KARL LANDSTEINER

BY ELLIS FULLER
APRIL 10,1973
INNOMINATE SOCIETY

He specifically devoted about 90% his adult waking hours, over 50 years in scientific pursuits. His specific interest was in unraveling the mysteries of the nature of the antigen antibody reaction.

His book, which remains a classic today, The Specifistics of Seriologic Reaction is still in print.  In fact, so much was the term "specific” or “specifistic" associated with Dr. Landsteiner that a friend once wrote to him requesting a photograph that would define “your own specifistic.”  Dr. Landsteiner, in the letter that accompanied the picture he sent back, said that the "pictures should define a specifistic, at least if tested against the lower primates. I’ve been familiar with some of Dr. Landsteiner's contributions in the field of transfusions because of my association with blood banking over the last ten years.  But it wasn't until I really began to dig into his life and work in preparation for this paper that I came to an appreciation of the really amazing amount of work that this man did, which was of very fundamental and basic nature that has very great application to many fields of medicine today.  It has been said that a great mind tends to grapple the basic issues, whereas a small mind instinctively contents itself with minor problems.  I think in reviewing the interests that Dr. Landsteiner had in the work that he did one has to be impressed with the very fundamental and basic nature of this work.  He was a prodigious worker.  He produced some 346 papers over his life span, and he worked up until his death at the age of 75.  At the time of his death the Journal of Immunology published his complete bibliography, and I think it is of interest that a quotation from William James was appended to this bibliography, “The great use of life is to spend it for something that will outlast it." He is best known for his description of the A,B,O Blood group system, work he did in 1900, and for which he received the Nobel Prize in 1930. But by his own statement, he did not feel that this really was deserving for such great acclaim.  He thought that some areas of interest were perhaps more important work.  He, in fact, did this work and appended the information for which he received the Nobel Prize as a footnote to another article, and even in later years when he collected his selected group of his scientific writings, and had them bound as a memo for his family as a keepsake, he didn't even include his Nobel Address in that group.  It has been said by many of his friends who have written about him that he was truly a humble man, and this would appear to be true.  It is stated that a friend dropped by his apartment the evening after the award was announced with the plan of congratulating Dr. Landsteiner and his family on this great honor, and he found the Landsteiners sitting in the living room of the apartment reading oblivious to the radio or telephone, seemingly unaware that anything unusual had happened, as indeed Dr. Landsteiner's son, his wife were, because Dr. Landsteiner had failed even to mention the award to them.  But this observation that lead to the defining of a blood group system, which he tended to make something light of, as are many observations that are rather simple, by a prepared mind who recognized the importance, has been one of the major advances in the field of medicine, perhaps leading to the saving of as many lives, I suppose, as almost any observation we know of.  As a brief background to outline the import of this contribution, I might just hit some of the highlights of the history of the art prior to that time, and it was an art, rather than a science. There had been interest in using blood as a therapeutic agent since antiquity.  There are numerous reports of blood given from animals or young warriors with the hope of imparting their characteristics, of gentleness, kindness, bravery, or frequently, virility, to the recipient depending on their needs usually by drinking. It wasn't until Harvard's description of circulation in 1628 that a progressive group of young scholars that formed the nucleus of the famed Royal Society, which I'm sure many of you are aware of, including among membership such notables as Robert Boyle and Christopher Rand, became interested in giving medication by the intravenous route.  In fact Sir Christopher Rand organized a series of experiments in which they administered drugs and alcohol to dogs and made them quite drunk.  Before this society in 1665, Richard Lower gave the first demonstration of a direct transfusion of blood from one dog to another, successfully.  And additional transfusions with animals were performed, and it was planned to transfuse humans.  But scientific competition apparently was so in those days as it is today, and a physician in France got the jump on a group of the Royal Society, and Dr. Jean Baptiste Denis who was physician to Louis XIV, and in fact a member of the Academy of Science which was formed by Louis in direct competition to the Royal Society.  And he knew of Lower's work, and he gets the credit or perhaps the blame for giving the first transfusion in man.  It is recorded that in 1667 he was brought a youth who suffered from fevers and who was exhausted because of numerous phlebotomies, and he elected to treat him by transfusions, and after performing a phlebotomy of about 10 ounces, he administered 8 or 9 ounces of blood from a sheep, apparently without adverse effect.  The second transfusion was given to a healthy volunteer, and the third one into the son of the Prime Minister of Sweden, who was moribund at the time and died shortly thereafter, but none of these people had apparent ill effects from the transfusion.  He was then late in 1667, bought a manservant, 34 years old, Antoine Mauroy, who was recently married, who was given to fits of insanity in which it was recorded that he became a raving maniac.

