CHAPTER XI

_IMMUNIZING WITH POLLEN EXTRACT_

The idea of preventing disease and poisoning by preparing the body with minute doses of that poison, gradually increasing until the body is immune, is an ancient one. The practice is Ur-alt, as my favorite German history books say; for it has been found among savages and primitive peoples and is practised in a crude way by every boy who accustoms himself to that noxious weed, tobacco. Then, there are the Psylli, whom Lucan tells of, who were by heredity immune to snake poison and who could make the favored stranger immune by inoculating him with small doses (_Pharsalia_, Book ix); and old King Mithridates, of Pontus, who believed in preparedness and kept himself prepared for the attentions of his faithful subjects by taking small doses of poison every day, keeping himself immune should by any accident some poison slip into his porridge (_Pliny_, Book xxv). Old King Mithridates was a good immunologist. He knew the transient nature of immunity and kept the treatment up. He knew that, if he stopped taking the poison for a week or so, he would go into a state of anaphylaxis and the next dose would kill him; so he kept himself in a state of anti-anaphylaxis by not permitting too long a time to elapse between doses, after the most approved rules of modern immunology. That patient whom Goodale immunized against horse-asthma who objected to a treatment that had to be taken for the rest of her life, should learn of old King Mithridates the true practice of immunity.

This is still the weak point of artificial immunity; it does not last very long. You can immunize a guinea-pig or a patient to almost anything now-a-days by giving him minute doses gradually increased but the immunity passes off quite rapidly when the treatment is stopped. We have still something to learn from Nature in this respect. Nature can give us one dose of yellow-fever or scarlet-fever or small-pox or measles and make us immune for life but your artificially produced immunity may last for a few weeks or months only. Our closest imitation of natural immunity is vaccination against small-pox. Here we produce an actual disease, cow-pox; yet, even here, we are not at all sure how long immunity lasts. Even in Jenner's time, the original belief in protection for life came down to seven years and our modern health boards would vaccinate every two years or, in the presence of an epidemic, more frequently.

However, Nature is a wasteful worker, wasteful of her material, and she kills a great many of her children with measles and scarlet-fever and small-pox and yellow-fever while immunizing the lucky ones. A Health Board that would kill so many people while immunizing the rest would be a public scandal. Yet it is probable that Nature's way is the most effective and that the best immunizer is the disease itself, as Koch found with tuberculosis among his guinea-pigs that the best protection against tuberculosis was inoculation with living tubercle bacilli, not with dead ones; and the autopsies show that the majority of the human race that grow up at all have been successfully immunized against tuberculosis by a mild local attack of the disease.

As yet, no one has had the boldness to inoculate human brings with living bacteria and to imitate Nature in her manner of killing off all the sensitive subjects in order to preserve the rest. This was formerly done by inoculation with small-pox but the unfortunate results of the practice compelled its abandonment among civilized people. Even Nature's immunity is not perfect in all diseases, as many a patient with his sixth attack of grippe or third pneumonia or fortieth year of hay fever has learned most feelingly; and this irregularity of natural immunity bears directly on the proposal to immunize patients against hay fever by small and increasing doses of the offending pollen. If the natural disease does not confer lasting immunity, you will have some difficulty in conferring lasting immunity artificially, as the immunologist is just now discovering. His immunity passes off so rapidly that he is now searching for a method of immunizing that can be carried on for many years without tying the patient to a laboratory for life. It is right here that I believe that homoeopathy has valuable methods that can be applied to the situation.

But we must not jump to conclusions. Because we can immunize successfully against one disease, it does not follow that the same methods will immunize against another disease. Each disease is a problem in itself and may require its own methods. Nor because we can immunize the guinea-pig in the laboratory, does it follow that the same methods are applicable in the human patient. The only proof that we can immunize against hay fever is to immunize against hay fever. So, to the subject!

=Passive Immunity.= The first man to attempt to apply the methods of modern immunity to hay fever was Dunbar, of Hamburg, in 1903, with this _pollantin_. He attempted to duplicate in hay fever the triumph of antitoxin in diphtheria by injecting a horse with increasing doses of pollen until the horse became immune to large doses of pollen and his blood full of antibodies. Dunbar expected to confer passive immunity on the hay fever patient by transferring to him this horse serum with its antibodies. There is no better example of the rule that each disease requires its own methods of immunity. While diphtheria antitoxin is harmless to the diphtheria patient, the serum of the pollen-immunized horse nearly killed the first patient Dunbar tried it on, who happened to be his assistant, a sufferer from hay fever. It is probable that pollantin is based on the wrong principle, that hay fever is not, like diphtheria, a poisoning by a toxin to be antidoted by an antitoxin. However, to Dunbar belongs the credit of first attempting to put the treatment of hay fever on a scientific basis and he introduced the method of testing the patient that has been followed by all later workers, dropping the pollen extract in the eye.

