The Star Press from Muncie, Indiana • Page 11

Is Polio Show No Children Tests to Date III Effects oh Questions now on the minds of millions of parents, including thousands in Muncie and Delaware County, are answered below by an authority on the subject, Dr. Hart E. an Kiper, medical director of the National Foundation for Infantile Paralysis, who supervised research that led to development of the vaccine. Test vaccinations will be given to second grade pupils in the county during the week of April 18. Reprinted from U.S.

News and World Report, an independent weekly news magazine published at Washington. Copyright 1954 United States News Publishing Corporation. FY I Ell Lilly and Company, Indianapolis AN INITIAL PROCESS in the manufacture of the trial polio vaccine is the skinning and mincing of monkey kidneys to provide tissues for growing virus. The minced tissues'grow in a nutrient solution and then are seeded with one type of polio virus, which multiplies a million-fold and provides the material for the trial vaccine sponsored by the National Foundation for Infantile Paralysis. in Allegheny County.

We have not yet started any of the so-called field trials that will be under the auspices of the state health departments. Q. When do you expect to get those under way? A. Certainly, sometime in April. Because we have to be through before the polio -epidemic season starts, and we are doing it in schools and must get through it before the schools close.

Q. Would the fact that a polio epidemic occurs during the course of the program affect the results so that you have to terminate your tests? A. I don't think it would "affect the results of the test. It's just a question of if you had a lot of polio let's say you start in Dade County, Florida, on Monday and there were no polio but by Wednesday you began to have four or five cases. Well, it's a question of whether you stop or whether you go on.

Now, we all recognize that we are taking something of a calculated risk here, which you have to do with any scientific project such as this; and as you review incidence, there are not very many weeks that there aren't cases reported in some states. Just last week in going over the United States Public Health Service reports on poliomyelitis, I saw there were cases repotted in 24 of the 48 states. So, there's no time when you aren't going to have some around. Q. In the individual himself, if he had one shot and then were exposed to polio, would he then have enough protection to ward that polio off? A.

Dr. Salk seems to think and I think he is correct in his assumption. Last year, when he was giving the vaccine in Pittsburgh, he had taken blood from a number of children to determine whether or not they had any antibody to polio. He found they did not, and he gave them a dose of vaccine. Then in late May he had them all out to the clinic to give them their second dose, but there was enough polio around that he decided to discontinue his vaccine trials for the year at least for the summer but he did draw blood from a number of these children and found out that the vaccine had produced very little antibody.

And yet last Fall, in continuing his program, he took Wood again from, some of these children. He found that three children--who had had little antibody after this one dose of vaccine had somehow developed very high antibody to one strain. As he checked back, he determined that at least two of these three children had had very intimate contact with a case of paralytic polio in the summer- That showed they had immunized themselves. In other words, instead of getting a booster shot, they had been exposed to paralytic polio and had acquired their own immunity. Q.

How are you going to tell that the antibody produced, or the immunity produced, in the test children is the result of the vaccine and not the result of natural exposure? Are you measuring the antibody level before and after the three doses? A. We are doing that on about 2 percent of the total children in the study. In other words, for each 1,000 children who are vaccinated, samples of blood from 20 will be drawn before vaccination and then about two weeks after the third dose to find out what happened to their antibody. By doing that we'll find out several things. One, we'll find out what the level is in the community.

We find that some communities have apparently experienced repeated exposure to the virus and have a very high degree of immunity, and in other areas we find a very low immunity. So, we can measure the community immunity in terms of antibodies. Then, second, we'll find out actually what the vaccine did in creating antibodies in those children where there had been none at all. Q. Are there any places, wher the tests have been banned? A.

No. There've been various reports of that. But right in our Foundation for Infantile acute paralytic poliomyelitis, and actually died of the disease. Q. And there is no chance of that happening with this vaccine A.

No. Because in those early days they merely mixed formalin with virus which was not very pure. It was made from nervous tissue and contained a lot of animal 'protein. They added the formalin and let it inactivate while it was being shipped from the laboratories out to wherever they were going to use it. Today, on the other hand, the Salk vaccine is very carefully controlled in its production, and is subjected to every safety test before it is injected into any human being.

