Alan G Baxter

Comparative Genomics Centre,
Molecular Sciences Bldg 21, James Cook University,
Townsville, 4811, Queensland, Australia
Telephone: 61-7-4781 6265 Fax:  61-7-4781 6078

Broadcast 25/6/2000

Robyn Williams:
          This year we celebrate the centenary of a discovery without which you could well be dead. Or never have been born. There's a good chance too, that someone near and dear at least wouldn't be alive. I'm talking about the discovery of blood groups, and from them, the elucidation of immunology in general.

          The story is told by Dr Alan Baxter, Head of the Auto Immunity Group at the Centenary Institute in Sydney. His book, just published, is called 'Germ Warfare' and then, in case you’re misled and think of Saddam Hussein, it's called 'Breakthroughs in Immunology.' It has a delightful Foreword by our latest Nobel Laureate, Peter Doherty.

          Well here's Alan Baxter.

Alan Baxter:
          I have, before me, the record At the Drop of Another Hat, which was produced by George Martin, of Beatles fame. It is the second of three albums of songs and anecdotes by Michael Flanders and Donald Swann. Swann wrote the music and Flanders wrote the words. Their greatest hit was The Hippopotamus Song - an ode to mud, mud, glorious mud.

          On the record sleeve is a photograph of the pair of them at the Fortune Theatre in London. Swann, seated at the piano, is slight and bespectacled - reminiscent of a parish church organist. Flanders, a huge bear of a man, is hirsute and six foot three, and is seated in a wheelchair behind Swann. Usually they sang together. Occasionally, Swann would sing alone, accompanying himself while Flanders horsed around in his chair - raising laughs with his covert antics. Between the songs, Flanders would provide links, textual detritus, by way of introducing the next composition. His link for their song on the first and second laws of thermodynamics went something like this:

          'One of the great problems of the world today is undoubtedly this problem of not being able to talk to scientists, because we don't understand science. They can't talk to us because they don't understand anything else, poor dears. This problem, I think it was C.P. Snow who first raised it in his book Science and Government  - he says, it's no good going up to a scientist and saying to him as you would to anybody else, you know, "Good morning, how are you, lend me a quid" and so on. I mean, he'd just glare at you. Or make a rude retort, or something. You have to speak to him in language that he'll understand. I mean you go up to him and you say something like, "Ahhh, H2SO4, Professor! Don't synthesise anything I wouldn't synthesise! Oh, and the reciprocal of pi to your good wife." This, he will understand.'

          This problem of communication between scientists and the public is rather worse in my own field, Immunology, than most. It was therefore something of a surprise for me recently to find an article on immunology in one of the newer women’s magazines. "Most of us never think about our blood group." it started, "Unless you have actually been wheeled into ER on a trolley, drips held high, you may not even know what yours is. However, if you were to trawl through the medical literature, you'd find there are well-recognised links between certain diseases and blood groups."

          "Wonderful!" I thought. In addition to the normal blood groups that everyone is familiar with - the ABO blood groups of red blood cells that determine transfusion compatibility - there is a system of white blood cell groups that determine organ transplant compatibility. While the ABO blood groups have very slight associations with the intestinal problems of gastritis, duodenal ulcer and stomach cancer, it is the latter system which contributes in a major way to the risk of developing many other diseases such as childhood diabetes, lupus, and certain kinds of arthritis. I was surprised and delighted that a popular magazine would take on the task of explaining such an association.

          I read on. "The key to what we eat... lies with our blood group. So 'O's need a certain amount of meat, 'A's do best as vegetarians, 'B's are good with both meat and vegetables and can handle dairy products as well, and so on." Now I was confused. I looked around the page for some sort of explanation, and found there was a text box headed Blood Power next to a colourised scanning electron microscope picture of a clump of red blood cells. The text read, "When blood cells encounter food that they identify as an 'enemy', they clump together and this can upset the body's system. Different blood types identify different food as foes - type 'B', for example is fine with milk, while 'A's don't like it."

          Now this is nonsense. Red blood cells don't recognise foreign targets. White blood cells do. And clumping? Specialised protein molecules in the blood called antibodies can clump bacteria, but the clumping of red cells in the blood is not a mere "upset" to the body’s system, it is a disaster that can result in strokes and heart attacks... But let's start at the beginning.

          In the case of the ABO blood group system, the beginning was Karl Landsteiner. Landsteiner was born in Vienna in 1868, trained in medicine at the University of Vienna and became a research assistant at the pathology institute there. He was a tireless worker, rigorously exacting and unerringly accurate in his observations. At the turn of the 19th Century, he published the work for which he later received the Nobel Prize: his description of the ABO blood groups.

          At the time, it was already known that blood transfusions are fraught with danger. Transfusions from animals to humans were almost always associated with clumping and dissolution of the red blood cells within the veins of the recipient. The resulting release of haemoglobin frequently caused severe kidney damage and subsequent death. Transfusions of human blood were occasionally tolerated; more frequently if donated by relatives of the recipient than if not.

