Pioneering Moderns In Hay Fever Research
( Originally Published 1943 )
Dr. William Scheppegrell Coming into the last leg of the hay fever road we meet many great men who started with modern hay fever in its infancy. A few of these men have actually grown up with hay fever developments. In this class is Dr. William Scheppegrell.
Dr. Scheppegrell may be considered to have been the bridge between early and modern hay fever researchers. More than this he has represented a bulwark of strength in the advancement of hay fever knowledge. His arrows of hay fever research were aimed in many directions. Most of them hit the target and left their mark. Although many of his endeavors were entirely without success he never once slackened his pace.
In I 908, with the early experimenters, Dr. Scheppegrell tried his hand at immunization. His method consisted of filling little bags with ragweed pollen flowers and instructing his patients to inhale the pollen dust. This procedure was to be carried out by his patients daily, for two to six weeks before the hay fever season. Favorable results were produced in some patients but not enough to warrant its continuation. Nothing was said of the painful results but we can just imagine. We forgave Dunbar so why not Scheppegrell.
Dr. Scheppegrell next centered his interest on the problems of plants and pollens as they are related to hay fever in the United States. Since the time of Blackley, Dr. Scheppegrell's work was the most extensive of its kind. Searching the fields he found ragweed to be the most prevalent hay fever plant in New Orleans. He conducted surveys and recommended campaigns for extermination of hay fever weeds. Through his crusading, weed ordinances were invoked in many cities. But none was ever successful in diminishing pollen concentrations in the large cities in which they were undertaken.
Another branch of his work consisted of exposing pollen slides and studying atmospheric concentrations in many localities. Coupled with the pollen counts he would study the hay fever plants in these and many other regions. This information was used as a basis by doctors for preparing appropriate extracts in particular localities. Through pollen slide study, Scheppegrell confirmed the information that the Mountain Cedar was causing hay fever in Texas during the winter.
Like Blackley, Dr. Scheppegrell was interested in pollen concentrations in the upper air. By means of slides ex-posed from airplanes he showed that pollen concentrations may remain uniform up to four thousand feet. He studied pollens under the microscope and reported on the size, shape, weight, and buoyancy of the various hay fever pollens. Through this work he proved that goldenrod was not an important hay fever plant because its pollen was too sticky and too heavy to be buoyant.
Dr. Scheppegrell wrote a good book on hay fever. In preparation for it he conducted many studies and obtained information on surveys pertaining to the nature of hay fever sufferers and hay fever incidence. In his book he reported the results of a survey on the prevalence of hay fever among the colored as compared to whites. He obtained data on social status and occupations of persons with hay fever. His findings indicated the erroneousness in the beliefs about hay fever being uncommon among negroes, farmers, and poorer classes. He presented statistics on the hereditary nature of hay fever; on its relative prevalence between the sexes and on the frequency of its occurrence at various ages.
The final section of the book contained an extensive list of hay fever resorts and comments about hay fever conditions in the various states, This information had been gathered through correspondence with State Boards of Health and other public officials. While we now recognize this as a very inadequate method of obtaining such data, it was a suggestion nevertheless.
With Dr. Scheppegrell's death in 1928 hay fever sufferers were deprived of an indefatigable ally who had devoted his life's work to the problem of hay fever relief. Fortunately for hay fever sufferers, during the last years of Scheppegrell's activity there appeared on the scene another investigator interested in the plant and pollen aspect of hay fever. At the time that Dr. Scheppegrell died, Oren C. Durham was still a novice at pollen research.
OREN C. DURHAM
Today, Oren C. Durham is regarded as the foremost authority in the field of botanical research related to hay fever. His name is by now familiar to the reader of this book. There are no impressive letters of the alphabet after the name of O. C. Durham. No degrees have been conferred upon Mr. Durham either honorary or otherwise. As we see it, this represents a sad commentary on the status of our educational hierarchy in the United States.
