In Warrenton, Va., a 14-month-old infant named Richard Jason Oliver died last year of Acquired Immune
Deficiency Syndrome (AIDS)—an affliction that most people at the time associated almost exclusively with male homosexuals. In the respected New England Journal of Medicine his doctor said that Jason had contracted the virus from two blood transfusions which he had received after his premature birth. Since then, 98 other AIDS-related fatalities—two of them in Canada—have been attributed to transfusions of contaminated blood on the continent and have produced increasing fears about the safety of blood transfusions. But now a Toronto biochemist has developed a procedure that may ultimately eliminate the major risks of transfusions —not only from AIDS but from other viral infections and accidental mismatching of blood types.
Maclean’s has learned that late last month the Canadian Department of National Defence filed a patent on a new purification procedure for hemoglobin and modified hemoglobin solutions which appear to greatly reduce the dangers traditionally associated with those substances when used as blood substitutes. Developed in the department’s Toronto laboratories by 46-year-old biochemist Carleton Hsia, the procedure has not yet been fully tested. But if proved effective, it could have a farreaching impact.
The concern over blood supplies contaminated by the AIDS virus has added new urgency to the long quest for what medical researchers refer to as a blood substitute: an alternative to whole blood—the mixture of red cells, white cells and plasma which has become central to current medical practice. Indeed, one Toronto surgeon, who refused to be identified, admitted that for some operations he no longer routinely “tops up” a patient’s blood with a transfusion. And Dr. Gerald Growe, director of the blood bank at Vancouver General Hospital, reported calls from colleagues asking whether they should postpone elective surgery until after the Canadian Red Cross institutes a test to screen out antibodies to the AIDS virus in donated blood this September—six months after it was introduced into most American blood banks. But in fact the test is not 100-per-cent effective.
Hsia’s purification method of a modified hemoglobin blood substitute ap-
pears to eliminate those problems. But until further testing on animals is completed over the next three months, the defence department has declined to elaborate on Hsia’s findings. Said Manny Radomski, chief of the department’s Defence and Civil Institute of Environmental Medicine: “It is just too premature. We do not want to fall flat on our face.” But Radomski said that if Hsia’s method can be reproduced and tested to satisfaction, it does have “ex-
citing potential” for a sizable portion of the nearly four million North Americans who need blood transfusions or blood products each year. Among other things, it would eliminate the complex and costly problem of matching blood types, as well as the often-fatal consequences of transfusing mismatched blood. And it could dramatically extend the shelf life of transfusable blood, which blood banks must now discard after 35 days.
Hsia (pronounced Shaw) says that if his purification procedure proves to be sound, it would be a relatively simple next step to filter out the viruses that produce such diseases as hepatitis and AIDS. And he theorizes that ultimately the solution could be freeze-dried like instant coffee—a dream of blood researchers for four decades. But those possibilities remain theoretical. For his part, Dr. Robert Valeri, director of the U.S. Naval Blood Research Laboratory in Boston, who has tested Hsia’s hemoglobin solutions, says that it is too early to make any sweeping claims for the solution. But, he added, “The preliminary results are very exciting.” De-
clared Robert Geyer, chairman of the department of nutrition at Harvard University’s Graduate School of Public Health in Boston: “A blood substitute could be used in an emergency where you would not have the facilities to worry about blood-typing—in a military setting or a mass disaster. If it works, it would represent a real breakthrough.” Defence departments have led the way in blood-substitute research, which began in earnest after the Second World War. For the military, the costly and cumbersome problem of transporting refrigerated blood to the battlefield is a logistical nightmare. But research swiftly split into two competing camps. One focused on substituting lost blood with fluorocarbons—synthetic chemicals related to the cooling agent used in refrigerators. One of those chemicals, manufactured by the Japanese Green Cross Corp. as Fluosol DA, has been tested on humans in Japan and on a handful of American Jehovah’s Wit-
nesses who refused blood tranfusions.
But the American Food and Drug Administration recently denied licence approval for Fluosol, saying that it had not proven its ability to transport oxygen more efficiently than a simple salt solution. And to remain effective Fluosol must be kept refrigerated and administered in the presence of 100-per-cent oxygen. Said Dr. Robert Bolin, former director of the U.S. Army’s blood substitute research program: “We cannot put oxygen and a freezer in the field.”
A competing school of researchers has concentrated on transfusing only hemoglobin —the oxygen-carrying
molecules isolated from red blood cells. Indeed, in discovering a method of freeing hemoglobin from the red-cell membrane, biochemists also found that they had eliminated the problems of bloodtyping because the antigens that cause blood incompatibility are coded on the walls of the red-cell membranes, called stroma. But other problems made that breakthrough irrelevant: the brokendown cell membranes and the debris that remained in those hemoglobin solutions clogged up the kidneys, causing renal damage and sometimes outright kidney failure. In addition, the solutions swept through circulatory systems into the urine too rapidly and largely failed to perform their primary task—delivering oxygen to body cells.
In the past two decades scientists have prolonged the solutions’ stay in the bloodstream by stabilizing them with polymerization, which strings the hemoglobin molecules together in large clusters. And chemically modifying
them with a variety of phosphate compounds has improved their efficiency in delivering oxygen needed to repair damaged tissues. But after Valeri had tested a range of those new modified hemoglobin solutions from laboratories across the continent, he found that they all registered one serious side-effect: they produced dangerous contractions of the vessels in the hearts of the rabbits upon which he had experimented.
Hsia, a Chinese-born scientist who was initially involved only in contracting others to carry out blood substitute research for the defence department, theorized that because the hemoglobin could never be modified completely, the unmodified hemoglobin may have been responsible for producing the constrictions. Taking on the task himself two years ago, he used affinity chromatography, a technique that locks a specific molecule onto the remaining unmodified hemoglobin exclusively to remove it from the test solutions.
When Valeri completed his first series of experiments with Hsia’s samples in April, he found that it drastically reduced vessel constriction. But the defence department and Valeri both say that such results must be repeated before tests are tried on whole animals and eventually humans. Said Geyer: “The question now is whether this can be reproduced in sizable quantities for testing. That has been the main problem so far. As soon as people try to produce large batches of these kinds of solutions, for some reason it doesn’t work.”
Hsia says that because viral particles are larger than hemoglobin molecules, they could easily be filtered out to eliminate contamination by hepatitis and AIDS. But that, too, remains hypothetical. The chief advantage of an effective hemoglobin solution would be to eliminate the danger of mismatching blood types, which currently occurs once in every 10,000 transfusions.
Valeri envisions keeping stocks of such a solution on hand at airports in case of plane crashes, as well as at other potential disaster sites. And because hemoglobin solutions are currently made from outdated red cells discarded by blood banks, they would effectively extend the life of donated blood. They would not, however, help hemophiliacs, whose need for the clotting agent known as Factor VIII—made up from platelets collected out of massive pools of donated blood—has made them one of the groups most susceptible to AIDS. Indeed, researchers emphasize that the promise of aviable blood substitute would in no way eliminate the need for the current blood donor system. Said Hsia: “We will never be able to replace the gods’ creation of our own red blood cells.”
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