This study was done here in Chicago under the auspices of the University of Chicago Medical School. In this study by Dr. Schuster, who, I believe, is still here in Chicago, and Dr. Jerry Jaffe, who was here at that time, narcotics addicts were given free access to methadone, codeine, or Pentazocine or a placebo. It was found that when addicts were able to get these drugs legally with no problem, they would take methadone and they would take codeine, but they would not take Pentazocine any more than they would a placebo.

Then they set the study up so addicts were paid if they came back and got one of these drugs. And still they did not come back for pentazocine any more than they did a placebo.

It was because of information such as this that when the Federal Government considered pentazocine back in 1974, the advisory committee on the Federal Government-I believe it was 12 nationally renowned scientists in this field-unanimously decided that the evidence did not warrant Federal controls at that time on the basis of what was known.

Despite this low level of abuse and dependence, as part of our general program of monitoring the medical effects of pentazocine, we began a special program in 1969 to collect reports of dependency and abuse, evaluate and analyze them and make them available to any interested responsible party as source data. This was not required as part of our program. These analyses have been routinely submitted to the FDA and are available to your staff. The type of misuse has remained much the same over the years, with the one exception that will be discussed in some detail later, the problem that we are really addressing today.

Mr. NELLIS. The problem what?

Dr. SPEIR. The problem which we are really addressing ourselves to today, street abuse.

A second internal program was begun in 1969 to insure the security and monitor the shipments of pentazocine. By 1974, when a number of our operations became computerized, we instituted a program of automatically flagging all orders over a certain dollar value or orders which represented a substantial percentage increase over the average of the previous 2 months. Such orders could be filled only when they appeared to be consistent with previous sales to the supplier in question.

Over the past several years, the system has detected several situations in which an inappropriate distribution of the drug may have been taking place, and steps were taken to reduce such orders to appropriate sizes, where warranted.

The problem during the past year in Chicago was complicated by the fact that one of the five major wholesalers in the Chicago area went out of business. The resulting increase in sales of all our products to the remaining four wholesalers in this area obscured the increase in pentazocine sales to a limited area of the Chicago south side that undoubtedly did occur and which was probably related to the improper prescription and illicit distribution of a number of drugs in that area during the past year.

Mr. MURPHY. You have no doubt it did occur, certainly.

Dr. SPEIR. As has been testified by others this morning, as we look back on it, it certainly did occur.

Mr. NELLIS. Could I also ask in that connection, Mr. Chairman, you referred to the probable relation of the improper prescription and illicit distribution of a number of drugs in that area.

What other drugs do you know of that were illicitly prescribed? Dr. SPEIR. From what I have heard of the Mohawk Clinic, it was practically anything they were sending out of there. But Pyribenzamine is one.

Mr. NELLIS. Pyribenzamine was almost always bought in concert with Talwin.

Dr. SPEIR. Right.

Mr. NELLIS. What I am saying is, do you know any other drugs that were subjected to the same type of illicit use?

Dr. SPEIR. Talking to people involved in this in Chicago, I have heard Ritalin mentioned, Valium mentioned.

Mr. NELLIS. In combination with Talwin?

Dr. SPEIR. No; not in combination with Talwin.

Mr. NELLIS. You are saying there is a problem of Ritalin abuse in Chicago?

Dr. SPEIR. I do not know. I have heard that.

Mr. NELLIS. You have no evidence of that?

Dr. SPEIR. I have no evidence, aside from talking with three addicts. The only time I have had a chance to actually talk with people who have been taking

Mr. MURPHY. Proceed.

Dr. SPEIR. We first received reports of the mixed abuse of pentazocine with tripelennamine from the Cincinnati area of Ohio last fall. We contacted the office of the commissioner of health of the city of Cincinnati, asked for information concerning the problem, and expressed our desire to do whatever we could to help in understanding and dealing with it.

Shortly after, we received reports of the same nature from Syracuse, N.Y. We contacted Dr. Richard Dougherty, director of a drug detoxification unit at the Booth Memorial Hospital in Syracuse, and flew up to see him. We obtained records of the cases he had seen and agreed to keep each other informed of what we learned of what was then a puzzling new phenomenon.

