Dr. Thelin’s Fight Against Hemophilia

Dr. Thelin’s Fight Against Hemophilia

By PATRICA and RON DEUTSCH

Ten year-old Philip had a cold, and his life was in the balance. In his raw, swollen throat a few tiny blood vassals had broken.  In most of us, this common mishap would go unnoticed.  But Philip was a hemophiliac, a bleeder.  His blood would not clot, and the hemorrhage threatened to choke off his breathing.

To halt the previous bleed, doctors had transfused Philip with plasma—the clear liquid portion of blood.  But each pint contains only a small amount of the clotting factor his blood lacked and he had to be transfused day after day.  Again and again the doctors had had to stop, as the massive volume of plasma strained the capacity of the body’s circulatory system and vital organs.  Three times Philip faced death before they could begin transfusion again.  Only after four weeks did the bleeding end.

But this time the treatment was different.  Science had found a way to concentrate the clotting factor from over a gallon of blood [an adult’s entire supply] to a vial of white powder.  This was mixed with sterile water, and flowed into Philip’s veins.  Within hour his throat hemorrhage had stopped.

“For the world’s hemophiliacs,” said the late Dr. martin Rosenthal, former medical director of the national Hemophilia Foundation, “the concentrated promise a new life.  Now each small accident need not mean a desperate struggle to survive.”

To understand this achievement, it helps to know the story of Dr. Murray Thelin, for, though many researchers were involved, it was on this young biochemist that the final triumph centered.  And for him it had a double meaning: he, too, was a bleeder.  In serious form. Hemophilia—an inherited disease—of furs in one of every 10,000 males, prevalence roughly equal to that of polio before the Salk vaccine.  But until accident or surgery causes a bleed.

In 1961, Dr. Thelin jointed the highland Division of Baxter Laboratories in Los Angeles, to search for a concrete of the ant hemophilic factor—called AHF.  He was 34, a rather small man, pale from recurring blood loss.  His colleagues remember that he arrived with his right arm in a sling, impinge on his left leg and using a cane.  A few weeks latter they noticed that the sling was on the other arm and the limp in the other leg.  For, like most bleeders, he suffered badly from joint hemorrhages, cause deformities.  Murray’s legs had bled repeatedly since his infancy, and for years his main treatment had been bed rest and painkillers.

Patients of hemophiliacs go to great lengths to protect their children against injury.  Internal bleeds, not open wounds, are the worst threats, and a minor mishap may break a blood vessel anywhere in the body, including the brain.  Thus much of normal life may be denied to homothetic youngsters.

But not young Murray Thelin, born in 1972 on a farm in western Canada/ Murray tried everything.   He became an Eagle Scout, passing every test fairly.  When he had to spend weeks in bed waiting for bleeds to stop, he taught himself to play the saxophone and formed a band; he became a champion model maker. But above all, he dreamed of doing something for bleeders.

The Thelins were determined that Murray should have his chance.  When he was 19, they sold their farm and moved to Seattle, where Murray began a premedical course at the University of Washington.  Getting a job with a blood bank, he worked his way through.  It took him five years, and at the end there was disappointment; medical schools refused him, saying he could not take the stress of training.  Murray turned to blood chemistry.  In three years, still working his way though, he had his master’s degree and began studying for a doctorate at the University of North Carolina, under Dr. K.M.Brinkhous, renowned authority in the field of hematology, and Dr. Robert Sangner, a biochemist.

Brinkhous had given much hope to bleeders, for his work had made transfusions far more practical as a way to build up the clotting factor in emergencies.  He had discovered that the AHF was in the plasma, thus eliminating the need for whole blood transfusions with the attendant risk of red blood cells accumulating in the patient’s blood in such quantities as to cause dire reactions.  Brinkhous learned that plasma with its lifesaving AHF could be frozen and stored for emergencies.  Since plasma doesn’t have to be typed, bleeders now could be treated without a frantic search for donors.  Still, the problem of volume remained.  Brinkhous sought a way to concentrate the AHF, but every known means of removing the fluid also destroyed the delicate protein.

Then in 1957, Dr. Wagner suggested that an amino acid—a substance from which proteins are made—might bond to AHF without damaging it.  Some amino acids proved to be gentle enough agents to separate the AHF from the plasma.  The researchers at Chapel Hill tested the AHF concentrates prepared from human plasma.

Meanwhile, Stanford University’s Dr. judity Pool, working on a potency test for AHF-bearing plasma, made a strange observation.  Knowing how quickly AHF breaks down, she wondered how much was lost during the 40-odd minutes it took to transfuse a pint of plasma.  She tested a sample of plasma from the start of a transfusion, and one from the end of the procedure.  To her surprise, the sample at the end was not weaker but far stronger.

