Rivers: If my memory doesn't play me false, Louis Weed, Joe Stokes, Howard Howe, and Lloyd Aycock all received grants which allowed them to pursue questions relating to the fundamental nature of the virus. But you are right when you imply that most of the research [END PAGE 182] funds went toward developing a vaccine. As a matter of fact, Dr. William H. Park received a great deal of money from the Birth-
day Ball Commission for just such a purpose.

.Q: Did the Rockefeller Institute get such help? After all, the Insti-
tute pioneered in the field of polio research in the United States.

Rivers: As I mentioned earlier, de Kruif and Flexner didn't get along, and it should come as no surprise, that the Institute didn't get any money from the Birthday Ball Commission. I doubt whether the Institute would have taken it even if it had been offered, first, because Mr. John D. Rockefeller, Jr., did not allow anyone from outside- either government or private agencies-at that time to contribute to the support of the Institute research projects, and, second, because Dr. Flexner did not think that it was possible to make a practical vaccine against polio at that time.
Paul de Kruif did know William H. Park and considered him a very distinguished scientist and one certainly worthy of support. Let me add that Dr. Park in his heyday was a great. He was an original and had made important contribution to our understanding of diphtheria, influenza, and measles. In the late twenties Park became interested in polio and tried to develop a horse serum against the disease. As might be suspected, the serum be developed didn't work. Park, and for that matter other workers at that time, didn't know that there were three types of polio, and even if the antiserum Dr. Park made in a horse had worked it would only have been good against one type of polio. Dr. Flexner was pretty acid about this work and I suppose part of it went  back to the fact that there was no love lost between the two men. Now what I am going to tell you is rumor, gossip, hearsay-call it what you will-but it was common talk among the bacteriologists of my day.  You may remember that I told you earlier that Flexner, Park, and Lewellys Barker in 1899 were part of a commission to investigate dysentery in the Philippine Islands. During the course of that expedi- tion, a new dysentery organism was discovered. The honor of that dis- covery went to Dr. Flexner and the organism was named after him. The story goes that Dr. Park always felt that he was the true discoverer [END PAGE 183] of the bacillus and that it should have been named after him. Now, I don't know who discovered the bacillus. I don't care to know if Flexner did or Park did. This was gossip that went the rounds and was used in explanation of why Flexner and Park were not friends.20

Be that as it may, I want to tell you that, if Dr. Park ever needed polio material for experimentation, he always sent to Dr. Flexner for virus, and his request was always filled and promptly. That was one of Dr. Flexner's attributes, and it still is one of the attributes of the Institute. If we have something at the Institute that other people want, other people usually get it.

In the early thirties Park teamed with a young Canadian bacteriologist named Maurice Brodie to produce a formalinized inactivated vaccine against polio. Dr. Brodie had trained at McGill. Early in 1930 he showed up at the Institute with a letter from one of his professors saying that he wished to learn about poliovirus. Dr. Flexner was very nice, took him to his laboratory, and turned him over to Peter Haselbauer. Peter is what I would call a very high-class technician. He came to the Institute when be was a young boy-just out of high school, I believe-and Dr. Flexner trained him as a technician. He spent his entire life at the Institute and became in fact Dr. Flexner's technician. He was associated with Dr. Flexner in polio research almost from the beginning of Dr. Flexner's own researches in 1909, and so he knew a great deal about the MV virus used at the Institute. Peter was a pretty smart hombre and, although he didn't have formal collegiate training, he was good. Flexner would write out the protocol for the experiment, and Peter would do it. Peter, of course, was in no position to form an opinion as to whether the old man was right or wrong about a given experiment, because he didn't [END PAGE 184] have the background, but, as I say, he was a superb technician and Flexner could rely on him. Peter taught Brodie about the MV virus for about a month or six weeks, and then Brodie returned to McGill. After that I didn't hear about Brodie for several years. Actually, I didn't hear of him again until he came to New York University as assistant professor of bacteriology in the Medical School and had joined forces with Dr. Park to try to produce an inactivated formalinized vaccine against polio.

