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The basic reason for an organized attempt to solve the problem of preventing infantile paralysis lies in the simple fact that infantile paralysis is a disease which can be transmitted to experimental animals in the laboratory, and propagated in these animals under complete control of the investigators. To that extent infantile paralysis is not a mystery. While the human and monkey disease presents certain differences, yet, thus trapped in experimental animals, the various mysteries of the human affliction should be cleared up, given the qualified searchers armed with time and adequate facilities for the fight.

At the time the various scientific men, working under the Commission's grants, began their activities, two key questions dominated the thoughts and plans of all those interested: (1) Since it is an undisputed fact that infantile paralysis is an infectious disease, can experimental animals be protected against attack by the infantile paralysis virus? (2) If they can be so protected, will the means of protection be safe and simple enough to test in the field against the epidemics that every year threaten our children?

The fact of such a vaccine, able to guard experimental animals, had hardly begun to be questioned. Yet, even so, reputable scientists among our grantees questioned the rationality of such an attempt. After all, said they, in any epidemic, infantile paralysis attacks relatively few children in a given community. Would it not be wasteful in the extreme to try to vaccinate all children, those naturally immune as well as those susceptible? Would not the small number of children who, vaccinated or not, would contract the disease, make conclusions as to the vaccine's power questionable, if not valueless?

For some reason entirely mysterious, the bulk of children -- even early in their lives -- are naturally immune to this plague. But how can you put your finger upon the endangered child, so as to give only that one your hoped-for preventive? This is one of the major mysteries of the illness. There was no known test to reveal the threatened ones. Research to find such a test was urgently demanded.

Why is it, again, that among all human beings who are candidates for this fate of paralysis or death, the majority are to be found among the younger children? And what is it that causes more and more children to become spontaneously immune, as they grow older?

The majority of human beings have in their blood a peculiar protective power against the virus of infantile paralysis. This immune power of blood is demonstrated by mixing the virus of the disease with a sample of blood under investigation. It the blood is "immune," then the mixture will not be able to paralyze monkeys when it is injected directly into their brains. The mechanism of this defense is absolutely unknown. The immune substance, or power, appears in the blood of the bulk of people naturally, spontaneously, without their having to pay for it by undergoing an attack of the illness that is clinically detectable. But does any means exist of conferring this immunity of blood upon all children, all people, who are found not to have it?

The advocates of the proposed vaccine asserted that this could indeed be accomplished in the majority of people. But the question then arose: is this power of human blood against the infantile paralysis virus the real reason why the bulk of people resist the malady? The answer was by no means certain. There already existed facts hinting that infantile paralysis is uniquely and exclusively a sickness of our nerve tissues. It was by no means certain that this disease-fighting power of blood could penetrate to people's brains or spinal cords. Then, what good would the creation of mere immunity in people's blood be, in an organized attempt at protection?

Since the virus of infantile paralysis is, entirely beyond the reach of the most powerful microscope, it is extremely difficult to determine how it spreads from one child to another. Is an actually sick child required to spread it to other children? If so, how long is such a child dangerous to others? Quarantine regulations say three weeks. But this rule is based upon scientific facts that are inadequate. Research is demanded to find ways to spot such dangerous children.

If, as seems probable, the malady may also be spread by perfectly healthy people, how are these to be detected? Plans were presented outlining experiments that might begin to find an answer to this important riddle. And such proposed experiments were closely tied up with preponderating scientific opinion -- based partly on fact, partly on theory -- as to the unseen trail the virus takes, in spreading from one person to another. It is the belief of the overwhelming majority of searchers that this trail is exclusively from the nose of an infected person or a carrier to the endings of the nerves of smell in the nose of the person susceptible.

It was necessary to prove this extremely important point beyond peradventure, yet there have been isolated small epidemics where milk has been incriminated. Might it be that, sometimes, the virus gets in by way of the mouth, stomach, intestines?