Q. How grown? is the current virus A. Until very recently, the only source of virus at all for any sort of laboratory work came from infected monkeys or cotton rats. You infected the animal, then later sacrificing it, removed its brain and spinal cord, and the virus was contained in that. But it is impossible even today to purify that mixture You always have- a considerable amount of nervous tissue in the mixture.

Now, the Salk-developed vaccine is grown in tissue that has a very, very minimum amount of any protein in it. Q. Where do you get this tissue? A. The basis for the tissue culture is monkey-kidney tissue. The kidneys are removed from a monkey and cut up into small bits and placed in flasks with a nutrient fluid.

Now, that fluid is a synthetic mixture that contains no animal proteins. Therefore, the only animal protein at all in the vaccine is the little amount that may come from the monkey kidney. Q. There's not enough of that to cause any adverse reaction? A. No.

The question has been raised about the matter of sensitizing human beings to monkey-kidney tissue. That question has been so carefully investigated that none of us believes that the small amount we must admit is present is sufficient to cause any sensitivity. Then, too, we have to remember that in one single course of vaccination, and in subsequent vaccinations, the total amount of tissue that would be injected into a human being is so small that we have no reason to believe it would 'cause any trouble. The actual investigation that has been done ha3 shown that it does not cause any trouble. Q.

How long will this vaccine protect against polio? A. Well, that's an answer that time, and time alone, can give. Q. is that the reason you are planning the tesljs among school children? A. No.

Actually, we're testing the vaccine to determine whether or not artificially produced anti- bodies will protect against paralytic polio. Q. What do you mean by antibodies? A. We all know that for every single infection to which man is ordinarily subject, at the time of that infection the body develops antibodies protective substances within the blood that are specific for each single disease. In this particular instance we're trying to find out whether or not this polio virus which has been killed and injected into humc beings will stimulate that individual to develop antibodies just though he had an active infection of live virus.

Q. And this is being done with school children, isn't it? How many of them? We anticipate that, altogether, some 750,000 to a million children will actually receive the vaccine in the course of the next few months. There are actually to be two types of study. In some states the children in the second grade, parents request that they participate in the study, will receive the vaccine, and the children in the first and third grades will be observed to determine whether or not there is more or less poliomyelitis office the letters were sent out to the state health officers asking their co-operation, and in not a single instance has a state indicated that they would not cooperate. Now, the state health officer can have great interest, but probably couldn't do anything if the local county health departments didn't decide to co-operate.

There are two ot three states that have simply said they will not designate trial vaccine areas until they have had certain additional information, and they are perfectly entitled to do that. But there aren't any of them that have flatly refused to enter the study. Q. What additional Information do they need? A. Some of them have scientific advisory committees, and thes committees want to have more information about, let's say, the kidney sensitivity.

They want to ba assured that the commercially produced vaccine is equally antigenic, that is, good in producing antibodies. And that is why Dr. Salk is still going to study about 2,500 children that he vaccinates with a commercial vaccine to see what their response is as compared with the vaccine that he, himself, makes in his laboratory. Q. Haven't there been some medical experts who have made the comment that this vaccine isn't ready yet for such a test? What do they mean by that? A.

Everyone has his own pet theory. There are those who feel we can't expect to get as much immunity from this killed virus as we could from the so-called attenuated, or tamed, virus. In other words, they want to wait. On the other hand, we feel and I believe the majority of the scientists in this country feel that polio constitutes such a problem that if we have a vaccine which apparently will protect, let's find out if it really will. If it does, then we can go on to improving the vaccine, just as other biologicals have been improved as time goes on.

Sure, we could wait five years and get a better vaccine. But aren't the 30.000 polio cases a year that we may prevent worth putting on the test now? Q. What about this "killed" virus versus "live" virus? And what do you mean by "tamed" virus? A. We know that there are certain polio viruses that cause a higher percentage of paralysis than others. That doesn't necessarily mean type 1, 2 or 3, but there are some strains of these types that do.

Now, these viruses can be attenuated, or changed, in various ways. The yellow-fever virus, of course, was tamed by growing it in an em-bryonated egg. In passing it from egg to egg to egg, the virus lost its ability to cause yellow fever in man, and yet that virus was able to produce in man a good immunity. So, that's what you call "changing" the virus, that is, changing its characteristics in the case of polio, its characteristic to cause paralysis. Q.