In order to obtain a college degree a man has to matriculate at a college, take about thirty-five courses, and write a few compositions regurgitating the information imparted by the professors for student digestion. The content of the thirty-five courses generally constitute the information in thirty-five textbooks, preferably those that the instructors in charge of the courses have written.
Mr. Durham has conducted original research pertaining to pollens, plants, molds, meteorology and aerobiology. He has written thirty-eight original papers and one book. In preparation for this he has probably read one thousand thirty-eight books. Mr. Durham has served as botanist for Abbott Laboratories for almost twenty years. He has acted as an assistant to those famous pioneers, Drs. Lowdermilk and Koessler. He has conducted research in collaboration with one of the best of the early pollen and plant re-searchers, Dr. W. W. Duke. More recently Mr. Durham has collaborated with such important allergists as Dr. Samuel Feinberg, Dr. J. H. Black, Dr. S. J. Parlato, and Dr. C. B. Sylvester. Mr. Durham is listed in Men of Science. However, no one has preferred him the honorary degree of Doctor of Science or even Bachelor of Science.
What are we waiting for? Are we going to repeat the experience of the famous entomologist, J. Henri Fabre who, upon receiving great honors when he was about ninety years old remarked, "They are giving me a cookie now, when I haven't any teeth with which to eat it."
Mr. Durham's contributions to hay fever advancement are truly inestimable. Oddly enough his name is unknown to more than half the doctors whose practice in hay fever therapy has been greatly influenced by his work. By his collection of accurate pollen data, accompanied by careful field studies in areas throughout North America, Mr. Durham has aided every doctor to administer more successful hay fever therapy.
One result of these studies has been a compilation of definite information on the general dates of onset and termination of the several hay fever seasons in various lo-cations. In this connection, Abbott Laboratories supplies doctors, with graphs of the daily variations in ragweed pollen concentrations in their own localities. This is a courtesy extended to all physicians merely for the asking. Their files contain data for more than one hundred fifty locations in the United States, Canada, and Mexico.
Keeping pace with recent hay fever developments, Mr. Durham has extended his pollen studies to include fungi spores.
With the increasing importance placed upon discovery of cases sensitive to fungi spores, Mr. Durham has devoted greater attention to its prevalence. From 1933 to 1941 he has completed the staggering total of eighty investigations on fungus spore counts in as many localities.
The record of Mr. Durham's work stands as a monument to his efforts.
Dr. Robert A. Cooke and Associates
While Durham specialized in hay fever field work, Robert Anderson Cooke wrestled with hay fever in the clinic. Literally he has devoted a lifetime to the study and practice of hay fever and associated allergies. His researches span more than three decades of endeavor with the end not yet in sight. Dr. Cooke has not been a cloistered lab-oratory technician but rather a practical scientific clinician. Neverthess, he has spent more than his share of long weary hours in the laboratory with microscopes, test tubes, and chemicals, seeking for the solution to the action of hay fever pollens. Many and varied have been the investigations in hay fever conducted by Dr. Cooke and his colleagues. Largely through their efforts, we are gradually approaching the mastery of the hay fever mystery.
Very early in his career, Dr. Cooke exhibited his scientific bent. First Van Helmont, then Elliotson's lady, later Dr. Wyman, and subsequently many others, spoke of the family tendency of hay fever and other allergies. With little ado, Dr. Cooke in collaboration with Dr. Vander Veer collected and presented statistical evidence to prove the actual degree and nature of the role of heredity in hay fever. Following this in 1918, Dr. Cooke reported that house dust was a specific allergen, responsible for producing hay fever and asthmatic attacks in many persons. This discovery was momentous indeed. The true importance of dust as a major allergic irritant only came to be realized after Dr. Cooke's disclosure. From that time on, doctors have been guided in bringing amelioration to thousands of dust sensitive individuals whose trouble was previously unrecognized.