While these questions are all of them practical ones, all giving hope of ultimate answers if money for really adequate laboratory and field tests were provided, yet it was important to support researches seemingly entirely academic, not immediately practicable. Exactly what, for example, is this infantile paralysis virus? Entirely sub-visible, true. But may it not be possible to determine its exact chemistry? Other viruses, such as that of the tobacco mosaic disease, are now believed not to be microbes at all, but curiously changed proteins, giant chemical molecules that come from the tissues of the tobacco plant itself, changed in some way so as to become murderous to healthy tobacco plants.

Might not the infantile paralysis virus be only some mysteriously altered nerve tissue of human beings? Should not, therefore, a serious chemical attempt be made to purify, to refine, to determine the chemistry of this virus? So that its true origin might be determined and, maybe, controlled and suppressed by chemical means?

Finally, a group of searchers from one of the greatest of all American medical schools brought forward plans for an investigation, seemingly theoretical, which past two or three years has turned out to be the most immediately practical questions demanding and answer. Is infantile paralysis ever found in any part of the human body -- excepting the nervous tissues? Is this the Achilles heel of the virus: that it can only live, multiply, in a child's nerves, brain, spinal cord? Can it sneak into the doomed child only by way of certain exposed nerves? Does it leave sick children only by this pathway?

Although the urgency of answering all these various questions has long been known, one reason why they have remained so long unanswered is the unparalleled costliness of infantile paralysis research. This is due to the unfortunate fact that the one experimental animal susceptible to this sickness is the monkey.

Now, the average cost of a monkey, year in and year out, is about eight dollars, and this has brought it about that most laboratories have been skimped for monkeys. Years of experiment and the time of scores of able investigators have been wasted, their results vitiated by conclusions drawn from experiments based upon an utterly inadequate number of animals. Diphtheria has been all but conquered, by the use of the inexpensive guinea-pig. Great strides have been made against pneumonia, because for the study of this ill there were countless mice costing ten cents each. But this happy state of affairs has existed for only a short period of years in infantile paralysis research. This was not because monkeys did not exist; they do exist in millions to the serious embarrassment of the population of India. But they cost eight dollars.

It was this situation that led the Committee's advisory medical committee to adhere to this basic aim: that no competent investigator should have in any way to stint himself in the matter of monkeys. For, if it takes a thousand mice to clear up a given pneumonia mystery, it may likewise require a thousand monkeys to answer a given infantile paralysis question. It is this possession of adequate experimental animals on the part of grantees that has led certain of them to their notable progress in the prevention of the experimental disease in monkeys now to be recounted.

It is inherent in the adventure of science that what appears a most promising project may fail disastrously when put to the test of human use; while at the same time most pessimistic theoretical conclusions may immediately precede, in fact bring into action, a research effort whose results give promise of practical test upon human beings. This is illustrated in the recent brilliant experimental results obtained by the Commission's grantee, Dr. E. W. Schultz, of Stanford University. Thanks to funds granted by the Commission, Dr. Schultz has demonstrated a safe and powerful preventive of infantile paralysis in monkeys. It must be stated that Dr. Schultz was preceded in this work by Drs. Charles Armstrong and W. T. Harrison of the U. S. Public Health Service, and to these latter belongs the priority. Yet Dr. Schultz's work began almost simultaneously, and proceeded independently of that of Armstrong and Harrison, though its announcement followed the first publication of the Public Health Service investigators. Schultz's first publication was also preceded by an investigation confirming Armstrong's, made by Sabin, Olitsky and Cox of the Rockefeller Institute.

Dr. Schultz's previous researches, together with those of workers in England and America, had convinced him that infantile paralysis is uniquely and peculiarly a disease of nerve tissues, both in monkeys and human beings. Hidden away inside of nerve cells, propagating itself inside these cells, the virus is safe from any immune power that might be conferred upon the blood of monkeys or children by vaccines; or from any immunity that might be introduced into the blood of monkeys or children, ready-made, by the injection of so-called immune blood serum. But if the infantile paralysis virus cannot invade the brain and spinal cord of a child to begin its nerve cell wrecking activity? According to the analysis of Armstrong, and also of the Commission's grantee, Schultz, the virus had one, and only one possible path of entry. That was by way of the delicate, hairlike endings of the nerves of smell, high up in the roof of the nose. These are the only nerve tissues in children (or monkeys) which lie uncovered, naked to the outside world.