Is the tamed virus more desirable from an injection standpoint than a killed virus? Is there less danger? A. Well, something that's dead can't cause disease; in something that has been tamed, there's always that chance that it might revert back to its earlier characteristics. As long as it is alive, it is always a potential danger unless it is completely changed. Q. Is there more of a risk from a tame virus's getting wild again or from a killed virus's not actually being dead? A.

I think we go back to this thing of how dead is dead. If you have absolutely killed the virus, you have nothing to worry about. It certainly can't come back to life Q. And that's the situation with the Salk vaccine A. That's The virus Is dead.

And once it's killed, then you don't have to worry about its causing paralytic disease. On the other hand, the attenuated or tame virus might revert back. Now, that doesn't mean that some day maybe this year, maybe next, maybe five years from now someone will not have effectively altered the characteristics of the polio virus that it can't possibly cause paralytic disease but can still stimulate the body to produce antibodies. Q. Is there any work going on In developing this tame virus? A.

Yes Dr. Sabin, in Cincinnati, is working very hard on this matter of taming or attenuat- ing the virus. Dr. Enders, in Boston, is also working on it. So is Dr.

Cox. at the Lederle Laboratories. They are all working on it 'In different ways, of course, but they are all working toward the same end. Q. Can a parent have his child tested to determine whether he has immunity to the various types of polio? A.

Yes, it can be done, 'but it has never bepn a very practical measure because, while knowing that your child was immune would give you great security, knowing that he wasn't immune, up to this time, would mean nothing because there was nothing you could do about it. I do anticipate that one of these days someone will develop a very simple test that anyone can run. If we have a vaccine and if we hava a test to determine immunity, then, of course, you would have to vaccinate only those individuals who were not already immune. Q. Should a parent haye his child tested before he decides whether or not to have him volunteer for this program? A.

There simply wouldn't be the time or the laboratory facilities to do that at this time. After all, we find a degree of immunity to all three strains of polio virus so infrequently that I would say it is certainly better to go ahead and allow your child to participate in the program rather than to go to the expense and trouble to determine his immunity at this time. 1 Photos Paralysis. from National Q. Is this new polio vaccine safe to take, Dr.

Van Riper? A. The matter of safety Is certainly one problem that I think should have been answered to everyone's satisfaction. Of course, there may be a few who will always raise questions, but we have to ask ourselves: What can be safer than safe? Each lot of this vaccine that is produced is subjected to three independent tests for safety by the manufacturer, by Dr. Salk's laboratory, end by the Laboratory of Biologies Control of the National Institutes of Health in the Public Health Service. Q.

Who Is Dr. Salk? A. Dr. Jonas E. Salk Is the individual who developed the vaccine.

He has taken many principles that havabeen developed in immunology and has combined them to the A DR. IIART E. VAN RIPER point where he has developed a method for taking poliomyelitis virus and inactivating it that is, killing it by treatment with chemicals. Q. Ton take live polio virus the virus that causes polio grow it, then kill it? A.

Yes. Perhaps the best way to describe, it is that we know there are three types of polio virus that cause paralytic disease in human beings. Q. Is that the reason you can -have polio more than one time? A. Yes.

Immunity to one type of polio virus confers no immunity to either of the other two. A strain ot each of the three types of virus is treated with formalin and then they are pooled in equal parts. After that the formalin is neutralized. The vaccine is then tested in the three laboratories. It is tested by a series of what we call "tissue cultures." Yoir take tissue that is growing in a tube, just like the tissue that is growing for the propagation of the virus, and then you put the vaccine in it.

Now, if there is live virus in there, it will grow in the tissue culture and destroy the cells. In addition to that, the vaccine is tested by injecting it directly into the brains of one group of monkeys and into the muscles of another group. Q. And this Is done in all three places A. Independently.yes.

The vaccine, before it can be used, must have been cleared by all three laboratories. In other words," there must have been no evidence of virus growth in any of the tissue- culture tubes. Q. What does the vaccine look like? A. It Is a perfectly clear liquid that is sort of pinkish in color.