At the time Dr. Brodie came to work with Dr. Park, Park was failing, and as a matter of fact he later became very senile. On several occasions Brodie came to see me at the Institute to discuss problems related to making an inactivated vaccine and while I listened to what be had to say I said little in reply, because I didn't want to hurt Dr. Park's feelings. In 1935 Brodie claimed that he had an inactivated formalinized vaccine that was capable of inducing immunity in monkeys and humans. Among other things, he maintained that he had developed a minimal completely paralyzing dose of virus. He carried out his titrations to five and six decimal places. Don't ask me how he got such titrations because I don't know. I do know that I didn't believe them. Later Brodie took a lot of people, bled them, and did antibody titers. Many adults, as you know, have antibodies against type 2 polio. Brodie claimed that, when he gave them formalinized suspensions of virus, he could demonstrate a rise in antibodies. Well, while the amount of stuff he injected might have acted to cause an increase of antibodies, I seriously doubt whether it could have induced the antibodies to come to the point where he could demonstrate them.21

Everything, as I say, came out just right, and Brodie and Park per- suaded public health officials in California to allow them to immunize about 7000 children with their vaccine. Dr. Ralph Muckenfuss who had earlier worked with me at the Rockefeller Institute, was at this time associated with Dr. Park, and he told me-and you might confirm my remarks with him to see if I have unintentionally distorted what I am about to say-that the vaccine was made in the most incredible sloppy manner. [END PAGE 185] The question we now come to is whether any of the children who received the Park-Brodie vaccine came down with polio as a result of using the vaccine. Dr. Norman Topping, who was with the U.S. Public Health Service in California at that time, has maintained that some of the children who received the Park-Brodie vaccine could have come down with polio as a result of the vaccine, because they came down within the proper incubation period after having received the vaccine. However this, as far as I know, has never been proved. It is unquestionable, however, that some of the children who received the Kolmer live-virus vaccine at that time did come down with polio.

Q: Dr. Rivers, in retrospect, there are a number of disquieting aspects to the Park-Brodie vaccine incident. Isn't it true that, long before immunization with the Park-Brodie vaccine took place in California, workers at the Rockefeller Institute were skeptical of Dr. Brodie's and Dr. Park's findings?

Rivers: That is true. Dr. Flexner was very skeptical of this work, and
I believe he asked Peter Olitsky to see if he could repeat Dr. Brodie's experiments. Dr. Olitsky, with the assistance of Dr. Albert Sabin and Dr. Perrin H. Long, then tried to see if they could immunize monkeys following Brodie's procedures and had no success at all. I watched them. They did a nice job, but they found it impossible to repeat Brodie's work.22 [END PAGE 186]

Q: If that is-true, why didn't the Institute make an attempt to halt the immunization program projected by Dr. Park and Dr. Brodie?

Rivers: Well, California is a long way from New York, and I expect that the people in California were much more cognizant of Dr. Park than they were of Dr. Flexner. Park's name was awfully well known the world over.

Q: Come now, Dr. Rivers, Dr. Flexner was surely as well known as Dr. Park. Even if what you say is true for California, how do you explain the fact that the U.S. Public Health Service allowed vaccination with the Park-Brodie vaccine in North Carolina and Virginia? They surely had as much respect for Dr. Flexner's name as for Dr. Park's name.

Rivers: Well, all I can say is, it's against the law to do many things, but the law winks when a reputable man wants to do a scientific experiment. For example, the criminal code of the City of New York holds that it is a felony to inject a person with infectious material. Well, I tested out live yellow fever vaccine right on my ward in the Rockefeller Hospital. It was no secret, and I assure you that the people in the New York City Department of Health knew that it was being done. Then again, the statutes of the City of New York plainly say, if there are cases of yellow fever in the city a yellow flag should be flown in the harbor for all to see. I don't know whether anyone
saw such a flag flying when I had several yellow fever cases on my
ward in 1931.