Months passed before she fully understood why.  Frozen plasma, thawed for use, was not completely clear: it had a few white flecks of protein floating in it.  In transfusion a filter in the plasma bottle screened these out.

Then a fussy lab man decided to centrifuge the plasma to remove the flecks.  When Dr. Pool tested this sample, it was surprisingly weak.  At once she suspected that the precious AHF was in the white sludge.

Clearly, under ordinary circumstances, some AHF dissolved during the transfusion.  But woven them some remained trapped by the filter.  Was this a road to concentrate?  To find out, highland laboratories hired Murray Thelin.

At first Thelin found only more problems.  To preserve the AHF, which loses its potency at room temperatures, Murray conducted his studies in temperature close to freezing.  The cold did his joints no good.  He had bleeds in his knees, ankles, hips, nose and tongue, and was in pain more often than not.  Until this time, he had kept up his outside activities—fishing, serving as a scout leader and as a Mormon elder.  Now he devoted every hour he was well to the lab.

By 1964, Murray, working with Dr. Edward Shabrom, medical director of highland, was close to accomplishing what many believed impossible.  Now, after hundreds of tests, they found a way to use an amino acid to gather AHF from the protein sludge.

The result was not pure AHF, but it was highly concentrated.  And Murray managed to dry this to a powder that dissolved in water.  He was just beginning to test the effect of his powder, when the worst happened.  Murray suffered a brain hemorrhage.

Rarely, if ever, had a hemophiliac survived much a hemorrhage.  Plasma would take effect too slowly to save him.  Murray’s only hope was his own untested concentrate.  Yet the concentrate might well cause fever of violent allergic reactions; even ordinary plasma made Murray break out in a bad rush.  Murray and Dr. shanbrom had no choice but to take the risk.  And Murray, though badly blurred speech, helped give instructions to the lab and laid out a program of tests on him to observe the drug’s effect.

Then came the first transfusion.  Murray’s clotting levels soared.  There was no untoward reaction.  In ten days he walked out of the hospital, smiling.  And now he speeded his efforts to learn how to produce the powder in quantity.

Tragedy threatened again.  Murray began to bleed from a peptic ulcer, usually a death warrant for a hemophiliac.  Once more his concentrate worked, quickly, safely.

Still the experts raised questions.  How would repeated doses affect a bleeder over a period of time?  Murray made himself a guinea pig.

Both he and Dr.Dhanbrom felt that his tests might answer a bigger question; could regular injections prevent bleeding?  Shanbrom administered the powder daily, and then found that weekly doses were enough.  The results seemed miraculous: weeks passed without a bleed.  Yet hemophiliacs, for unknown reasons, go through cycles of bleeding or not bleeding.  Was the concentrate really working?

The answer came when Murray went through a bad auto crash without a bleed.  Yet when the concentrate was deliberately withheld, he blew at a slightest provocation.  Clearly, the drug was protecting him.

When the concentrate was released to physicians for testing, success stories rapidly mounted.  A six-year old Chicago boy had bitten his tongue, and for five weeks the bleeding would not stop.  Two vials of the powder and the episode were over.  In New York a hemophiliac had suffered for months with chromic appendicitis.  With the concentrate, his doctors decided to risk removing the appendix.  “The operation was nearly as simple as if the man had been normal,” they said.  In Boston, surgeons at Tufts University have performed major operations on the spleen and brain of two hemophilic patients.  They both came through in fine shape.

Then, as the supply of the concentrate began to grow, doctors tried applying it to such common bleeder problems as tooth extraction.  Most important, because the concentrate can be used to stop joint bleeds quickly, before permanent tissue damage can occur, it offers the hope of preventing crippled joints. Says a doctor at Stanford, “We believe today’s hemophilic youngsters have every chance of growing up with straight limbs.”

The AHF concentrate is now widely available, and many hemophiliacs are able to treat themselves at the onset of a bleed.

More recent discoveries offer hope for the few bleeders who are not helped by the commoner concentrates.  While most hemophiliacs are different in the clotting protein called Factor VIII, about 15 percent lack Factor IX or X.  These factors were concentrated experimentally by Dr. James Tulles of Boston’s Protein Foundation and New England Deaconess Hospital, and are now commercially available.  Some problems remain to be solved, and research is focusing on ways to bypass the action of patients’ antibodies, which sometimes limits the usefulness of the new medications.

Murray Thelin is not directing this project.  In November of 1967 his heart suddenly gave out.  He was 39.

A month later Hyland laboratories accepted an award from the Hemophilia Foundation, for Murray’s work and that of Dr.Shanbrom on the concentrate.  “I wished that Murray had been there,” Dr.Shabbrom says.  “But he died knowing that in many ways, in his fight against hemophilia, he had won.”