Q. Hal It been given to any chil- drcn A. Oh, yes. Dr. Salk started, just about a year ago.

giving: it to a number of children in Pittsburgh and Allegheny County, Pennsylvania. Altogether Dr. Salk has given this vaccine to about 5,000 children. Q. Has there been any reaction? A.

There hasn't been any unfavorable reaction, either local or generalized, in any of the children, with one exception, and that was a child who was known to be sensitive to penicillin. Penicillin is added as a preservative to the vaccine. All vaccines that are made, that are to be stored for any length of time, have preservatives added to prevent the growth of the common, ordinary bacteria. Q. Does this mean that somebody who is sensitive to penicillin would have an adverse reaction to the vaccine A.

Well, all this child had was a little hives, or what we speak of as urticaria. It wasn't anything ot any moment. At the same time, Dr. Salk knows that there were a number of children whom he has vaccinated who have histories of penicillin sensitivity, and they had no trouble at all. Q.

Haven't vaccines been tried before for polio? A. Yes. It was in 1935. Q. Didn't some children die from that vaccine? A.

Unfortunately, there were soma youngsters who developed globulin to go around. There Is enough gamma globulin for about 1.9 million doses this summer and as I said before, there are about 45 million children who might very well be subject to epidemic situations. Q. So that gamma gobulin will continue to be used as a stop-can A. That's right-least.

-this summer, at Q. How many areas are involved in tests of the new vaccine? A. We hope that there will be at least one county, or an area, in every single state. Actually, the total number of areas is something under 200. Q.

Why were these areas chosen? A. They were chosen for various reasons. I think probably scientifically the geographic selection was done on the basis of getting a pretty good cross section of the socio-economic condition of all the nation. That is, polio is somewhat different in the South from what it is in the North Q. Is it a different disease? A.

No different social and economic groups are represented. Polio, you know, is not now a disease of the large cities. It's more a disease of the suburban or even the rural areas. Q. Why Is that? A.

The probability is that children growing up in cities are constantly living with and being exposed to the virus so that they develop an acquired immunity, and although they don't have the paralytic disease, they do have the immunity; whereas the child living in the rural areas has different living conditions generally and may have less contact with the virus, and thus less opportunity to develop immunity at an early age. Then, too, we've selected the counties for other considerations as well. A review of incidence of poliomyelitis definitely indicates that there are certain areas or counties where over the years their experience has shown a higher than average incidence of poliomyelitis, year in and year out Now, in this particular trial, of course, we want to pick the coun- ties where we are likely to have an epidemic, because it's only after, we've had an epidemic, or at least a sufficient number of cases, that we'll have an answer to whether this whole vaccine thing is any good at all. Q. Has this inoculation program already begun in these areas? A.

No. Dr. Salk has been carrying out his work only Mum In the vaccinated group than the uninoculated group. This is called "observed controls." In certain other states, children in the first, second and third grades will be asked to volunteer. They will all get an inoculation, but one half will receive an ineffective solution a dummy shot, or what some people call the placebo.

It's impossible for the physician giving the shot to know whether he's giving the child the polio vaccine or whether he's giving the child the ineffective substance. Q. How many shots does a child get? A. Three. The old principles of immunology apply in this business of polio just as they do in other diseases.

We know, for instance, that the child who has been immunizedlet's say, against diph- theria over a period of time loses his antibody. But with an additional or "booster" dose, or what they call a "recall" dose of diphtheria toxoid, you immediately get a tremendous response and a rise in antibody. Now, with poliomyelitis we are going to give three shots. The first two are given, let's say, to sensitize the body to produce antibodies, and the third dose is what we call the "booster" or "recall" dose. Q.

Is there any way that a parent whose child isn't in this age group can have his child inoculated? A. Not this year. That's because the amount of vaccine available before the polio season will be just sufficient to get, we hope, the number of children we need in the study to give us the answer as to whether the vaccine is as effective as we be-r lieve it will be. Q. When will you have, the answer? A.