Dr. Denis elected to treat him also by transfusion, and administered some 9 ounces of calves’ blood, with the hope of imparting gentleness, and it's recorded that they had to interrupt the transfusion because of his violent behavior. But the next day, he was improved and he gave a second transfusion, this time in a larger amount, and there's a very classic description, Phelphile Bonet's, of this classical transfusion reaction which is too long to read, but he describes warmth along the arm and the arm pits, and sweat and irregular pulse, constriction of the chest, vomiting, diarrhea, and the passage of urine that was very dark containing hemoglobin from the broken down blood, which went on for several days.  But in spite of the severe reaction, he survived and in fact was reported to have marked improvement for the next two months, and then relapsed. So in December 1667, Mauroy's wife brought him back to Dr. Denis, insisting on another transfusion, and this was given with some difficulty because of poor cooperation and the next day, Mauroy died. Denis was charged by Mauroy's wife with murder, and a long legal battle ensued, from which Denis was ultimately exonerated, but the news of this type of treatment had spread widely over France and the physicians had become very concerned… this would correspond I suppose to the Heart Transplant in our time as far as dramatic therapy… been concerned that this new form of therapy might really replace all of the remedies to which they were aware. So they had sought to put an end to this, and so pressure from the physicians and concern about others and the population, the cause of the morale and religious aspects of this treatment, lead the Parliament of France in 68 to outlaw further transfusion therapy.  The law making bodies of a number of countries followed suit and this pretty affectivity halted transfusion for the next 150 years.  However there are sporadic reports of transfusion, including transfusion to humans by James Mondale in 1818 apparently with success, but some transfusions of humans were helpful and others were followed by similar severe transfusion reactions.  Now prior to Dr. Landsteiner's work in 1900, it was known that blood from animals could be different than blood from humans by seriologic methods and this had lead to the discontinuation of any further tips of transfusions by animal-blood.  Dr. Landsteiner in fact did take the next logical step, in seeing if there were seriological differences between the blood of various healthy human beings, and to do this he collected blood from members from his laboratory and used his own blood, separated the serum from the red blood cells and mized them back, in all possible combinations. And he found that in some of these mixtures, that blood and serum would mix with a smooth mixture with no reaction, others clumping in a group mixture, would occur.  Even if his observations were simple, his deductions were right impressive, and he then postulated that you could explain the phenomenon that he observed if you would postulate the presence of two substances on the surface of red blood cells, which he termed A & B substances or glutinogens and in the serum two antibodies or glutinins, anti A and anti B.  And from this work he knew that there would be four groups, depending upon whether one or the other or both or neither of these substances were present on the cell and the agglutinating substance and the serum would be present only if the corresponding agglutinogen were absent from the blood cell, and further observation confirmed this and the A,B,0 blood route system has remained essentially the same since that time.  But he immediately recognized that this had implications for transfusion therapy, for selection of donors, and also immediately became interested in applying blood groups to forensic medicine, identification of the source of blood stains or other body secretions, saliva seen in silac and did a great deal of writing on forensic medicine including The Use of Blood Groups and Exclusion of Fraternity.  His next major work in blood transfusion came after he left Vienna and came to this country, working with Dr. Phillip Levine, in which they were looking for additional blood groups.  They were only aware of this one.  And, to do this, they injected blood from humans into guinea pigs and rabbits and tested the serum from those injected back with human cells, and by this way, discovered the NMP blood groups system.  This hasn't proved to be very important as far as transfusion is concerned, but it has greatly enhanced the ability to identify blood, blood stains, and forensic medicine, exludes the term.  He became convinced that blood was very complex and the blood group system would be as individual as the fingerprints, and this has certainly proved to be true.  His last major contribution in blood banking came when he was past 70 years old, working at the Rockefeller Institute with Dr. A.S. Weiner.  Dr. Weiner is one of the famed men in blood transfusion, a rather obnoxious fellow by all reports. 