In the _Centralblatt für Bakteriologie, Referate_, xxxvi, s. 453, there is an account of a most unseemly quarrel between Dunbar and Weichardt, the latter claiming that before leaving Hamburg, he suggested the idea of pollantin to Dunbar. Weichardt has since put on the market another hay fever specific, called _graminol_, which is the blood-serum of cattle that have fed on the offending grasses during the hay fever season. The theory is that the blood of the cow contains antibodies to those grasses and that passive immunity can be conferred on the hay fever patient by transferring those antibodies to his blood.

This is the old, old experiment that has been tried so many times in many diseases and has so often failed. It reminds us of the many attempts to confer on the tuberculosis patient the natural immunity possessed by the jackass by injecting the patient with the blood serum of that friend of man. The result of these experiments left some doubt as to who merited most the name of jackass, the doctor, the patient or the patient beast. Both pollantin and graminol have been praised highly in Germany but neither of them have succeeded so well in this country. Perhaps a shrewd advertising campaign had something to do with it; for the combination of a German scientist and his manufacturer can give points to any Yankee in exploiting the public with sure cures for the sick.

=Active Immunity.= In active immunization, the real pioneers, after Mithridates, were the homoeopaths, who, for many years, have given small doses of poison ivy to prevent ivy poisoning and small doses of the poisons of infectious diseases to prevent and cure those diseases; but the homoeopath did not realize the transient nature of immunity and the necessity for continuing the treatment for many months or years, nor did he adopt the principle of increasing the dose to the point of toleration.

The first to attempt active immunization and cure of hay fever by injecting extracts of the pollen that causes the disease appears to have been Noon, working in Wright's laboratory in London. The work was continued by Freeman, their work being reported in the _Lancet_, 1911, i, page 1572 and ii, page 814. They found the English spring form of hay fever due to the pollen of grasses. By dropping extracts of various pollens into the patient's eye, after the manner of Dunbar, they concluded that their patients were most sensitive to timothy grass and they used timothy extract exclusively in the treatment. Freeman states explicitly that a patient immunized against timothy grass is immune to all other grasses of that season; that it is unnecessary to immunize him to each particular grass, thus differing from some of our American observers who use the skin reaction to determine the particular pollens to which the patient is sensitive and inject every one of those pollens in the treatment.

Independently of these British observers, Karl Koessler, of Chicago, in 1910, attempted to immunize patients against hay fever by injecting pollen extracts. Like Noon and Freeman, he used the eye reaction to test his patients and found them most sensitive to rag weed. Just as the Englishmen had used only timothy grass in their cases, Koessler used rag weed exclusively. His work is reported in his article on Hay Fever in Forchheimer's _Therapeusis_, Volume V and also in the _Illinois Medical Journal_, 1914, page 120.

=Selecting the Pollen. The Skin Reaction.= The next step in the development of the pollen treatment was to substitute the skin reaction for the eye reaction in testing the patient's sensitiveness to various pollens. The advantage of the skin reaction over the eye reaction is that it permits testing many pollens at the same time and does not distress the patient as does a sharp eye reaction.

While Noon and Freeman selected the one typical pollen of spring, the timothy grass pollen, and Koessler selected the typical fall pollen of the American hay fever, rag weed, for all cases of that season, later workers, using the skin reaction, go to the extreme of injecting the patient with each and every pollen to which his skin reacts. Oppenheimer and Gottlieb carry this individualization to the point of attempting to discriminate by the skin test the patient's varying resistance to his different pollens at each treatment. This resistance may rise for some and fall for other pollens so that six or eight different pollens in different doses must be injected separately at each treatment. This is individualizing the case with a vengeance and requires an expenditure of time and skill (I almost said _skin_) that must be rather expensive for the patient.

A series of light scratches are made on the skin of the forearm or the inner side of the arm where the skin is delicate. The scratch must be only superficial and not draw blood. Really the best method is to make a round denuded spot by twirling a small brad-awl. A drop of extract of different pollens or a speck of the pure pollen protein is rubbed into each scratch and the result awaited for fifteen minutes. Within that time, a redness and swelling, like a hive or a bite, will appear at some of the scratches.

This swelling is the skin reaction to that pollen. Its appearance indicates the presence in the skin of reaction bodies to that pollen. It is argued, and partially proved by practice, that the pollens to which the skin reacts are the pollens to which that patient has been sensitized and these pollens are selected for administration.

=The Dose.= The first dose of pollen extract is the danger dose and differs for each patient according to his susceptibility for a given pollen. It is determined by dropping the pollen extract into the eye or rubbing it on the skin. To avoid anaphylactic shock, this dose must be incredibly small. Noon and Freeman's first dose was one-third c. c. of the weakest dilution of which one drop in the eye would cause hyperaemia. This was usually four drops of a millionfold dilution in water. Later doses were never more than 1 c. c. of a 1 to 100,000 dilution "to avoid unpleasant reactions."

Goodale begins with five drops of that dilution that just fails to cause a skin reaction. Later, to avoid the risk of shock, he advises one-tenth of this dose.