Unless the law winks occasionally, you have no progress in medicine. For instance, it was plainly against the law for people at the Sloan-Kettering Institute and the Memorial Hospital several years ago to inject people with what they thought were oncolytic viruses.   The Department of Health and the lawyers running the city knew about it but again they did nothing. They cooperated. Actually, you [END PAGE 187] have such laws to keep unprincipled people from taking advantage of
an unsuspecting public. Remember that Dr. Park, Dr. Brodie, and Dr. Kolmer were well-known scientists. For instance, John Kolmer's name was known all over the United States, because of the excellent book he had written on serological techniques. I don't think that there was a laboratory in the whole country that didn't make use of that book. They were not penny ante fellows.

Q: Dr. Rivers, apparently there were a number of people who did have second thoughts about both the Park-Brodie and Kolmer vaccines, Wasn't a meeting arranged by the American Public Health Association in October 1935 to discuss the safety of the Park-Brodie and Kolmer vaccines?23

Rivers: Indeed, there was such a meeting, and I was asked to go out
to Milwaukee and be the hatchetman. I kind of dreaded the job be-
cause I liked Dr. Park, but believe me I didn't mind jumping on Dr. Brodie and Dr. Kolmer. The meeting was much like any other meeting run by the Public Health Association. Brodie and Kolmer had been asked to prepare papers and I was asked to discuss them. While I remember the substance of my remarks, I don't remember the detail and I would like to submit here a typewritten copy of the remarks I prepared for that meeting. You can insert it later. I remember that there was subsequent discussion of my paper by Brodie, Park, and Kolmer, but I don't think that anything conclusive happened. After the meeting Dr. Foard MeGinnes asked me if I would join another symposium on poliomyelitis to be held at the meeting of the southern branch of the American Public Health Association in St. Louis the following month.24 This time I was asked to prepare a formal paper on immunity in virus diseases with particular reference to poliomyelitis. Dr. Brodie, Dr. Park, and Dr. Kolmer were again asked to prepare papers describing their work on polio immunization, and in addition Dr. Robert Onstott and Dr. Alexander Gilliam of the U.S. Public Health Service who were associated with field [END PAGE 188] studies of polio vaccination in North Carolina, were also asked to prepare papers.

The paper I presented was later published in the American Journal
of Public Health, and if, you examine it I think you will find that while I made more extensive remarks about the nature of immunization to virus diseases in general, the substance of my remarks about the Park-Brodie and Kolmer vaccines was the same as those I had made a month before.25 But I want to tell you that the meeting in St. Louis was very different from the one held in Milwaukee-the difference was James P. Leake of the U.S. Public Health Service. Dr. Leake was a very distinguished field officer who had had a long experience with polio, dating back to the epidemic of 1916. He was in charge of the immunization program in North Carolina and had followed very closely the polio cases that appeared after use of the Kolmer live-virus vaccine. Because Dr. Onstott and Dr. Gilliam were officially giving papers on behalf of the U.S. Public Health Service, Leake was not at the meeting in an official capacity. However, just as soon as I finished giving my paper (mine was the last in this particular session) and the floor was open to discussion, Leake was on his feet. I want to tell you, he was hot under the collar. He presented the clinical evidence to the effect that the Kolmer live-virus vaccine caused several deaths in children and then point-blank accused Kolmer of being a murderer.

All hell broke loose, and it seemed as if everybody was trying to talk at the same time. A little later Dr. Brodie got up and said, "It looks as though, according to Dr. Rivers, my vaccine is no good, and, according to Dr. Leake, Dr. Kolmer's is dangerous." He sat down and Dr. Kolmer got up. He didn't refer to me at all. He just said, "Gentlemen, this is one time I wish the floor would open up and swallow me." He then sat down.