At the same time, late last fall, we instituted a worldwide search of the medical and scientific literature. At that time we did not find any medical or scientific reports on the misuse of Talwin in combination with tripelennamine or any other antihistamine. There were, however, reports on the misuses of tripelennamine or Pyribenzamine tablets, either alone or with narcotics, dating back over 20 years.

The first article of which we are aware appeared in 1957 in the New England Journal of Medicine. It is a case report of the intravenous self-administration of crushed tripelennamine tablets by a narcotics addict. This is also the first article in which, to our knowledge, the term "blue velvet" appears. This term is apparently based on the blue color of commonly available 50-milligram tablets of the drug.

In 1965, an article in the Journal of Forensic Sciences described sudden deaths among narcotic addicts. These deaths turned out to be due to the intravenous injection of crushed tripelennamine tablets

in combination with narcotics. The deaths were associated with a problem of the heart and massive pulmonary edema, and were considered to result from the insoluble talc of crushed tripelennamine tablets lodging in the lungs.

In 1970 an article in the Annals of Internal Medicine described progressive pulmonary fibrosis subsequent to repeated injections of dissolved tripelennamine tablets in combination with narcotics.

In our search of the world scientific literature last fall, we found nothing concerning pentazocine and tripelennamine used together. Because the information we received at that time concerned a possible increased dependency of the mixture of drugs, we started studies at our Sterling-Winthrop Research Institute to see if the drugs together produced any greater physical dependency than either alone. Although the statistical analysis is not yet complete, there does not appear to be any increased physical dependence with the combination. In addition, although we were not specially testing for an increased mortality of the mixture, none was observed at the doses tested.

Incidentally, last spring at the Federal hearings when this question came up, I asked from all of those present whether there was any information on the pharmacological effects of this mixed abuse. No one had any.

Mr. MURPHY. Doctor, how do you account, then, for the 39 deaths here in Cook County from overdose of this and the coroner's report? Were you here this morning?

Dr. SPEIR. I was indeed, sir.

Mr. MURPHY. There has been testimony of 39 deaths and some 300 or 400 of these patients in first-aid rooms and emergency rooms all around the city and Cook County.

Dr. SPEIR. I am going to respond to that, Mr. Murphy. I will do so immediately, if you would like.

Mr. MURPHY. OK.

Dr. SPEIR. I would like to comment on these reports of 39 deaths in 6 months associated with pentazocine and tripelennamine that were widely circulated in the Chicago area by television and press and were probably responsible in large part for the climate of opinion that led to the recent strict controls placed on pentazocine. The number of these deaths reported in the press started at 39, then went to 40, and then 44. We understand it has now decreased to six.

Just prior to the hearings before the Illinois Dangerous Drug Commission, we received the medical examiner's reports concerning 36 deaths during the last year. Of these, one had no reference to pentazocine whatsoever and apparently was included inadvertently.

Of the 35 which we received and which we went over carefully, we submitted for evaluation to our outside consultant, Dr. Cyril Wecht, who is a forensic pathologist and a former president of the professional society of forensic pathologists. At the hearing in Springfield Dr. Wecht testified that of the 35 of which we had information, only one could conceivably represent a toxic death attributable to pentazocine. And in that one death, it was of a young woman, multiple drugs were found in her body. She was signed out on one of the reports as a codeine death.

And finally, there was no autopsy done,

The next two cases with elevated though not lethal blood levels of pentazocine were both deaths from gunshot wounds. There was one other single case with an elevated blood level of pentazocine. This was a known diabetic who died under circumstances that were not apparent and who had a very high level of acetone in his blood. This is consistent with diabetic acidosis. And again, no autopsy was done.

Mr. NELLIS. May I interrupt for a moment, Mr. Chairman? I don't think the committee wants to debate the statistics on the deaths, but I think it is well known that the committee has received a great deal of testimony from medical examiners. When they see a body with bullet holes, it is very simple, logical, sensible to ascribe death to the bullet holes. But when they examine blood and see a combination of Talwin and Pyribenzamine and note that, certainly some aspects of the use of these drugs must be involved in that particular patient.

Dr. SPEIR. It may be.

Mr. NELLIS. Dead or alive.

So whether you attribute their death to the use of T's and B's or what not is really not our concern. The fact is, and I don't think you want to deny it, many, many dozens of hospital incidents and coroners' incidents have discovered the use of this substance or these substances in these patients. Isn't that a fact?