Koessler's theoretical initial dose of rag weed extract is one drop of the weakest dilution that will just redden the conjunctiva. As he finds rag weed more toxic than the English timothy, his actual first dose is one-half of this theoretical dose. The actual first dose will vary from one drop of a 1 to 1,000,000 to one drop of a 1 to 20,000 dilution, the smaller of which he estimates to contain of pollen protein one one-hundredth part of a millionth of a gramme or .000,000,01 gramme.

Shade of Samuel Hahnemann, the first and greatest homoeopath! And they drove you out of Leipzig into poverty and exile for teaching that in using drugs that are similar to the disease there is serious danger of aggravating the disease; that the dose must be extremely small; and that disease so sensitized the patient that a dose so small as to be inappreciable in health becomes active in disease!

The smaller doses of pollen extract are given every three or four days and increased as rapidly as possible, judging the increasing tolerance or resistance by a diminishing eye or skin reaction. With larger doses, the interval is longer, a week or ten days. The pioneer, Noon, and all workers since, warn against increasing the dose too fast, for the reactive power of the patient is easily exhausted, his resistance lowered and he may be left more sensitive than before.

=Dangers of Pollen Injections.= Treatment by pollen injection is beset with dangers for the unlucky patient. It has been noted how Dunbar nearly killed his first patient by injecting the serum of the horse that had been immunized to pollen. All experimenters, without exception, say that the injection of pollen extract is attended with danger to the patient, danger of anaphylactic shock, and warn against the use of any but the most infinitesimal doses. The hay fever patient is a human being who, in some way, has been sensitized to pollen. He is in a state of exquisite anaphylaxis and a dose of pollen injected into his blood may kill him in twenty minutes. Goodale reports shock (faintness, nausea, vomiting) in two patients following the mere rubbing of a drop of pollen extract into a scratch on the skin. Evidently the scratch was too deep and the pollen poison was absorbed rapidly into the blood instead of being stopped by the deep epithelia. I have seen a similar absorption and general reaction in children after a skin test with tuberculin, when the tuberculin entered the blood through too deep a scratch.

Another danger lies in the instability of the pollen extracts. Koessler expressly warns against commercial preparations of pollen protein because of the danger of decomposition. His extracts do not keep more than three weeks and are dangerous to use after that time. On the other hand, Goodale, making his extracts with 15% alcohol, reports them as active and fit for use after more than one year. Oppenheimer and Gottlieb object to commercial preparations on different grounds. The commercial preparations contain many different pollens so as to be sure to include those to which the patient is sensitive. They point out that in these mixtures, the dose of the individual pollens cannot be adjusted to the changing conditions of the patient and, in addition, injecting into the blood of the patient pollens to which he is not already sensitive may sensitize him to these pollens also and leave him worse than before.

There is the lesser danger that the patient will not be immunized by the injections but become more sensitive to his old pollens than he was before, as Noon pointed out in his first paper; for artificial immunity is a difficult thing to control and is by no means as easy as it looks in the book. Nor is it as easy to immunize a human being over many years of life, subject to so many conflicting influences, as it is to immunize a guinea-pig living in a cage.

To lessen the dangers and enable the patient to keep up his immunization for many months and years, Goodale borrowed an idea from Schloss, who fed his egg-oat-meal-almond anaphylaxis patient minute doses of these foods until he so raised his resistance that he was able to eat them in ordinary quantities without harm. Such artificial resistance must be kept up by eating a small quantity of the food each day or it will be lost (old King Mithridates again). As most of the pollens are not edible and as patients react to botanically allied plants, Goodale tried feeding the patient over long periods of time with vegetables and edible plants that were allied to the offending pollens, expecting that, as in Schloss's patient, some minute part of the protein would pass unto the blood unchanged and maintain the protection. So far, these feeding experiments have failed. Trial with homoeopathically potentized pollens over long periods of time has not been made.

=Conclusions on Pollen Extracts.= My conclusions on the pollen treatment are that it is in line with our best practice of immunity but that it is still in an experimental stage, the pollens are possibly dangerous even in the hands of a skilled immunologist. In a disease that is usually so easily controlled by rosin-weed, faradism and ichthyol, I would not expose a hay fever patient to the very real danger of anaphylactic shock. The conditions governing immunity stated in the beginning of this chapter still hold good. It is transient. Already some of the early workers have discontinued the practice. The despair of Goodale has been quoted. Scheppegrell, probably the first in this country to use the pollens, has given them up and advises the patient to keep away from his irritant and to have the weeds cut in all cities as the best treatment obtainable (_Journal of the A. M. A._, March 4, 1916, page 710). The most hopeful aspect of the pollen extracts seems to me to be their administration all around the year in high dilutions, _more homoeopathico_, and to this practice I believe the immunologist will eventually come.

=Pollen Extracts not Vaccines.= Some manufacturers and all British writers speak of pollen extracts as _vaccines_ and of immunizing the patient as _vaccination_. This seems an unnecessary confusion. We have two kinds of vaccines already, the cow-pox vaccine and the killed cultures of bacteria introduced by Wright. For an account of the use of these vaccines in hay fever, we will pass to the next chapter.