But I did write to him to see if I could get some additional information about Dr. Landsteiner and got back a sweet letter.  I guess Dr. Weiner is in his 80's now and he not only sent me some articles, but offered to review the manuscript and said if you're in N.Y. he’d like to have me out to dinner, because he thought so much of Dr. Landsteiner.  The work that they did, they were attempting to find if there was similar blood groups in humans in some of the higher primates.  And so to do this they took red cells from the Rhesis monkey, injected it into guinea pigs and rabbits again, and then tested the antibodies formed against the anti rhesus cell, antibodies against human red cells and found that in act about 85% of the Caucasian population did react positive by about 15% negative, and named this group the RH blood group system, and immediately recognized that this group system accounted for many of the previous and unexplained transfusion reactions and multi-transfuse patients who otherwise ABO compatible.  Shortly there after using this work Dr.

Phillip Levine who had previously worked in Dr. Landsteiner's laboratory found that the RH system was a system involved in most of the cases of erythroblastosis foetalis in using hemologic principles. Many of them worked out by Dr Landsteiner; the exchange transfusions were developed and saved hundreds of babies.  More recently the anti RH antiglobin of the _____________ that has done a great deal to preventing this problem. So Dr. Landsteiner's contribution to the field of transfusion is considerable and he does well deserve the title as father of this program.  Dr. Landsteiner was a private man and it was difficult to find a great deal about his personal life and characteristics.  He was born in Vienna, January 14,1868, of Jewish parents, his father Leopold was a journalist and died when young Karl was only 6 years old.  It's reported that Leopold's journalistic style was a very austere type and this was certainly very much a characteristic of Dr. Landsteiner's writing.  His mother was a very dominant person, in Dr. Landsteiner's life, but herself was a very retiring person, in fact companions who knew Karl, when he was a boy, in later life couldn't even recall having seen Mrs. Landsteiner. Yet so domineering was she apparently, that Dr. Landsteiner did not announce his marriage, which occurred rather late in life, about 47, till after his mother's death. Dr. Peyton Rausch notes that her death mask hung on his bedroom wall, throughout his lifetime. He and his mother joined the Catholic Church, when he was a boy. I could find nothing about his religious activities. He did declare himself to be a Catholic in a public statement, some 50 years later.  He attended the gymnasium in Vienna in 1885, entered the Medical School at the University in Vienna, graduating in 1891. At that time he published his first paper, “The Influence The Diet on The Blood Ash Composition”, indicating an early interest in research and a particular interest in basic chemical research.  In fact, immediately on graduation he left medicine entirely for the next five years, and studied chemistry under recognized leaders in the field of that time.  Hantzsch in Zurich, Amil Fischur in Wurzburg, and Bamberger of Munich.  And at the end of five years he returned to Vienna under the professorship of Max VonGruber, and in 1898 went back to the University of Vienna under Professor Weichselbaum, who discovered the bacterial cause of meningitis and was co-discoverer of the pneumonococcus.  During this time, he did much of his early work including the description of the A,B,0 blood group system, and his interest really varied, he began his interest here on immunology.  I’ll talk about this in a little more detail in a minute; we just might briefly hit on some of his other contributions, which would have made him outstanding in itself. Dr. Landsteiner made three major contributions in this field; he was able to successfully transmit the infection from man to ape. He developed the technique of identifying the spirochete by the dark film microscope method; again a discovery that he tended to downgrade in importance, but it has remained until the present time, the definitive method of positive identification of the spirochetes in active lesions. He also took similar pride in the improvement in the _____________ reaction when he showed that antigen from beef pork, normal beef pork muscle could be substituted for the previously used infected tissues of the thesis spirochetes not only a safer and easier test, but a more sensitive test. With Donver in the laboratory they unveiled the mysteries of the previously completely unexplained paroxysmal hemoglobinuria. This conditions where half exposure to colds, individuals would pass hemoglobin in the urine, and become anemic and this was completely not understood. Dr. Landsteiner and Donner showed that this was due to a cold active antibody that would react with red cells, when the individual was exposed to cold, and then caused ________________ when the red cells returned to the wrong circulation.