Dr. SPEIR. There were blood levels found, but they were blood levels associated with a single tablet, the kind of blood levels you get when you take a single tablet.

Now, if you find a blood level of Dristan or some antihistamine in your body that you have taken because you have a stuffy nose, in someone who dies, do you attribute the death to that?

Mr. NELLIS. Well, the coroners have various ways of doing that. But the one statement I recall they all made is that if you have a body with bullet holes, it is very simple. You attribute it to the bullet holes. But they do make other tests.

And down in New Orleans, for example, the coroner there does make careful blood tests on a machine that he described to the committee. And what I am trying to convey to you and to ask you about is whether or not you, as representing the manufacturer of Talwin, would deny the evidence that has been shown to this committee so far with respect to the lethal possibility in these combinations?

Dr. SPEIR. I do not know of any blood levels that have been submitted to the committee. And a toxic death from a drug, Mr. Nellis, is usually based on a blood or a tissue level of that drug which is considered to be toxic because of past experience.

Mr. NELLIS. Well, the medical examiner of Cook County will be here. We will ask him to defend his findings.

All I am saying is Idon't think you want the record to reflect that the company that manufactures Talwin is denying that this is a serious abuse problem and that people are getting very sick from it and that some of them are dying from it.

You don't deny that?

Dr. SPEIR. I deny there is any evidence that has been presented to us that we have seen so far that there has been a toxic death from Talwin, aside from one case in which there are other, alternative possibilities. There is only one of those, I genuinely feel, Mr. Nellis, which could possibly be attributed to Talwin,

The question of mixed abuse has come up. As I say, when we went back to our labs in Rensselaer, we could find no evidence from the study that we have done of an increased toxic effect from the two drugs, although the study was not set up specifically to look for them. Mr. NELLIS. You could not find any evidence of toxic effects of a combination of Pyribenzamine and Talwin?

Dr. SPEIR. That's right, sir.

And in addition to that, just within the last 2 weeks, we ran across an article that appeared, it turns out now, back in 1973. It is an article from Dr. Lou Harris's lab; he was in North Carolina then. And during the course of studies relating to pentazocine and a molecular weight protein called vasopressin, they gave animals Pyribenzamine, tripelennamine, in attempts to affect the lethality of pentazocine. And they found no effect.

Mr. NELLIS. Did you present this evidence to the drug advisory committee at the time the scheduling was considered?

Dr. SPEIR. No, sir, I did not, because I did not know about it. It only came to my knowledge about 2 weeks ago.

Mr. NELLIS. Did you present it to the committee after you found out about it?

Dr. SPEIR. It was just 10 days or 2 weeks ago I found out.

Mr. NELLIS. You are just hearing about it for the first time?

Dr. SPEIR. We are just hearing about it for the first time. The reference is in the bibliography I gave to the committee.

Mr. RAILSBACK. Would you yield?

Mr. NELLIS. I yield to Mr. Railsback.

Mr. RAILSBACK. May I just read you some information and ask you to comment as to its accuracy or reliability?

By the end of 1976, early 1977, referrals from the emergency room in Watkins for admissions were beginning to show considerable Talwin abuse, overdose, and addiction. The increase correlated with the first steady decrease of admissions for opiate abuse-talking now about the Northwestern drug dependence program.

Since August 1977, the central intake unit of Chicago drug abuse treatment programs has screened and processed more than 900 clients seeking treatment for Talwin abuse. This represents between 25 and 30 percent of the total number of new clients.

In the 1-year period April of 1977 to April 1978, there were 384 emergency room visits of this nature in the Chicago metropolitan area. I am wondering if you are taking issue regarding these figures as well.

Dr. SPEIR. No, sir; I have not had a chance to study those in detail, but I would not take issue with those on the basis of what I know now. I think there is no doubt there has been an increase, certainly in experimentation, with the combination, from what I can gather.

Mr. RAILSBACK. As I read this report-and I am sure we are further going to question some of the people that made this report-it seems, even forgetting the incidence of deaths which there may be and there may be a dispute as to the total number of deaths directly related to just the taking of Talwin, either in combination or without. But just these facts that I have cited, which come, I believe, from Dr. Alex Panio-but anyway, it seems to me that if these facts are accurate,