What you don’t know about your blood
How is it that they had to call on a métis woman in Alberta to save the life of a baby in California? And that only five known families in the world share one blood group? Can a transfusion prevent cerebral palsy? The answers all say your lifestream is anything but simple
ON THE eastern slope of the Canadian Rockies April can be a kind month, a time of melting snows and the promise of summer. It was like that last April 27 -on the ground. In the air, the tardy winter was doing its best to kill an unborn baby thousands of miles away in Redwood City, California.
In a T-33 jet trainer, Lieut.-Commander Alan Wood, of the Royal Canadian Navy, and Flight-Lieut. Howard Robertson, of the Royal Canadian Air Force, ran into icing conditions soon after they took off from Edmonton. They were forced down at Calgary. But they went on, l>ecause they had to—their cargo was irreplaceable. Aboard were two bottles of one of the rarest types of human blood in the world.
To get it, a Canadian Red Cross doctor and a nurse from the federal Indian Health Services had already battled over almost impassable mud-bound roads, first in an automobile and then in a hay wagon pulled by straining horses. It took them a whole day to reach a donor thirty-six miles from Edmonton and return with one bottle. The second bottle took another all-day journey to the tiny village of Marlboro, on the way to Jasper Park. Then the blood had to be put through a series of tests that couldn’t be rushed. Precautions had to be taken against freezing in flight, and special packing had to be devised so the fluid could be flown in the thin air at thirty-five thousand feet without bursting the bottles.
Somehow it was done in time. In spite of the treacherous end-of-Apri! weather, the Canadian jet screamed down to a final safe landing at San Francisco. And on May 6 a baby girl was delivered by Caesarean section to Mrs. Nadine Robertson in Redwood City. A few hours later she received a transfusion of her mother’s blood which had been especially treated to remove dangerous antibodies. There were two more transfusions, using the hlood flown from Alberta. By May 12 it was certain that six-day-old Denise Louise Robertson would not only live, but would be a normal baby.
Only twelve years ago Denise would probably have died soon after birth. No one would have known why, although a “cause of death” would have been entered in the official record. Five years ago she would also probably have died. This time doctors might have
known why, but they couldn’t have done much about it. Because Mrs. Robertson’s blood contains such an unusual combination of the recently discovered Rh antibodies that until last year only four or five persons in the world—none in North America —were known to have hlood that could be added to hers without causing a violent and probably fatal reaction.
Her case and others like it have heljjed to change our whole idea of blood. Only fifty years ago even medical scientists thought it was a simple everyday fluid in which red and white corpuscles floated around. It kept us alive by carrying nourishment and oxygen to various parts of the body and carrying waste away. Everyone had it it was the same in everyone.
But now we know that blood is not at all simple: on the contrary, it is a maddeningly complex fluid which science has only begun to understand. It is not the same in everyone of course: there are four main blood types (A, B, AB and O), but more than three hundred thousand combinations can be counted. And it goes much further than that —how much further, nobody knows. Blood groups have been related to some of the spastic afflictions suffered by some children. Experiments have tried to link certain hlood groups with cancer, but without conclusive results. They are even thought by some to be influenced by cosmic rays from outer space through the genes which govern every human characteristic and function.
Whatever the answers to these mysteries concerning our blood, scientists are finding that the deeper they look, the less they know. Paradoxically, their work has been so successful that blood transfusions save tens of thousands of lives every year, as in the case of the Robertson baby in Redwood City.
The problem of the Robertson couple was fairly common one parent’s blood was typed as Rhpositive, the other as /¿/i-negative. In about one couple in twenty of such parents, drastic measures may be called for if the baby is to live. The trouble occurs when the child inherits a blood type from the father different to that of the mother and when the mother’s blood, as a result of previous childbirth or a former blood transfusion, has been stimulated into forming “antibodies.” During the last half of pregnancy these antibodies Continued on page 90
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What You Don’t Know About Your Blood
CONTINUED FROM PAGE 19
sometimes cross over from the mother’s circulatory system to the baby’s, where they begin destroying the vital red corpuscles of the baby’s own blood. The remedy is to give a massive "exchange” transfusion immediately after birth, in which almost all of the baby’s blood is withdrawn and replaced by blood of the mother’s type, so it won’t bedestroyed by the maternal antibodies.
Luckily for the Robertsons, Red Cross doctors last year came across twenty-one unknown possessors of the rare blood type the Robertson baby needed. All are métis living near Edmonton, and all are closely related. The long chain of heredity that produced the unusual blood stretches back to the chance migration of a single Iroquois brave around 1800 from a village near Montreal to the west. This, plus the other accidents of history and fate, led to a unique mingling of Iroquois, Cree, French and Scottish blood which in the twenty-one cases so far discovered completely lacks two of the mysterious, heredity-determined Rh antigens found in the blood of nearly everyone else in the world.