We say we can't expect to get the answer much before early 1955. Now, if we should have very early epidemics of poliomyelitis in a number of these areas where we're doing the trials, and the epidemic is over in, say, October, then immediately the evaluators will get in there to determine what happened. We can't do that much earlier because as soon as you break the code, and they know which children got the vaccine and which got the placebo, you've destroyed the thing we've been trying to build up an impartial evaluation. Q. If the vaccine proves out, and you get the answer in early 1955, will the vaccine be available for the following polio season the summer after this one? A If the vaccine is sufficiently effective to warrant its continued use, I can't believe that there'd be enough vaccine available in the late winter and early spring of 1955 to give the vaccine to all those who might want it.

In other words, the potential market right now in the most susceptible age group is probably 45 million children, and X' A i that's a lot of vaccine when you figure 3 cubic centimeters for each child. Q. Would that give them lifetime immunity? A. We're not counting on it lasting that long at least now. Again, that's something that Dr.

Salk will have to do. He'll have to continue to check those children that he vaccinated about a year ago about 600 of them. The old science of immunology will help there because polio is like other diseases and we know we can calculate the rise and fall of antibodies in other diseases. Assuming it follows the same pattern in polio, then we can say that a child should be vaccinated in infancy and be given a booster "dose, perhaps, when he goes to school when he is five or six years of age and maybe a third booster dose in early adolescence, when he is going to high school. Dr.

Salk feels that that certainly would give a lifetime immunity. Q. With this vaccine apparently so promising, where does that leave gammaglobulin? A. Well, gamma globulin will still be. used this summer of 1954, certainly, because we are carrying on the vaccine program in something less than 200 counties and there are better than 3,000 counties in this country.

What we hope i3 that the gamma globulin will be used to cut down the incidence of paralytic poliomyelitis in those areas wherethe vaccine isn't being tried. Q. Where does the gamma globulin come from? A. Gamma globulin comes from human blood. The antibody is in the gamma globulin and is there because that individual has suffered an infection with poliomyelitis virus, whether he became paralytic or not.

But the gamma globulin just gives you a passive immunity that lasts from five to six weeks at the most, and the vaccine we know is effective for at least a year and have every reason to believe it will last much longer than that. Q. Wasn't there a committee that recently put out a report questioning the value of gamma globulin? A. Yes. That was the report that was made by the committee that met in Atlanta some weeks ago in which they evaluated the effect of gamma globulin when it was used in the summer of 1953.

They reported that there was apparently no effect with gamma globulin when used in intimate family con- tacts. That is as we predicted it would be, because no one had ever conducted any experiment that showed that it was of any value when used that way. Now, the experiment that Dr. Hammond of Pittsburgh conducted in '51 and '52 showed that when gamma globulin was given to large groups in communities what we called mass inoculations at the proper time and in the proper dos- age, it did result in the reduction of paralytic poliomyelitis. We know that poliomyelitis is what we call a family disease.

In other words, the more intimate the contact, the more likely the virus will spread within the family household. We also know from Dr. Hammond's experiment that, unless the gamma globulin is given at least prior to the time the individual acquires the virus, it has little, if any, effect. In other words, the virus in the body takes seven to 14 days to incubate, and if the incubation process is already going on, the gamma globulin isn't effective. Q.

Will it be allocated this year the same as last year? Isn't the supply very limited Well, we have about three times as much available this year, and by cutting out the waste of gamma globulin in family contacts and having it available just for the group immunization, we feel it can be used much earlier in the course of the epidemic, and the earlier it is used, the more effect we can expect from its use. Q. Should parents have a child get a shot of gamma globulin every six weeks? A. I would say it would be nice If he could, but he won't be able to because there isn't enough gamma Pittman-Moore, Indianapolis. ELABORATE SAFETY TESTS are carried out at every step in the commercial manufacture of the trial polio vaccine.

One of the final tests is made by inoculating the finished vaccine into test tubes containing animal tissues and nutrient solution No. 199. This medium is ideal for the growth of the virus. If any live viruses remain in the vac- cine, they will multiply and be quickly detected by microscopic examination of the tissue culture. This batch of vaccine would be discarded immediately.

After all safety tests have been passed, this vaccine would be ready for use in the validity test being carried out by the National Foundation for Infantile Paralysis. LITTLE FRANK SCAKPINO, age 8, receives trial. polio vaccine by Dr. Jonas Salk during polio vaccine trials held in Pittsburgh, Pa..