if you use the money to buy an analogue computer, which is one of the things we bought with some of our money from a pharmaceutical house. Thus, some of this money can be used for basic research. The other part is used for the drug testing.

Mrs. GRIFFITHS. Would you say that research for a pharmaceutical house is roughly what drilling for oil is to a Texan?

Dr. KLINE. No; I think it is, in a sense, learning more about geology and the formation of rock structure.

Mrs. GRIFFITHS. You get a lot of dry runs, don't you, researchthe pharmaceutical houses?

Dr. KLINE. Oh, yes. I think the figure is 1 out of every 400 preparations which are prepared reach the market. This is, then, a quarter of 1 percent of the products that are made that actually reach the state of being marketable.

Then they too support basis research within their own research. To use your example of digging for oil, they, too, are concerned with rock structure and problems of geology that don't have any apparent relationship to oil at all.

We are just beginning to recognize that without basic research applied research dries up. Some of the best scientific brains in the country are in these companies, and they are working not on developing a new modification of an already marketed drug so that it will be more marketable, but are working or very fundamental problems. The scientist doing the work doesn't care about marketability. He is interested in geology and the fact that somebody may come along and find more oil with this makes him happy, but he is much more happier if he finds out that in the pre-Cambrian era the atmospheric pressure was point something else or so on. This is his motivation.

Mrs. GRIFFITHS. Thank you.

Mr. BLATNIK. Doctor, time is running ahead. May we summarize— perhaps you could summarize any parts you have not covered on the rest of page 14 and page 15.

Dr. KLINE. Yes, I'll very briefly go into it.

Mr. BLATNIK. Úp to page 16.

Dr. KLINE. I mentioned a number of other ways in which pharmaceutical houses have given support that has nothing whatever to do with drugs such as supporting fellowships and things of this type. Then I would like to go to page 16.

As Mr. Blatnik has indicated, for a very specific reason, since I regard this as highly important, I would like to preface the critical remarks about the psychopharmaceuticals by a general statement which I very strongly believe should apply to myself and to all subsequent witnesses. I have sent this testimony to those of the subsequent witnesses that I know will appear.

That is, namely, that it would be not only inadvisable but highly improper and very much against the general welfare to name any specific drug as such. There are hundreds of thousands of patients in the country on each of these pharmaceuticals and any statement that the side effects of such and such a drug are dangerous or that a certain other preparation is "ineffective" unless backed by substantial and definitive proof may lead to discontinuance of treatment by the

patient against the best available medical advice. There is no evidence so conclusive at the present time that such statements can be made without qualification and until such is the case these are matters for scientific investigation; not public debate. Any witness who takes upon himself the responsibility of indicating that a particular drug is unsuitable for use should be fully aware that he is throwing into question the knowledge and judgment of the prescribing physician and should be prepared to accept the ethical consequences. If he has such doubts and opinions along with appropriate evidence there exist many proper means of proceeding through medical journals, societies, et cetera. To name specific drugs or drug houses is all the more immoral since it is not necessary to accomplish the purposes for which these hearings are being held and involves as a possible consequence the termination of treatment of a drug which may be functioning effectively. Therefore, I would like to urge against such derogatory public reference since it serves no useful purpose, is medically dangerous, and socially destructive. Like everyone else I have personal opinions as to the relative merits of various preparations, some of which I have expressed in the literature, which I believe is the more appropriate place, but until much more definitive evidence is available I believe that no categorical statement should be made before a committee so much in the public eye as is this group. As an illustration of how cautious one should be it is sufficient to point out that when we first introduced reserpine for psychiatric treatment it was declared dangerous and said to be ineffectual by many who had not even used it. Even today, having just finished writing a review of the 1957 literature it is evident that some investigators and clinicians using this same drug in inadequate doses or for inadequate periods of time have found results to be unsatisfactory. This may be true in respect to any of the pharmaceuticals and therefore the witness who presumes to such complete knowledge that he is prepared to demonstrate that other investigators or clinicians who have found it useful are completely in the wrong is assuming a tremendous responsibility which may do great harm and will not further the purposes of these hearings.

Fifth, to get into the heart of the matter, let me take up in order the various points of criticism and itemize means by which they are already being handled or could be dealt with.

(a) That investigators are quoted "out of context."

I think Dr. Ayd will confirm me that this is quite routine. It has been the practice of many pharmaceutical houses, when time permitted, to send to the individual investigator or clinician a letter requesting permission to quote him on a particular point. This practice has become increasingly more prevalent and it is now only when limitations of time make it necessary that permission is not so obtained. This does not gainsay the fact that in the past investigators have been so quoted out of context but I would like to point out there already exists a mechanism whereby this could be very readily handled. In an excellent paper Mr. George Chapman of a prominent New York law firm has summarized the situation making it clearly evident that an investigator or clinician, even though he is quoted from a published text, if he feels that this has been done in a manner injurious to his reputation or presented in such a way as to make him appear ridiculous can have recourse to the law courts under the law

of copyright and the doctrine of right to privacy. I would like to submit Mr. Chapman's paper as exhibit 3 since it cites legal precedents.

Mr. BLATNIK. Without objection, it is so ordered.

(See appendix, exhibit 3, p. 176.)

Dr. KLINE. I had meant, incidentally, to submit the editorial I referred to before as exhibit 4.

Mr. BLATNIK. You may do that now.

(See appendix, exhibit 4, p. 181.)

Dr. KLINE. I got so fired up by Mr. Chapman's letter that I immediately phoned him and obtained permission to quote him.

I have reviewed and considered at great length various alternative proposals such as making it mandatory for the individual being quoted to clear the "copy" in all cases prior to publication. None of these appear to be practical and would consume a tremendous amount of time involving the investigator and clinician involving himself with matters which are not germane to his work. Clearly though, if legal recourse is available and this is brought home by a court action there would be very little chance of the same error being repeated. Actually such a drastic measure would probably be unnecessary. My suggestion would be that in those cases where the investigator feels that he has been quoted out of context or in such a way as to misrepresent his real views, that he write to the pharmaceutical house involved requesting that a retraction or an amended statement be printed by them in the same mediums in which the original claim was made. If for any reason the pharmaceutical house were unwilling to do this a letter to the journal of the American Medical Association or the American Journal of Psychiatry detailing the correspondence would certainly produce an effect that would forestall another error.

Mr. PLAPINGER. You referred to the mechanisms to correct quotations out of context.

Dr. KLINE. Yes, sir.

Mr. PLAPINGER. These mechanisms have always existed. Isn't that so?

Dr. KLINE. Yes, but I think there has not been an awareness that they did exist on the part of the people who felt injured by being quoted out of context.

I think one of the useful functions of the hearing may be that it will bring to attention mechanisms whereby this can be corrected under already existing laws.

Mr. PLAPINGER. It would seem to be almost a reflex action that if you, as a scientific author were quoted out of context, you would write to the medical journals, and possibly as a last resort, have recourse to the courts. But this is time consuming, and what happens in the interim with respect to the publication of the quotation out of context?

Dr. KLINE. You in a sense have very nicely anticipated what I wanted to say, which I am happy about, because it must be sound thinking if this is your way of reasoning.

I have reviewed the various alternate proposals, which I won't go into to save time, but none of these appear practical.

I think, as you have pointed out, that recourse to the courts probably is unnecessary. My suggestion would be that in those cases where the investigator deems that he has been quoted out of context or in such a