The complicated feat of identifying it—and the gift of life for a little girl— are only two of the latest triumphs by researchers. Their branch of science, which really began to make progress barely fifty years ago, achieved a spectacular break-through with the identification of the Rh factor in the early 1940s. This has enabled physicians to save thousands of infant and adult lives. It has prevented uncounted cases of cerebral palsy which transforms a child into an almost helpless invalid. It has given normal growth to children who otherwise might have been doomed to near-idiocy had they lived. And it has given at least the suggestion that tendencies toward certain ailments may be blueprinted on our blood cells from the moment we are conceived. All these discoveries have opened up further avenues of research.
As a result of this research oncehopeless ailments can sometimes be corrected with sureness and ease by blood transfusions. In Victoria, B.C., a housewife in her early forties had born four healthy children but had long suffered from repeated, dangerous internal bleeding. Two years ago her doctor recommended a hysterectomy—the surgical removal of the affected reproductive organs. Before the operation the patient’s blood was tested for its supply of red corpuscles. The "red count” in this case was low—drained away by the condition the operation was intended to correct. But that was routine—with a routine solution: just give a transfusion to bring the "red count” up again.
But for this Victoria mother the routine answer didn’t work. After the transfusion she had chill and fever, plus a mild jaundice, and there was no increase in the "red count.” She was still no better after a second transfusion.
At this point her doctor called in the Red Cross transfusion service. A sample of the woman’s blood was sent to Vancouver to be tested for all nine of the known systems that ordinarily make one blood different from another. The woman had been receiving blood transfusions from time to time for nineteen years and tests revealed that somewhere along the line she had been given blood from a person with a set of antigens in his blood exactly opposite
to hers. Everyone has a particular set of antigens in his blood, called the Duffy system, which infrequently complicates transfusions.
In the Victoria housewife the meeting of these opposite antigens had set up what scientists call an "immune reaction.” The blood "resents” the intrusion of a strange factor and begins manufacturing substances to destroy it; this is roughly what happens when the body fights a germ infection. These are called antibodies—anti-/?/?, antiDuffy or whatever the offending factor may be. They often remain in the blood for years; if the factor that first brought them into being is again introduced, the red corpuscles in transfused blood may be destroyed in the ensuing fight.
This was what was happening to the ailing housewife. Even after the menacing factor was identified as one of the Duffy antigens, her case wasn’t easy. She also happened to be Rhnegative, which ruled out eighty-five percent of all possible blood donors at the start. Somewhere among the fifteen percent of Victoria or Vancouver people who, like the patient, were /¿/i-negative, one had to be found whose blood was also compatible in Duffy factors. It took a lot of trying, but the right blood was obtained. The operation was a success.
You Don’t Mix With Animals
Finding how to unlock such mysteries of the blood cells has taken medical science three centuries, but the first two and a half were spent wandering up the blind alleys of ignorance and scientific dogma. The first reported attempt at a transfusion with human blood dates from 1654. A few years later a Frenchman described how he had given a transfusion of lambs’ blood to a fifteen-year-old boy with great success. For the next half century transfusions of lambs’ and calves’ blood were an accepted part of the physicians’ repertory. Then, when it became widely evident that more patients languished and/or died than got better, such transfusions fell into disrepute.
It wasn’t until 1875 that a French scientist named Landois noticed what actually does happen if you mix the blood of different species of mammals. In nearly every case the red corpuscles gather at once into lifeless clumps. Landois quickly determined that the substance causing this agglutination is in the fluid part, or serum, of the blood. The work of the great microbe hunters was already well known, so that scientists immediately recognized the clumping as an "immune reaction” like the ones they had previously observed with bacteria. And that ended attempts to cure suffering humanity with animal blood.
Unfortunately, people had a baffling habit of becoming violently ill or dying after human blood transfusions too. Further light didn’t break until 1900, and when it did come it was just a passing mention in a technical paper with a German title. Motivated by the divine curiosity that stirs scientists into historic discoveries, Dr. Karl Landsteiner, the paper’s author, began by asking six of his friends if he could have samples of their blood.
Landsteiner carefully separated the corpuscles from the serum in each sample. Then he remixed the six lots of corpuscles with the serums in all possible combinations. In some cases, he found, the red cells promptly fell into the familiar ugly clumps. But in others they continued to float happily and normally as individuals. In the patient tradition of research, Landsteiner tabulated the results opposite
the details of each mixture. Then he sat down to think out an explanation.