There was great concern at that time about the spread of syphilis, as there is great concern in our time about the spread of syphilis. And the in vetro illustration of this phenomenon where you incubate blood in the cold and allow it to warm and measure the _________ remains the definitive diagnostic test for this condition at the present time.  Plus one of his major contributions, outside of his major field was in infantile paralysis, a recent dread disease at that time, and he first showed that you could transmit the disease by hrinding up the central nervous system material from someone he did an autopsy's on, and injecting this material, a cell free...infiltrated this material into monkeys and caused a typical disease and postulated the disease must be caused by a virus and in subsequent years with co-workers he did indeed demonstrate that it was secondary to a virus and one of the smallest that we know. All this work being done at a time when he had a very heavy load of pathology I talked to Laslo Mark about Vienna at that time and he said that pathologists were expected to do up to 2,000 autopsies a year, and a very heavy teaching load.  In 1916 he married Helen Wlasto, they say he was 47 years old at the time.  We know nothing about her except she's described as filled with sweetness, gayety, and devotion, and I told my wife, I presume, that those were desirable qualities for a wife to have. They had one son Ernest, who ultimately graduated from Harvard Medical School, and who practiced Urologic Surgery in Boston and now lives in Providence, Rhode Island, at least I guess he does.  I also wrote to him, hoping to get some information and didn't get an answer. I don't know if psychiatrists are here to explain this, but didn't hear from Dr. Landsteiner. But by this time the conditions in Vienna were becoming very difficult for any scientific pursuit because of the problems associated with the First World War, and it's stated that Dr. Landsteiner could not even work in his laboratory because of his cold. No method of heating. He was of restless nature and when the poor of Vienna finally cut down the trees around his house and tore down his fences to use for fire wood, he determined to leave Vienna for he saw no future for Austria at that time.  And this in spite of the fact that he by this time had considerable world renown had a guarantee of personal freedom and a guarantee of patients for the rest of his life if he stayed there. But with the help of Professor Von Leeuwen of Leyden he obtained a position as prosector at the R.K. Ziekenhuis at the Hague. This was a small Catholic hospital. Again he had heavy routine duties, at a very small salary, and by this time received so many visitors on a constant… two or three, had a hard time getting much done. He was there for a little over three years, producing some twelve papers about five of which Were in Dutch which he learned very quickly. But the situation was very difficult, and friends in this country at that time, knew of his conditions, and through the aid of Dr. Simon Flexner, attained for him an invitation to come to the Rockefeller Institute, which he did in 1943, now being 55 years of age. It's reported that when he arrived in New York someone asked him what kind of place held like to live and he said well he’d like to have a small cottage by the sea, with a rose garden, similar to that he had had in the Netherlands for about $50 a month. Well he ended up in a second story flat over a butcher shop on a trolley car line at three times the price, but he always expressed great satisfaction with his move to this country, and became an American citizen as soon as he was able, and it's reported that he learned English with great zest, and if you look through the bibliography you'll notice that most of the papers in the later part of his time were in English. The last 20 years of his life, from 55 to 75 were again amazingly productive.  For the first time he had adequate laboratory facilities, he had freedom from marked routine duties and was recognized as an outstanding leader in this field. He produced 160 papers, and remarkable even grouping over the last 20 years of his life, in fact, it's mentioned the RH group, one of his major contributions was done, when he was in the 72,73 year age range.  He continued to work in his laboratory up until two days before his death, at the age of 75 and died on June the 26th, 1943.  And it was reported in his obituary, by Dr. Stano Jones, that his mind was as young and fertile at that time as when he began his scientific career.

I’d like to just interrupt a minute to show you just a very few slides. This one is from a print showing Christopher Rand and Robert Boyle in the lower right in the transfusion experiment before the Royal Society. This is an old print showing one of the early transfusion experiments where you ____________ blood in one arm and take it out of the other. This was a picture taken from an advertisement. It shows a good nation in the testing for the RH blood route system, much as is done in the blood banks today, and this essentially was an experiment that Dr Landsteiner himself did which really hasn't changed very much since that time, of which he identified A cells with anti A serum and on through.  The next group of slides ________________Coloned ______________ Camp of Fort Knox. Fort Knox as some of you know is the major army blood transfusion research center here and               and very much interested in blood transfusion history and particularly Dr. Landsteiner, and so I had invited him to come.  I thought that his discussion would be much better than my paper, but he's in Washington, but he sent some wonderful slides of Dr. Landsteiner. I’m very grateful for that.  Let’s run through them very quickly.