It was an already known scientific fact that monkeys can readily be fatally infected with infantile paralysis simply by pouring the virus of this plague into their noses. Indeed, aside from injecting it directly into their brains, simple instillation of virus into their nostrils is the most certain way of giving monkeys the disease. Might there not be found, then, some simple, safe, chemical which, uniting with those hairlike endings of the nerves of smell, would block those nerves, shut them off from the attack of the infantile paralysis virus?

Pursuing the same line of reasoning and following the same trail preceding Schultz, and entirely independently of Schultz, Drs. Charles Armstrong and W. T. Harrison, of the Public Health Service, at this time published the fundamental fact that the nerves of smell of monkeys could actually be blockaded against the attack of infantile paralysis virus for a number of days. This could be accomplished by douching the noses of monkeys with solutions of alum or tannic acid. But these chemicals had a practical disadvantage, so far as their possible application of guarding children went, in that they were irritating, and in that their protective effect was a short one. Nevertheless, the principle was established that such a simple chemical prevention was possible, and credit for this must go to Drs. Armstrong and Harrison.

Now, at the same time, in the Winter of 1935-36, Armstrong in Washington and Schultz at Stanford -- one not aware of the work of the other -- discovered a far more powerful and at the same time less irritating chemical: picric acid. Three to six douches of picric acid were found to guard, for at least six days, nine out of ten monkeys from overwhelming inoculations of the infantile paralysis virus into their noses.

Here for the first time in history was a means by which experimental animals could be guarded by a preventive that was really powerful and not too dangerous to preclude its being tried as a preventive of epidemic infantile paralysis in children.

At this point the efforts of Drs. Armstrong and Harrison of the Public Health Service, and of Schultz working for the Commission, diverged. Armstrong further strengthened the preventive effect of his picric acid solution against monkey infantile paralysis by mixing with it a little alum. He then went into the field with this picric-alum preventive, to test its effect in the human epidemic that broke out in Alabama, Mississippi and Tennessee in the summer of 1936. Schultz confined his efforts to the laboratory: first, to determine the important practical point of how long this preventive effect of picric acid might last; and second, to try to find chemicals that might be still more powerful, even less irritating, and whose effectiveness might extend over months, instead of days.

During the autumn and winter of 1936, these researches of Schultz met with much success. Weak solutions of the very cheap and harmless chemical, zinc, sulphate, instilled, or better yet, simply sprayed into monkeys' noses, were discovered to confer almost 100 per cent protection of monkeys against overwhelming inoculations of otherwise fatal infantile paralysis virus, repeatedly poured into these animals' nostrils. Most important of all, this protection by harmless zinc sulphate turned out to be not a matter of a few days, evanescent, but of one to two months, at least.

It is thanks to Dr. Charles Armstrong, that certain important facts regarding the obstacles to, and the possibilities of, human application of this chemical blockade are already at hand. In the Southern epidemic of 1936, millions of doses of Armstrong's picric-alum preventive were sprayed into the nostrils of Southern citizens, young and old. The basic conclusions from this strange mass experiment by the masses themselves upon the masses are these:

(1) The procedure was essentially harmless. There were a large number of complaints of a minor nature, of headache, irritation, largely by older persons. There was no fatal or serious accident. (2) The mass of parents can be depended upon eagerly to welcome the introduction of any preventive offered them by competent and recognized medical and public health authority. (3) The mass itself, i. e., fathers and mothers, cannot be depended upon properly to apply the nasal spray, so that the endings of the nerves of smell of all children and grown-ups will be surely covered by the protective chemical. (4) In spite of the enormous variation in the skill and completeness with which the spraying was done by the largely uninstructed myriads, there is yet some evidence that, where the spray was applied sufficiently early in the epidemic, there resulted an apparent decrease of cases occurring.