Jimmy Leake used the strongest language that I have ever heard used at a scientific meeting and when he got through speaking both vaccines were dead. It took something like Jimmy Leake's statement to put an end to the vaccines. When you say somebody is committing murder, people usually stop and think. I believe that the vaccines would have died a natural death within a year, but Leake killed them [END PAGE 189] then and there-you didn't have to wait twenty-four hours. The vaccines were dead and so were careers. Within a very short period of time, Brodie was fired from his post at New York University, and Kolmer and Park retired.26 It was because of the Park-Brodie vaccine that I was asked to come on the advisory board of the Birthday Ball Commission.

Q: Could you explain the last statement a little more fully?

Rivers: Yes. Paul de Kruif and the rest of the boys on the Birthday Ball advisory board were afraid to tell Dr. Park that he couldn't get any more research funds. They had to have somebody like me-a roughneck-to get the job done. After I came on the commission, Dr. Park never got another cent. For the life of me, I couldn't see why he got all that money in the first place. I would have been in favor of giving some of those funds to Lloyd Aveock of the Harvard Medical School and David Kramer of the Long Island Medical School. Now that is not hindsight. Both Dr. Aycock and Dr. Kramer had had a long experience with polio through their association with the Harvard Infantile Paralysis Commission and knew polio from the clinical as well as experimental side. Aycock and Kramer ironically did receive some money from the Birthday Ball Commission, to test the results of the Park-Brodie vaccine immunizations in North Carolina. Later when the National Foundation came into existence, Dr. Kramer, who by that time had moved to the Department of Health of the state of Michigan, received several grants and did interesting work developing [END PAGE 190] a killed vaccine against polio. If I am not mistaken he got very sugges- tive results in mice but again no one took them very seriously.

Q: Dr. Rivers, live-virus and inactivated-virus vaccines were not the only ways thought of by doctors to protect against polio. Didn't some investigators like Dr. E. W. Schultz attempt to prevent infection through intranasal irrigations with various chemical agents such as tannic acid, zinc sulphate, and picric acid?27

Rivers: Dr. Schultz was not the only one who tried this. Peter Olitsky and Albert Sabin at the Institute tried it, and so did Charley Armstrong of the U.S. Public Health Service. I believe they all used different chemicals, but the general idea was to see if, by treating the olfactory nerves with chemical solutions, they could prevent the virus from traveling along the olfactory nerves to the brain. At that time Dr. Flexner thought that the virus traveled in lymph channels around the nerve to the brain but later -W. E. Le Gros Clark in England proved that it traveled along the nerves themselves.28 The experimental work with sprays in animals was suggestive, and in 1936 Dr. Armstrong tried using picric acid and alum sprays on children in Alabama. Armstrong was never able to prove whether the children whose noses he had sprayed were protected against polio. Actually, be never got a chance to run the controlled experiment he needed, because [END PAGE 191] parents in Alabama started to spray children on their own and the kids he did spray resisted so much the he never knew whether he had in fact thoroughly applied the spray in the nasal vault.

Later the spray idea was given an extended test in Toronto, and the doctors there concluded that the spray would not protect because you couldn't apply it properly without putting the child on his back and lowering his head in such a manner that he would. receive the full effect of the spray in the nose. It certainly wasn't a procedure that could be used for spraying large populations of children. Max Peet tried to devise a practical technique for spraying large groups of children but never came up with a practical solution. The sprays were not without danger-some of the people who received the spray lost their sense of smell. One such person was Dr. Donald Fraser of the Connaught Laboratories. He never regained it to the time he died. He told me once that the only objection he had to this loss was that he couldn't enjoy his sherry anymore. You know, you smell sherry instead of tasting it. Given these results, spraying of the nose with zinc sulphate, picric acid, or what have you fell into disuse. However, when the National Foundation came into being in 1938 people still spoke of sprays and the Foundation was quite prepared to support such a program if someone came up with a decent testing plan. No such plan was ever presented, and the sprays also died a natural death.

Q: Dr. Rivers, I still can't understand why the major research support of the Birthday Ball Commission was directed to problems of immunity, rather than dealing with basic problems relating to the poliovirus per se-for instance, trying to type the virus.