Dr. Landsteiner received many awards. This is The Dutch Medal. He received an award from France, the Nobel Prize Award, as I already mentioned. And then a group of pictures which show him...he was a very militaristic-looking person. And this was the Paul Herlick Award. He was president of many organizations and received so many awards. He did receive a number of honorary degrees. I was king of impressed with three from pretty good country schools. He got Dr. of Sciences from Harvard and Cambridge, and the University of Chicago. A final word about the work that Dr. Landsteiner really was most interested in, and himself considered his most important, that was in the field of Immunology and I suppose immunology would have to be considered the hottest field in Medicine today. And his contributions are certainly very pertinent in this regard. In fact workers in the field of immunology have stated that they felt that perhaps Dr. Landsteiner was even more deserving for his work in this field than for the A,B,0 blood grouping system for which he did receive the Award. In 1970 the New York Academy of Sciences had the Landsteiner Memorial Memory Conference and Dr. A.J. Kuhns in the introductory remarks to that conference, noted that it was not customary for the academy to have conferences of a commemorative nature, but that it did seem particularly appropriate at that particular time because of the debt owed that modern Immunology owed to Landsteiner's thought and work. He did many things. Perhaps his main contribution was in demonstrating the Specifies of the Antibody. It was known that if you injected a foreign protein into an animal, that an antibody would be formed under the right conditions, that this would be a very specific antibody so much so that you could differentiate the same protein in different species. Because actually there's nothing known about the nature of this reaction, till Dr. Landsteiner's work.  And he clarified this by development the technique of applying a simple compound of known chemical structure, that would not in itself be antigenic (because it took a full protein to do this) but if you would attach this structure of which he knew the composition to a carrier protein and the protein plus the attached group which he termed a haptine, would become antigenic in fact the antibody was formed against this protein haptine complex, the specificity of this antibody would be largely determined by the composition o£ the Haptine itself.  And this has been described as the greatest single step forward in the history of immunology, because it at once transformed the science from the state in which nothing was known about… what about a protein causing an antibody to be formed… some mysterious undefined property to the point where the very nature of the antibody could be studied based on the known chemical composition of the antigen causing antibody formation. Working further with this, it looked initially not only had the haptine, or the known chemical compound needed to be attached to the protein, and you saw this reaction because of the precipitate, and if you added haptine to the antibody, no precipitation was observed but again Dr. Landsteiner reasoned this was not likely to be true, because the majority of the antibody combining site was determined by the haptine and reasoned that some reaction probably did take place even if it wasn't observed in the test tube.  And he demonstrated this by technique in inhibition where he took the haptine, mixed it with the antibody first, and then mized the whole antigen, the protein antibody, and showed that the expected reaction did not take place. In other words, the haptine of the substance of known chemical composition had a both ________ and dexro forms, in other words, it would differentiate just on the special relationship of the material around this carbon atom. And the demonstration of the haptine itself would react, in which you could demonstrate this by the inhibition reaction, has been very helpful in allowing us to study many compounds without first attaching them to proteins, and this has led to the development of many endocrinological tests, the inhibition reaction, the _________________ fixation test, and more recently, the very important radio amino acid techniques which, by using the correct specificity of antibody formation against simple substances and also attaching a radioactive tag to the antibody, you can measure minute quantities of almost anything in the serum such as drugs like kigitoxin, or vitamin B12, hormones, like growth hormones, virus particles like hepatitis- associated antigen and I think we just begin to see the application of this technique which allows us to measure many things previously unmeasureable at a rapid time, whereas before it would take a rather crude essay over a great length of time, at a great expense.  Without going into any great details, the principles outlined by Dr. Landsteiner had been ____________ I would like to just mention his book The Specificity of Serological Reactions and I say this remains a classic.  At his request, Dr. Linus Pauling wrote the last chapter of this book, The Molecular Structure and Intermolecular Binding, and these two out-standing scientists both Nobel Prize award winners...who had different but complimentary interests, thought that they had a great deal to learn from each other, and it's reported that Dr. Pauling gave a series of lectures at Cornell on the nature of the chemical bind and Dr. Landsteiner unexpectedly appeared in the audience. And in the ensuing 4 days of the conference, they spent a great deal of time in conversation.  Dr. Pauling has been reported that in those 4 days he received the world's greatest course in immunology by Dr. Landsteiner.  But the work that Dr. Landsteiner has done not only makes him founder of transfusion but also deserving the title of Father of Immunology.  And it's applications go directly to such things as understanding the mechanism of allergy, resistance to infection, a very great recent interest of course, hypersensitive diseases, the immune complex diseases, the fundamental problems of tissue transplantation, relate to the immune mechanism...solving these problems.  Perhaps the most recent major development in this fields has been recognition in accordance of the immune surveillance mechanisms of the body as far as inhibition cancer formation, and also the recent very encouraging work with hemeno~therapy as far as treatment of certain malignancies such as ______________and certain cases of acute leukemia.  I think one indication of the ______________ of this and the publics interest in this was the recent issue of Time of March 19, with Robert Good, the current leading immunologist perhaps in the world, as the cover picture and the cover story, I'm sure many of you have read this.  I"11 also pass around the two of a series of seven translations that the army has done, under Colonel Camp's direction, translated many of Landsteiner's earlier papers from German into English and other papers _________________ history of transfusion.  He says incidentally that this group of 7 would be available to any member who would like to have it, if they would request this.  I’m sure if you don’t have it in the library, you's like to have...Finally, I'd like to just read to you some direct quotations from some of the obituaries about Dr. Landsteiner by some of his friends, Dr. Weiner, Dr. Levine, Dr. Stanhill Jones, Dr. Merril Case, and particular Dr. Pate Rous.  Now I've just kind of selected these and tried to organize them to try to give you a little insight into some of his personal characteristics, some of his strengths and weaknesses.