On the heels of Noon and Freeman's first papers Dr. Cooke published an article recommending an improved method of standardizing pollen extracts. He suggested standardizing these extracts by the amount of their nitrogen content. He worked out a table of dosage based on this method of standardization. It was early recognized to be superior to the method suggested by Noon. However, in 1933, with the aid of the chemical expertness of that probing biochemist Arthur Stull, there was introduced by Cooke and Stull a new method of standardizing pollen extracts. In this new method, pollen extracts are standardized on the basis of the amount of nitrogen in the protein or active substance of pollen extract.
The significance of these developments are not to be underestimated. Unfortunately they have not been universally understood or adopted by medical practitioners. Nevertheless when properly applied, these refinements are a means of greatly improving the results of pollen therapy, which is by no means perfect as yet. Toward this goal of perfection, Robert Cooke has worked incessantly.
In his strivings, we have been informed, by Dr. Cooke himself, that he rarely worked alone. His associates were often experts in a specialized branch of study. Invariably they were accomplished and talented experimentalists. Testimony of their excellence, and the acumen of their pilotage, is the fact that they have contributed more to the improvement of hay fever therapy than any other group in the world. Let us interrupt our story to introduce the men and background of what we may call the Cooke School of Hay Fever Research.
Early in his career Dr. Cooke was influential in establishing one of the first allergy clinics in the United States. At the New York Hospital Dr. Cooke served as director of the clinic. Working with him at the head of the lab-oratory was Dr. Arthur Coca. Since that time, Dr. Coca has remained active in hay fever research. He has employed his laboratory talents in the development of improved fluid extracts and solutions used in the diagnosis and treatment of hay fever. Many of the preparations used by present day physicians bear his name.
The New York Hospital Clinic and the Roosevelt Hospital Clinic in New York now represent to the field of hay fever what the Mayo Clinic is to general medicine.
To work with or under Dr. Robert Cooke seems to signify assurance of a successful destiny in the field of allergy. It is as good as the Midas touch. The first one to come under this charm was Dr. Albert Vander Veer who has been intimately associated with the work of Dr. Cooke for thirty years. Dr. Vander Veer is now assistant director of the Roosevelt Hospital Clinic.
Tracing the paths of some of Dr. Cooke's former assistants and associates this is what we find. Dr. Mathew Walzer, an early worker at the New York Hospital, is now head of the allergy clinic at the Brooklyn Jewish Hospital. Dr. William Spain, another early associate, now directs the Post Graduate Hospital allergy clinic in New York. Dr. Aaron Brown is head of the Bellevue allergy clinic in New York. Dr. Robert Chobot is in charge of the pediatric allergy clinic at the Post Graduate Hospital. Dr. Samuel Bell directs the pediatric allergy clinic at the Bellevue Hospital. More recently, Cooke assistants who have gained a place of recognition in the field of allergy are Dr. Stanley Hampton of St. Louis, Missouri, and Dr. Selian Hebald of New York. Dr. Hampton's brilliance was recently made known to the medical world by his undisputable demonstration of the allergic basis in a case of Henoch's Purpura. This disease has been recorded in medical textbooks as suspected of having an allergic origin. It is characterized by escape of blood from the vessels into and beneath the skin and mucous membranes. The United States Army is now the benefactor of Dr. Stanley Hampton's services.
The most recent work at the Roosevelt Hospital has progressed through the inestimable skill of Dr. William B. Sherman and Arthur Stull, Ph.D. The sterling research efforts of these two men has been interrupted by their entrance into the armed forces of the United States. Their very last and most ingenious achievement in collaboration with Drs. Hampton and Hebald consisted of chemically splitting apart the viperous pollen extract. Thus far they have succeeded in distinguishing three chemically different parts. Each part is called a fraction, the three parts have been labeled fraction one, two and three. The first, resembles vegetable albumin, the second, vegetable proteoses and the third, plant glutelins.
Each of these fractions has been found to have irritating or antigenic properties as it is called. But the important fact is that they are found to exist in different proportions in any sample of ragweed pollen extract, and moreover they differ in their degree of irritating action on different hay fever patients.
Other experimenters have attacked the problem of fractionating pollen extracts by an entirely different method. Dr. H. A. Abramson and his associates, working at the laboratories of the Mt. Sinai hospital in New York have reported splitting ragweed and timothy pollen extract by what is termed electrophoresis. But as yet they report no information on its application.