Rivers: I am not sure I understand all of this myself. You know, when the St. Louis encephalitis virus was discovered, in very short order it was differentiated from other encephalitis viruses like Japanese B, western equine, eastern equine, Venezuela, and so on. That never happened with poliovirus, largely, I believe, because, Dr. Flexner and Dr. Noguchi kind of overpowered people, even people, of great repute. While they never outright said so, they acted as if there were only one poliovirus, and if Noguchi and Flexner felt that there was only one poliovirus, why in hell should a young investigator just [END PAGE 192] out of Podunk question them and try to type viruses? I think this also held true for the question of portal of entry for the virus, although here I believe chance played a role as well.

Dr. Constantin Levaditi of the Pasteur Institute early claimed that
he could bring down monkeys by feeding them poliovirus by mouth.
Dr. Flexner, on the other hand, always disputed those findings because he couldn't infect his monkeys using this technique, although he could infect them readily enough by dropping the virus into the nose. Dr. Flexner worked with the Macacus rhesus, and he was absolutely right-you can't bring the rhesus down by feeding it virus. Levaditi on the other hand was working with the cynomolgous monkey, which can be brought down by feeding. If Flexner had Used the cynomolgous in his experiments,29 he would have found out that the monkey can be brought down by feeding. It so happens that the mouth is the portal of entry for the poliovirus in humans. I don't know many years were used up in debating whether the portal of entry was the nose or mouth. Progress was held up purely by chance because a big man like Flexner was using the rhesus monkey. If Flexner had used the cynomolgous monkey, the chances are that we might have had a vaccine that much sooner.

Q: Dr. Rivers, how would you characterize the research accomplishments of -the President's Birthday Ball Commission?

Rivers: Minus If you take the good things that they did, and subtract the bad things that they did, you get a minus. It doesn't mean that everything they did was rotten or useless. It means that when you add and subtract you get a minus. That's all. [END PAGE 193]