Meanwhile the work continues, with a chance that some more simple, satisfactory method of completely covering the nerves of smell may be found. Is the zinc sulphate solution the last word in possible chemical preventives? By no means. And search for other ones is being diligently pursued.

Enormous time, energy and money have been wasted in many fields of medical science by the perpetuation of use of various erroneous remedies and alleged preventives not subjected to critical scrutiny of other workers. In short, it pays to find out what is not so as well as what is so. This, in the instance of the Park-Brodie vaccine, was done inside a year by various of the Commission's grantees. Brodie claimed that his formalinized vaccine protected monkeys against small but fatal doses of infantile paralysis virus.

This claim was definitely not substantiated by grantee Schultz, of Stanford University, and grantee Kramer, of Long Island Medical College.

Brodie claimed, further, that immunity could be shown to appear in monkey's blood as the result of the injection of this infantile paralysis vaccine but this claim was found to be exaggerated by check experiments by grantee Kramer.

It is not certain that the power of human blood against infantile paralysis virus is important in the protection of the human owner of that blood; but Brodie made the claim that the majority of not-immune children did acquire such power in their blood, after they had been injected with his vaccine.

But even this dubiously beneficial effect of the vaccine was not confirmed, when grantees Aycock of Harvard University, Schultz of Stanford, and Kramer of Long Island Medical College put it to test. Studying blood of children, vaccinated and not vaccinated in the 1935 North Carolina epidemic, Aycock found that, during the epidemic, virus-neutralizing substances appeared in about the same proportion of not vaccinated or vaccinated children.

Another vaccine, widely heralded in the summer of 1935, but not supported in its field trial by the Commission's funds, was apparently the cause of a number of tragic deaths of children who were supposed to be made immune with it. At the same time at least one fatal human case of infantile paralysis occurred in southern California at a suspicious interval after the injection of the Park-Brodie vaccine; and competent Public Health authority suggested that the vaccine may have been responsible.

Does this failure of the formaldehyde vaccine to protect children mean that all hope for infantile paralysis vaccination must be forever abandoned?

Not necessarily. Today, as this report is being written, word has been received from Dr. Kramer, of an entirely novel way of making monkeys immune. In brief, he has sprayed a harmless solution of Pituitran "S" mixed with adrephine, day after day, into the insides of monkeys' noses. This causes a notable mobilization of white blood cells to take place just under the mucous membrane, and around the endings of the nerves of smell of the monkeys. Now if, immediately after this spraying, Kramer sprays a fatal dose of infantile paralysis into such monkeys, these animals, a majority of them, resist this instillation! Then, when later tested, a majority of them are found actually to have become immune to the disease. This is, then, a sort of intranasal vaccination. It is not to be confused with the zinc sulphate or picric sprayings, because such sprays leave no permanent immunity. Kramer believes this experiment begins to explain, maybe, how in nature, the majority of children catch immunity, instead of infantile paralysis. For by this new method, immunity has been conferred upon a number of monkeys by way of their noses.

But that brings us to the heart of another one of the Commission's important projects. May it not be possible to discover a skin test, or a simple blood test, that would actually pick out the few susceptible children, out of a large population? If that could be done, then any effective vaccine, however expensive, would be at once a practical possibility. In short, will some test, like the Schick test, ever become available?

Grantee Dr. Joseph Stokes, Jr., of the University of Pennsylvania, is hard at work at the chemical "purification" of the infantile paralysis virus. That is to say, he is engaged in freeing this virus from the nerve tissue of the monkey, which is, at present, the one source from which experimenters can obtain it. The presence of this monkey nerve tissue would certainly "mask" and obscure any skin test that might be attempted on children. But if Stokes succeeds in his purification, some sort of test for the susceptible child might be hoped for.