Thus it becomes evident that the original explorations started by Dr. F. W. Heyl in 1917 are by no means at an end. Dr. Heyl conducted one of the earliest and most extensive researches in an attempt to find the chemical secret of hay fever pollens. He described them well but could say little about their whys and wherefores. Our modern researchers are telling us a little about the actions of pollen extracts but have not advanced very far in their knowledge of the chemical secret.
Although this work on pollen extract fractions is admittedly in its experimental stage at the Roosevelt Clinic, some success in applying its principles has been observed. Difficult cases at first treated unsuccessfully with the whole extract of ragweed pollen, are tried out with treatment by pollen extract fractions. Thus far, some patients have been found to obtain greater protection and sustain needed higher dosages without constitutional reactions, when treated separately with the fractions of the extracts to which they are sensitive. Controlled experimental results on this type of treatment will not be forthcoming for a long time.
The last Cooke disciple to gain notoriety is a lady. Dr. Mary Loveless started out under Dr. Cooke's wing in 1935 but has branched out on her own with recent research that portends to have far-reaching effects. Her story is an interesting one, and is tied up with the very last word in hay fever research.
In the notable paper of 1916 on human sensitization by Drs. Cooke and Vander Veer we find these words: "Experiments to determine the exact nature of the protection in hay fever are now being undertaken." In 1935 in the summary of an article by Drs. Cooke, Barnard, Hebald and Stull we find the following: "We have made studies to determine if possible the mechanism of the protection afforded by specific injections."
It is obvious that the problem of determining the nature of the protective mechanism obtained from hay fever treatment was not an easy one. Nineteen years of chasing chemical rainbows is a long time. However, the conclusions of the 1935 report were somewhat encouraging. The authors indicated that a blocking or inhibiting type of immune antibody seems to be developed as a result of hay fever inoculative treatments. Two years later following up on this first glimmer of light, Drs. Cooke, Loveless and Stull reported another advance. They showed evidence that this immune or so-called blocking antibody, appears in the blood of non-allergic persons as a result of injections with ragweed pollen extracts.
The latest episodes in this story are written by Dr. Mary Loveless alone. In 1938 she transferred her affections from the Roosevelt hospital clinic to the New York hospital, where she now presides over a laboratory of test tubes and intricate chemical paraphernalia. With this apparatus at her disposal and her feeling that somehow there must be a way to trap the immune antibody she went to work.
The presence of a sensitizing antibody in the blood of allergic persons had long been known. This you may re-member was clearly demonstrated by the P-K reaction and by transmission of sensitivities through blood transfusions.
Now it appeared that another antibody, an immune antibody, was developed in the blood of treated hay fever patients. It became Mary Loveless' task to prove it. This she did by a well planned experiment. Dr. Loveless knew that the sensitizing antibody could not withstand heat. She had previously learned that the immune antibody could withstand heat. She took some blood serum from treated hay fever patients and untreated hay fever patients. The serum of the treated hay fever patients was heated. Now if an immune antibody was present in this serum, the heat would destroy the sensitizing antibody and leave the immune antibody alone. And so it was. This she proved by showing that the heated serum from the treated patients was able to neutralize the irritating effects of rag-weed extract on ragweed sensitive patients. The heated serum from untreated patients contained no such neutralizing power. Thus proving that an immune or blocking antibody is developed in the serum of hay fever patients who are treated by injections of ragweed pollen extract.
What is the significance of Dr. Loveless' accomplishment? Just this. By means of this discovery she has gone on to show that the amount of immune antibody developed in a patient is proportional to the amount of hay fever relief he can obtain from inoculations with ragweed pollen extract. Thus we are on the road to one hundred percent hay fever protection. There remains only the need for a method of developing in the hay fever sufferer large enough doses of immune antibody. Although work along these lines has been undertaken, it has not yet been satisfactorily established. However, Dr. Loveless hopes to be able to do so shortly.