20 There is no doubt that there was a great antipathy between Dr. Park and Dr. Flexner. In this respect, what Dr. Rivers says above is true. The reasons that Rivers ascribes for that antipathy are, however, a complete myth. Dr. Park was not a member of the Philippine expedition, and there was never any debate between Dr. Flexner and Dr. Park over the discovery of Shigella flexneri. The bad feeling between the two scientists stemmed from Dr. Park's public attack on the efficacy of Dr. Flexner's serum treatment of meningitis before the Harlem Medical Society and in the public press (see New York Evening Post, January 16, 1912). Later when Dr. Flexner's treatment was proved effective, Dr. Park took the position that Dr. Flexner had merely copied the ideas of the German physician, Dr. Georg Jochmann (see correspondence in folder marked Meningitis Serum, Flexner papers). The myth here created is, however, revealing of Rivers.
21On this particular point, see also M. Schaffer and R. S. Muckenfuss, Experimental Poliomyelitis, The National Foundation, New York, 1940, pp. 80-82.
22Dr. Olitsky disputes Rivers here.
Dr. Rivers' memory is somewhat dim here. What happened was that I had started in 1935 on this work of reexamination of Kolmer and Brodie's experiments, employing ricinoleate (Kolmer) and formalin (Brodie) as virucidal agents, adding tannin for control and untreated virus (infected monkey brain) as another control to note whether an effective vaccine could thereby be produced for use in monkeys. I later requested my associate, Herald Cox (Drs. Sabin and Long Were not available then) to join me in this work. I had great respect for his ability and skill and desired to continue work on the polio problem.
The virucidal agents were used in the dosages prescribed by Kolmer and Brodie. We found that, in general, if these chemicals did not act a sufficient time, the vaccine by itself could produce polio in monkeys; it they were applied over longer periods of time and killed the virus, no immunity, except rarely, was induced to a test dose of virus given into the brain of vaccinees, but antibody could be found in the blood. Also, it was difficult to find an end point for formalin; ricinoleate was generally ineffective. Dr. Cox did well in this Work and this was the beginning of his researches on polio, which he continued after his departure from my laboratory with brilliant success (private communication).
For further detail of this work, see P. K. Olitsky and H. R. Cox, "Experiments on active immunization against experimental poliomyelitis," J. Exptl. Med., vol. 63:109 (1936).
23Meeting of the American Public Health Association, Milwaukee, Wisconsin, October 8, 1935.
24Dr. Rivers' reference here is to the Fourth Annual Meeting of the Southern Branch of the American Public Health Association, held on November 19, 1935, in St. Louis.
25 T. M. Rivers, "Immunity in virus diseases with particular reference to poliomyelitis." Amer. J. Public Health, vol. 26:136 (1936).
26The printed record of the discussion at this meeting in the American journal of Public Health does not contain the harsh language that Rivers claims was used by Leake. Here Leake is pictured as saying, "I beg you, Dr. Kolmer, to desist from the human use of this vaccine." It is very probable, however, that Leake used stronger language, and the editor of the American journal of Public Health later altered it for purposes of publication. Soon after my interviews with Rivers I had occasion to.speak with Leake about this point, and he told me that, while he didn't remember the exact words he used at the meeting, he did remember that he bad used some very harsh language. Cf. "Discussion of poliomyelitis papers," Amer. J. Public Health 26:148 (1936).
Rivers' account in one respect misconveys the outcome of the failure of the vaccines. The burden for that failure was publicly borne by Dr. Brodie. Dr. Park was retired with honors, Dr. Kolmer continued a useful and productive career as a professor of medicine at Temple University School of Medicine until his retirement in 1957. Only Brodie was fired and disgraced.
27Tne interviewer here was not as precise as he might have been in posing the question. There is no doubt that as early as 1934 Peter Olitsky and Herald Cox had demonstrated that a dilute tannic acid solution put into the nostrils of white mice served to protect them transiently against an intranasal installation of equine encephalitis virus. Subsequently this technique was independently and almost simultaneously adopted by Charles Armstrong, Edwin Schultz and Peter Olitsky in their experimental poliomyelitis research. See P. K. Olitsky and H. R. Cox, Science, vol. 80:566 (1934); C. A. Armstrong and W. T. Harrison, "Prevention of intranasally inoculated poliomyelitis of Monkeys by the installation of alum into the nostrils," Public Health Rept., vol. 50:725 (1935); E. W. Schultz and L.P.Gebhardt, "Prevention of intranasally inoculated poliomyelitis in monkeys by previous intranasal irrigation of chemical agents," Proo. Soc. Exptl. Biol. Med., vol. 34:133 (1936); A. B. Sabin, P. K. Olitsky, and H. R. Cox, "Protective action of certain chemicals against infection of monkeys' infection of monkeys with nasally instilled poliomyelitis virus," Abstract, 1. Bacteriol., vol. 31:3 5 (1936); article later printed in full, J. Exptl. Med., vol. 63:877 (1936).
28 Rivers has reference here to W. E. Le Gros Clark, Anatomical Investigation into the Routes by Which Infections May Pass from Nasal Cavities into the Brain. Ministry of Health Reports on Public Health and Medical Subjects, No. 54 H. M. Stationery Office, London, 1929.
29Rivers overlooks here that, soon after Dr. Flexner learned that Dr. Levaditi in co- operation with Carl Kling had reported experimental infection of cynomolgous monkeys by the feeding of poliovirus, he undertook to restudy the whole question of the mode of infection. The particular feeding experiments he undertook were not successful, and he concluded that the gastrointestinal tract played no considerable part as a portal of entry of the virus in man or monkey. See the report of Simon Flexner to the Board of Scientific Directors of the Rockefeller Institute, 1932, and S. Flexner, "Respiratory vs. gastro- intestinal infection in poliomyelitis," J. Exptl. Med., vol. 63:209 (1936).