What he had discovered—as a Nobel Prize recognized thirty years later— was the fundamental division of all human blood into three main types, with a fourth which is a combination of two of the others. His experiment has meant that a human life can be saved by a single transfusion or—in the case of a woman in Camrose, Alta.—by one hundred and thirty-seven transfusions given over four years. His type names are still in use—the terse, A, B, AB or O that appears on army identification disks or on blood-donor cards in your purse or wallet.
The trouble earlier doctors had with their hit - and - miss transfusions of human blood is explained by the fact that we develop soon after birth certain serum antibodies which fight the invasion of a foreign blood group. Thus a person with A blood has antibodies that will destroy B blood, and vice versa. In a transfusion the serum of one blood attacks the corpuscles of the other. The victim gets chills, fever and the symptoms of jaundice. But the worst effect is the strain on organs such as the kidneys which try to get rid of the clumps of red cells. If the load is too heavy the patient dies.
On the other hand, O blood often can be transfused to other types with perfect safety. For a long time people with O blood were believed to be "universal donors.” Later experiments —some tragic—proved this a mistake. But O blood, which is also Rh negative, is sometimes unmatched when a transfusion must be given swiftly and the proper type of blood is not available.
No troubles are encountered in well over ninety-nine percent of the cases requiring transfusions, but it’s the other one percent that can cause dramatic transcontinental flights and have opened a whole new branch of human biology. After Landsteiner’s first discovery of the main blood types, it was found that there are also subgroups of these types, and that blood types are inherited.
What makes all this so remarkable is that blood groups are determined by tiny particles on the red cell surface— the expression of the genes, of which we inherit half from each parent. With such obvious features as blue or brown eyes, it’s pretty easy to look at a family and work out the hereditary pattern. But the genes themselves (which are also responsible for eye color) cannot be told apart even by the most powerful electron microscopes. All the blood researcher can do is make varying combinations of serums and corpuscles, and then sit down to think about them in the light of previously known facts or to suggest new interpre-
tations from his findings. It’s roughly the same method a blind man would have to use to find objects in a strange room—if you put boxing gloves on him before you let him in.
How well the researchers have done their job is demonstrated by the number of gene pairs they have identified. Thirty years ago anyone’s blood type would have been just one capital letter—unless he was group AB. Last month a Toronto doctor showed me the grouping card he now carries. It reads like this:—
O MNSs P+ Lu (a—) Le (a—. b + )
K— Fy(a—) Jk (a + , b—) CDe/CDe Saliva: secretor of H
Nine main group systems are commonly used, involving well over twice that number of genes, which can be arranged in thousands of combinations. In fact, the specialist blood group laboratory can now differentiate where necessary among 303,256 different hereditary gene patterns. Most of these are of little importance to a physician, since they don’t often affect transfusions. Some were first discovered because laboratory experts took advantage of the incompatibility of animal serums with human cells. The MN genes—or rather the "antigens” by which the genes make their presence known—were identified, for instance, using serum from rabbits. And the Rh groups (identified in the inset type above by the symbols CDe/CDe) got their name from the fact they were discovered in tests with rhesus monkeys.
What Makes a Backward Child?
This was the find that saved not only the Robertson baby in California, but countless others. Until it was identified, doctors had been baffled by a wellknown set of symptoms that preceded the death of a new-born baby in up to three percent of all infant fatalities. Such vague terms as "congenital anemia of the newborn” described the results while doing nothing to stop the massive destruction of red cells in the baby’s blood. Rh antibodies are now recognized not only as a common cause of these deaths, but also as one cause of cerebral palsy and other spastic conditions. In milder cases there can still be a devastating effect on some nerve tissue in the brain which, according to Dr. George Miller, of the Canadian Red Cross, "undoubtedly accounts for a lot of mental deficiency.”
"Every once in a while,” Miller points out, "you’ll find in a perfectly normal family a mentally retarded child. If you were to test that child, you might find his Rh type is different from the mother’s.”
Recent medical writing has tried to
alert all physicians to fairly common danger signals in childbirth—"mild neonatal jaundice,” for example. As a flat rule for minimum safety, Miller insists every pregnant woman should have an lih blood typing—a routine procedure with most obstetricians. About four hundred thousand mothers in Canada will have such a check this year hut—if past figures can be taken as a gauge—about sixty thousand others won’t. Aware of the perils that could befall this minority group, the Ontario government is the first to set up a free blood-typing service for such cases. Where there is an incompatibility between parents, the Red Cross will follow up with further tests for antibodies and with the right type of blood for transfusions.
Saving infant lives, while the most general achievement in blood research today, can be matched in many other branches of medicine. There’s a seven-year-old boy on the west coast, for instance, who is kept alive by a monthly visit to hospital for a transfusion. The victim of a rare blood ailment, he has to have his blood constantly replenished.