“So severely objective was he that when he began to make discoveries he reported what he had found fact by fact, as soon as he was sure of each, with no thought and time given to fu1l dress presentations this became a life long habit.”

“So inured was Landsteiner to routine that he figured that he might not handle himself wee in a life free from it.  In the laboratory he was full of confident energy and enterprise.  He did not deviated from his routine. Social activities he avoided; in his view the day was for experiment only, reading and thinking could be done at night - until a late hour.   He covered wide reaches of the medical literature, scanned abstracts of articles for mental relaxation and was ever the first at current journals, feeling crestfallen if someone mentioned a paper that he had not seen.  To open mail and break wrappings on scientific journals gave him eager pleasure.  His energy was continuous and compelling and no moment of idleness in the laboratory was tolerable to him.  To himself new ideas came endlessly and he was continually suggesting trial experiments "which would take no time.”         He went to great length to assure him that what he thought he observed in the laboratory actually had happened.  Of this he was incorrigibly doubtful and when a discovery declared itself he would instantly conclude that it could not be real and would set about to make this plain.  In thus striving to pull down, he not only buttressed but often built further.  Pertinent experiments were done many times over and not until the data on a point under determination were in his term, “thick" would he publish.  Beyond making his papers true Landsteiner made no effort to make them easy saying that what was in them could be had by anyone that really wanted it.” 

Though accessible to visitors, they wore on him. When he spoke in public it was with an air of misery and nothing but solitude would do for him on a holiday.”

"Landsteiner had a mind that was by nature sharp edged and rigorous delighting in the exact. He read higher mathematics for diversion, amused himself with problems of advanced algebra and calculus and followed with zest each forward step in the new mathematical physics.

The inexact was so hard for him to endure that he left unpublished most of the results of some six years of his work on serological responses to protein digests because of not being wholly sure of all that latter contained."

“During Landsteiner's last year the forlorn state of civilized man weighed heavily on him: No new victory of the allies sufficed to dispel the dread that Nazi would triumph. He had a sense that the new ways of living were very wrong - for though constantly searching for the new in science he held to the old fashions in those things that touched him personally.  He found life increasingly harried; only in science could he find tranquility and security. He was preemptory by nature but he was downcast too, self-questioning and never sure in his human relations. Not only toward his scientific findings but toward all else he was a pessimist saying that life had given him no reason to be other-this despite his renown, the applause and rewards of the world.  His pessimism was sad, not bitter and never obtrusive, despite it he had cheered others in what they were trying to do. But he was held in the grip of his temperament and gradually this tightened upon him: Only in his scientific life was he secure, serene and whole.” "Liking came to him, for he was simple, sincere, modest and gentle and witty as well in a shy way. His warring attributes showed only in his face.”

“In the obituary by Dr. Pate Rous, he summoned it up eloquently in saying “Few men who work at he problem of human disease come to the mental stature of which they are capable. So much there is to see and to do by the way, such opportunity to gain large practical ends by small mental means, so much pulling and hauling by the lay public and such wide applause for second, third, and fourth achievement, if only it be of use, that to fall away from the line of intellect is all too easy.  A few men there are, though, who cleave to it through thick thin. Karl Landsteiner was one of these."