          Landsteiner's approach to this problem was to separate blood samples from several volunteers into the red cells, which he washed in a saline solution, and the fluid in which they circulate in the body, the serum. He mixed red cells and serum from different pairs of people together on microscope slides and carefully tabulated the results. For example, his own serum was able to clump the red cells from four of his laboratory colleagues but not those from his own blood or that of another doctor. By comparing the reactions between serum and cells from each pair of individuals, he was able to divide his experimental subjects into three groups: 'A', 'B' and 'C'. He wrote that in the case of 'group A' patients, "the sera reacted with cells of another group ('group B') but not the cells of 'group A', while the 'A' cells were affected by the 'B' serum in the same manner. In the third group ('C'), the serum agglutinated the cells of 'A' and 'B', while the cells were not influenced by the sera from either 'A' or 'B'."

          He later revised his classification slightly. There are now four red blood cell types: 'A', 'B', 'AB' and 'O'. Type 'O' cells never clumped and it was subsequently shown could be safely transfused into anyone. People with 'O' type blood are universal donors. Type 'AB' cells were clumped by every other type of serum. They had on their surfaces something to which the agglutinating factors of foreign serum could bind. Type 'A' cells were clumped by both type 'B' and type 'O' serum, but not 'A' or 'AB'. Similarly, type 'B' cells were clumped by type 'O' or 'A' serum but not by type 'B' or 'AB'.

          Landsteiner’s careful tabulation of results from family members revealed that the blood groups were inherited. As with almost all genes, there are two copies of the blood group gene - one inherited from the mother and one from the father. Landsteiner realised that each of the two copies could be one of three variants - A, B or O. An individual who inherited A from both mother and father ended up blood type 'A'. One who inherited A from one parent and B from the other was 'AB'. The 'O' blood type resulted from the failure to inherit either the A or B variants of this gene. This pattern of inheritance explained why transfusions from family members were more likely to be successful than those from unrelated strangers - there was a greater probability that they had inherited a compatible blood type.

          We now know that the clumping factor in serum is antibody. Antibodies are specialised target-specific molecules which are produced in response to infecting organisms, and which act to direct the immune system against them. The surprise with the ABO specific antibodies is that they are present before the body has ever been exposed to the targets. We now know that these particular antibodies are rather weakly binding and are only poorly specific. They act as a sort of 'first resort' early in infection, since they bind to almost anything. Of course the only thing they must not bind to is the body's own tissues, or else they would cause all sorts of havoc. And so they don't. The antibodies in the serum of a person with 'A' type blood don't bind 'A' type blood cells, while type 'O' people, who don't have either the 'A' or 'B' targets on their red cells, have antibodies against both blood types circulating without causing any problems.

          Landsteiner's 'bloody minded' devotion therefore provided the information, and the clinical tests, required to render blood transfusion feasible. But his contributions to medical science did not end there. Far from it. He also discovered the Rhesus blood group system, responsible for haemolytic disease of the new-born, as well as demonstrating that polio was caused by an infectious organism. It was this latter discovery which lead to the production of polio vaccines and the almost total eradication of this terrible paralysing disease of children and young adults.

          I will now return to our womens' magazine and its perversion of Landsteiner's legacy. The magazine that published this article was targeted at young, upwardly mobile, professional women. Surely, I thought, some of its readers would be medical practitioners and write to object. None did - or at least, none of their letters were published. A possible explanation for the lack of indignation came from a survey recently published by the Medical Journal of Australia. It seems that at least 50% of Australian general practitioners believe in the efficacy of fairy magic like osteopathy, naturopathy, homeopathy, aromatherapy and reflexology.

          "And what's wrong with that?" you may ask. After all, Sir Arthur Conan Doyle, creator of Sherlock Holmes and himself a medical practitioner, believed in fairies. Well, what's wrong with it is that times have changed since the turn of the 19th century - which brings me back to Flanders and Swann.

          Michael Flanders appears in a wheel chair on the record sleeve because he contracted polio while he was in the navy during the Second World War. Polio was the disease that Landsteiner showed was transmitted by a virus, paving the way to the development of the cheap and effective vaccine that we now have. These days, there isn’t any reason why people should continue to be crippled by polio. And they won't be. But only if medical practitioners and their patients can understand the difference between the fundamentals of medical biology and the felonious fairy dust of pseudo scientific cargo cults.

Robyn Williams:
          The choice then is ours.

          Alan Baxter, on the centenary of blood groups, and the remarkable contributions of Dr Karl Landsteiner. Dr Baxter's book on immunology is called 'Germ Warfare' and it's published here by Allen & Unwin; lots of fascinating stories and gripping reading, too. Dr Baxter is Head of the Autoimmunity Group at the Centenary Institute in Sydney.

          Next week, David Yencken from Melbourne presents an Ockham's Razor about Australia's environmental future. I'm Robyn Williams.

'Michael Flanders, Karl Landsteiner and a Belief in Fairies' is © Alan G Baxter 2000


Autoimmunity Research Group, Centenary Institute of Cancer Medicine and Cell Biology, Key words: Autoimmune diabetes, Type 1 diabetes mellitus, childhood diabetes, lupus, systemic lupus erythematosus, hemolytic anaemia, hemolytic anemia, Coombs' test, antinuclear antibodies, renal failure, glomerulonephritis, gastritis, type A gastritis, pernicious anemia, immunology, popular science, biology.