Is there more than one virus of infantile paralysis? Grantee Dr. John F. Kessel, of the University of Southern California Medical School, has had an excellent opportunity to study this question during the epidemics of 1934-5-6 in southern California. At the very beginning of these outbreaks, it was plain that they were peculiar ones, and not typical infantile paralysis as it has for long been known in the East and in Europe. In southern California the disease was much milder. It did not paralyze people so severely, and their paralysis, when it did occur, was often not so severe, and the death rate in the epidemic was markedly lower.

Grantee Kessel was able to pass this peculiar infantile paralysis to monkeys, and propagate it in these animals. And he found that this mildness of the southern California virus was characteristic, too, of the disease in monkeys. Yet he has proved that this mild disease is surely infantile paralysis. For monkeys that have recovered only partly paralyzed, from this more gentle California type of the sickness, are, seventy per cent of them, now proof against the more savage virus of infantile paralysis of the East.

Two important practical possibilities arise from these observations of Grantee Kessel. Should the attempt to wipe out infantile paralysis by the chemical blockade of children's nerves of smell be found to have limitations, or to fail, it might then be necessary to fall back upon new attempts to vaccinate them. This might become feasible, if one or another of the Commission's grantees should develop a way to spot the susceptible human being -- which is not yet proven impossible. Would it not then be very valuable, in such a project, to possess a mild infantile paralysis virus? Just, as in the case of smallpox, people are not protected by that milder form of smallpox virus, vaccinia, which is obtained from cows?

Of course it is granted that, if the field trial of zinc sulphate or some other chemical, in the attempt to block the virus from getting into children, should be successful, then the question of whether there is more than one infantile paralysis virus becomes an academic one. In short, zinc sulphate wouldn't care which virus it prevented from entering. Yet, we do not know whether this science, so brilliantly successful in monkeys, will work for man. And it is common sense for us to have, experimentally, as many strings as possible to our bow.

This peculiarity of the Southern California virus has been confirmed in the important experiments of grantees Drs. John Paul and James D. Trask, of the Yale University Medical School. One of Trask's and Paul's viruses, obtained from Southern California, while it is not very fatal for monkeys, yet exhibits this ominous trait: that it can be easily passed from one monkey to another by simply injecting it into the skin of these animals. Should this hold, too, for human beings, with new viruses in future epidemics, what then would become of our now hopeful project to protect them by spraying chemical solutions into their noses?

A group of very able investigators at the Johns Hopkins University Medical School began a year ago last fall to strike at the very heart, so to speak, of the basic scientific mystery of infantile paralysis. And already a most significant preliminary report has been rendered by these workers. They are investigating from every known angle, bacteriological, chemical, anatomical, physiological, pathological, this most basic of all the purely scientific mysteries of the disease, namely:

Is it certain that the virus of infantile paralysis is able to invade, to multiply, to attack, and to destroy, the nerve tissues of human beings and monkeys, and their nerve tissues only? Their work answers this question in the affirmative.

From almost every laboratory during the past six years has come news that would make it seem as if this is so. Yet the old idea that infantile paralysis is first a blood disease and only later attacks nerve tissues dies hard. And it still has its proponents. Yet, the most hopeful immediate attack upon the key question of preventing infantile paralysis from invading children, rests upon the new doctrine that the virus of the sickness penetrates only by way of the nerves of smell, and can survive and multiply in, and attack, nerve cells and nerve cells alone.

One could not have been in intimate contact with the work described above, without acquiring a measure of enthusiasm and hopefulness which is perhaps too evident in this resumé of scientific facts. It I seem to have stressed unduly the advances made possible by the provision of needed funds, that is not to be taken to mean that all that results depend on is plenty of money. One reading this report should always remember that after all these scientists are still attempting solutions in many cases sought by them and their predecessors without success for a period as far back as seventy-five years.

All these problems are in good hands. Work upon them can only go forward when all keep to the belief that they can be solved despite past defeats. But this does not mean that all of the answers sought are bound to be found in a given time.