The
Disease That Always Killed
By
GEORGE H. WHIPPLE, M.D., as told to J.D.RATCHLIFF
It was a pure horror of a disease.
It started innocently enough.
Victims noted that everyday chores tired them more than usual. Soon they were finding difficulty rising
from a chair. Their skin took on a
waxy, yellowish cast; tongues became flaming red and sore. Some sufferers became addle-headed; a few
went on to paralysis.
Pernicious anemia was a leisurely killer. It might take two to five years to claim its
victims. But, eventually, all
died. When they finally expired, blood
counts were often down from a normal five millions red cells per cubic
millimeter of blood to a watery 500,000—not enough to carry the needed amount
of oxygen around the body. Slowly,
tissues and organs were asphyxiated.
Physicians fought futile battles against this
doom. A mysterious poison was killing
some thought the red cells off. Others
made a better guess; that the bone marrow, which manufactures red cells, had,
for unknown reasons, forgotten how to produce the trillion new cells needed
each day. Still others believed that
the spleen played some role in the disease and that its surgical removal would
help. Such patients did well for a
while, and then began slipping again.
Whatever the treatment, the end result was always the same: death.
The conquest of this disease was, I believe, one of
the first instances in medical history in which a universally fatal illness was
converted into a minor inconvenience. Today,
tens of thousands of people live normally with pernicious anemia, scarcely
aware that they have it. Here is the
story of how this came about.
Both my grandfather and father had been country
doctors in New Hampshire, and I was tempted to follow in their footsteps. But, while studying at Johns Hopkins, I
became interested in pathology; the study of disease itself. Blood in general, and the anemias in
particular, fascinated me almost from the start. I studied the anemia, which accompanies hookworm disease, and
observed tropical anemia in Panama in 1907 while the Panama Canal was under
construction. Opportunity to get at the
problem in a concentrated way came in 1914, when I was invited to San Francisco
to head the new Hooper Foundation, the research arm of the University of
California’s Medical School.
The anemia, of course, is a wide spectrum of
diseases, and even in those days most of them were curable. But pernicious anemia was different. The normal lifespan of a red blood cell is
120 days. As each dies, it must be
replaced—ten million are needed each second.
In pernicious anemia the new cells were not produced in adequate
number. It seemed obvious to me that
the only source of building material for red cells was food, and I blocked out
a study along these lines.
The first step was to produce artificial anemia in
dogs. Form neck artery I intermittently
withdrew blood until the level of hemoglobin—the vital red coloring matter in
blood cells—was 40 to 50 percent below normal.
[The procedure, incidentally, did not seem to bother the animals at
all.] Then various diets were tried to
see which, if any, hastened production of new red cells.
At this point a compact, blond young woman appeared
in my lab and demanded a job.
German-born Frieda Robscheit—later she would Americanize her name to
Robbins—was absolutely determined. ‘I
am going to work with you, whether you like it or not,” she said. I hired her, and she turned out to be one of
the finest collaborators any researcher can ever had.
Our first problem was to devise a basal diet for our
dogs, one that would provide essential nourishment but would be the poorest
possible for building blood. Then we
would supplement this diet with various foods to see which would hasten
production of red cells.
Months, years, passed. Thousands of red-cells counts were made as the work crawled
methodically along. Scores of foods
were tried as blood builders—milk, eggs, lettuce, Naturally, we also tried a
variety of meats. A slaughterhouse near
the lab furnished whatever we required in this line; spleen, pancreas, bone
marrow, brains, sweetbreads. And in
time an extraordinary performer emerged.
It was liver in as little as two weeks liver restored low-red-cell dog
blood to normal. We found it difficult
to believe that any food could act with such speed and efficiency.
But our work was by no means completed. If liver was to be the hero in conquering
anemia, the fact had to be nailed solidly down—which meant trials on many more
dogs, with time of recovery exactly measured.
In 1921, I moved to Rochester, New York, to become
dean of a medical school then being started.
As soon as the new laboratory was ready, Frieda Robbins came east by
train, accompanied by our kennel.
Finally, in 1925, we felt confident enough to report: “Liver feeding
remains the most potent factor for the sustained production of hemoglobin and
red cells.” Now, somebody else had to
extend our findings to treatment of pernicious anemia in human.
Dr. George R. Minot of Hayward was one of the very
finest in Boston medicine. Tall,
rail-thin, fastidious, reserved, he was totally dedicated to his patients. When he heard of our work on dogs he
determined to try liver on his pernicious anemia cases.
Not at all well himself—he suffered from diabetes—he
enlisted the help of a younger colleague, dr. William P.murphy, then at Peter
Brigham Hospital. The two almost
literally stuffed their patients with all the liver they could get down
protesting gullets. Sometimes Murphy
mixed ground raw liver with orange juice and poured this in. Patients in a coma got ground liver via
stomach tube.
The response was almost beyond belief. Within a few days, patients looked better,
felt well, and their red-cell counts were climbing. May be these people weren’t doomed after all!
On May 4, 1926, Minot, in his flat New England
voice, read a paper before his peers at the annual meeting of the Association
of American Physicians. He reported
that he and Bill Murphy had stuffed 45 patients with liver. Some had had blood counts lower than on
million, now all but one had near normal counts. That one was an elderly lady who so despised liver that she said
she preferred death to eating it. Most
of the other patients were up and about—no longer breathless, no longer
weary. Most were back at normal
occupations. Minot’s report was
acclaimed by a standing ovation.
Ata hospital in Boston next morning, doctors were
preparing to give an elderly man a transfusion—the only thing that had kept him
barely alive for several years. “Why not
just let me die?” the weary sufferer asked.
A young doctor burst in. “Did
you see the morning paper?” he asked. A
news report had summarized Minot’s paper.
Liver diet was started immediately, and within a week the patient had
new life in his limbs.
Such events were soon being enacted all over the
world. A year later, Minot and Murphy
reported on 105 patients. There had
been three deaths: one in an auto accident, one from cerebral thrombosis, one
from unknown causes—but none from pernicious anemia.
In 1934, Minot, Murphy and I received identical
cablegrams from Stockholm. We had been
accorded medicine’s highest honor, the Nobel Prize.
A way had been found to rescue the doomed—but the
story was still by no means complete.
Even at outset it was clear that it wasn’t liver that was working such
wonders, but some elusive X substance in liver. The problem was to get rid of useless components and concentrate
on the substance. Dr. Edwin J. Cohn,
the gifted Howard chemist, took this job upon himself. Soon he had an extract, one tablespoon of
which was the equivalent of half a pound of liver. Next came an injectable liver extract 400,000 times as potent as
the mother stuff; a short every two to four weeks was sufficient to keep blood
normal.
The search for the X substance came to an end at
last in 1948, with the cornering of Vitamin B12. An invisibly small amount of it—a millionth of a gram a day—was
sufficient to control a disease once totally deadly.
Pernicious anemia,
which had probably plagued man from the beginning, at last could be rendered
harmless.