Even blood factors that never give clinical trouble often have a practical application. One is in determining paternity. Everything from the inheritance of a fortune to the suit of an unmarried mother for support of her child may depend on blood tests. There are eases where a mother is convinced her child has been switched with another in hospital, and there have been several where a child has turned up years after a kidnapping, in all of them, the blood group specialist has been called in to help establish identity.
The Case of a Jealous Husband
The only certain result of such blood j tests is to prove that a man could not j have been the father of a specific child, j The most that can be said on the other j side is that he may well have been the parent, along with all other men of his ! blood type. Usually, a positive blood j test is valuable only in support of other evidence. In some rare cases, however, fatherhood can be proved beyond all reasonable doubt, provided—according to one report by British researchers R. R. Race and Ruth Sanger—-"the I brothers of the accused have alibis.”
At the Hospital for Sick Children in I Toronto, Dr. W. L. Donohue says his department is called on for a paternity test once or twice a month. About a i third of the requests come from jealous husbands looking for evidence of a wife’s real or imagined infidelity. In nearly every case the wife’s honor is vindicated—unless the husband is prepared to believe that she coolly and thoughtfully selected a paramour of the same blood groups as his own.
! The opposite is also true. Most blood group laboratories have records of at least one case where a child could not apparently have been the offspring of j its legal father. The records are, of course, confidential.
These exhaustive tests are possible only in well-st ocked laboratories where a wide variety of antiserums of known types are kept. Every organization tries to make its collection as complete as possible, but the gathering of serums is partly a matter of chance. No laboratory knows on any morning what rare antibody may turn up in a routine blood sample by nightfall.
Some are so rare as to be unique. At least three cases have been reported ofobscure blood factors confined to a single family. Dr. Tom Brown, pathologist in the Wellesley division of the Toronto General Hospital, found himself in the thick of a case involving such a rarity last year. The patient, a
young housewife, needed a transfusion. To the consternation of the hospital lab, her serum promptly agglutinated every sample of blood to which it was added. Scores of cross-matches were tried, all with the same result. And though the hospital has lots of serums for typing, none could identify the factor responsible. Finally, a sample of the mysterious blood was sent to a Chicago laboratory, which went through the same depressing run of failures.
Then a Chicago doctor remembered a paper published in 1951 by Dr. Philip Levine, a leader in blood research whose laboratory is in New Jersey. It told the story of a sixty-six-year-old woman whose serum had agglutinated every one of the five thousand blood samples that Levine (obviously a patient man) had tried it on. Levine concluded that his subject had a previously unrecognized gene. Since then, only five families in the world had been found to possess it—one in Japan, one in Poland, others in three other countries.
Now, a sample of the Toronto patient’s blood was identified by Levine as a further example of the rare antiTja antibody. The process had taken months and, fortunately for the woman, her doctors had found a treatment that didn’t demand a transfusion. But the identification underlined a riddle that almost defies solution. It’s a bedrock assumption of science that genes are transmitted by heredity, and that accidental changes in them, or mutations, are the cause of new ones appearing. What causes the mutations no one really knows, although cosmic rays, atomic radiation and physical damage have all been suggested.
How then, does the same gene appear in families of three different races, scattered over the entire face of the globe, who are not known to be related to each other? Does the accidental lightning of mutation strike in exactly the same way at widely separated times and places? This is one of the problems that research seeks to solve. Doctors would also like to know whether there is any relation between blood types and the ailments people get.
In the case of the woman with the rare Tjb gene, it was thought there might be a link with the fact that she had cancer of the stomach. (The "T” in the name was chosen to stand for "tumor.”) But other Tj-genotypes turned out to be free of cancer. For a time, researchers tried to read significance into the high incidence of tuberculosis in the Alberta métis whose blood saved the Robertson baby in California. But Europeans with the same type of blood were apparently not abnormally susceptible to the disease.
There are some certainties, however, in the never-ending quest to solve the mysteries of our blood. Next year about 160,000 patients across Canada will need blood transfusions. The Red Cross alone will collect four hundred thousand pints from volunteer donors, of which a quarter of a million bottles at least will be used in transfusions of whole blood. The rest will be turned into serum albumin, gamma globulin and other needed blood fractions. Among those 160,000 cases, at least a few will challenge all the ingenuity of modern science to solve them. Any one of them may result in a spectacular hunt for a rare type of donor, and a dramatic dash to deliver the blood in time.
More dramatically still, any one of the blood samples collected could conceivably contain a unique and hithertounknown factor that would explain some of the still-unsolved riddles of heredity and medicine and lead to better health or a new cure. if