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The Nobel Prize in Physiology or Medicine 1934
George H. Whipple, George R. Minot, William P. Murphy
The Nobel Prize in Physiology or Medicine 1934
Nobel Prize Award Ceremony
George H. Whipple
George R. Minot
William P. Murphy
Award Ceremony Speech
Presentation Speech by Professor I. Holmgren, member of the Staff of Professors of the Royal Caroline Institute, on December 10, 1934
Your Majesty, Your Royal Highnesses, Ladies
and Gentlemen.
The Caroline Institute has awarded this year's prize for
Physiology or Medicine to three American investigators, viz.
Professor George Minot, of the Harvard Medical
School (Boston), Dr. William Murphy, of the same College, and
Professor George Whipple, of the School of
Medicine (Rochester, New York), in recognition of their
discoveries respecting liver therapy in anaemias. By anaemias is
to be understood diseases in which the patient is anaemic. The
medical man, in speaking of anaemia and anaemic, has not in mind
the actual quantity of the blood, which is not easily
determinable by simple methods, but rather certain shortcomings
in the composition of the blood that allow of being readily
established in his routine investigations, in the first place a
diminution in the number of the red blood corpuscles per
unit-volume of blood, and a diminution of the concentration in
the blood of the haemoglobin, i.e. of the red pigment that gives
the blood its colour, a diminution consequently in the
colour-strength of the blood. In a word, the blood has become
diluted.
Of the three prize-winners, it was Whipple who first occupied
himself with the investigations for which the prize has now been
awarded. He began in 1920 to study the influence of food on blood
regeneration, the re-building-up of the blood, in cases of
anaemia consequent upon loss of blood. For the fact is that
anaemia in the sense just mentioned also arises as a consequence
of a loss of blood. The diminution in the quantity of the blood
is made up for, comparatively quickly, by an influx of water from
the tissues, that is to say by a process of dilution, of which
the consequence is a reduction in the number of the red blood
corpuscles and the haemoglobin per unit of volume - thus a case
of anaemia. That being so, Whipple started to study the effect
that various food substances might have on the process of the
regeneration of the blood. It was known beforehand, it is true,
that a plentiful supply of food is an important factor in
restoring the blood to a normal consistency, but it was not known
that independent of the quantity of the food and of its caloric
value, different articles of food played differing parts. The
method Whipple adopted in his experiments was to bleed dogs, that
is to say to withdraw from them a certain quantity of their
blood, supplying them afterwards with food of various kinds. By
that method he discovered that certain kinds of food were
considerably superior to others, inasmuch as they gave stimulus
to a more vigorous reformation of blood, that is to say
stimulated the bone marrow - in which the blood corpuscles are
produced - to a more vigorous manufacture of red blood
corpuscles. It was first and foremost liver, then kidney, then
meat, and next after that certain vegetable articles of food too,
e.g. apricots, that proved in an especial degree to have a
strongly stimulating effect. Whipple's experiments were planned
exceedingly well and carried out very accurately, and
consequently their results can lay claim to absolute reliability.
These investigations and results of Whipple's gave Minot and
Murphy the idea, that an experiment could be made to see whether
favourable results might not also be obtained in the case of
pernicious anaemia, an anaemia of quite a different type, by
making use of foods of the kind that Whipple had found to yield
favourable results in his experiments regarding anaemia from loss
of blood.
Before entering upon a discussion of Minot's and Murphy's
investigations in detail, I propose to say a little about
pernicious anaemia. As the name tells us, it is a fateful
disease, which, previous to the labours of our prize-winners,
almost invariably, with only very few exceptions, ended fatally
in the course of a few years, or in a still shorter time, a few
months. Its cause is not known. It customarily makes its
appearance in middle-aged persons, who lose colour, feel tired,
and ultimately consult a doctor, who establishes the fact that
their red blood corpuscles have become reduced in number from the
normal figure of about five million per mm3 to considerably lower values, e.g. one million
per mm3, or to still less,
eight, seven or six hundred thousand per mm3, and that the colour-strength of the blood has
also diminished, though as a rule not in the same high degree as
the number of the red blood corpuscles. Moreover, on examining
the blood microscopically, the investigator finds that the red
blood corpuscles in it are very different to normal red blood
corpuscles. The latter are all alike in size and in form, whereas
in pernicious anaemia there are to be noticed blood corpuscles of
a great variety of sizes, some considerably larger than normal
and some small ones; and their shapes vary too. They are diseased
or immature forms of red blood corpuscles. Hence what the bone
marrow has supplied to the blood is not of a completely
satisfactory make or consistency. The course of the disease is
customarily a cyclical one, periods of specially severe anaemia
alternating with periods when the composition of the blood is
more normal. The circumstance that the disease itself is subject
to variations, showing now improvement, now relapses, renders it
of course very much more difficult to determine the actual effect
produced by any treatment administered to the patient. Previous
to the results of Minot's and Murphy's experiments the principal
mode of treatment adopted, and one that was practised all over
the world, was the giving of large doses of arsenic, while in
serious cases it was also customary sometimes to resort to
splenectomy, that is to say to removal of the spleen by an
operation, or to blood transfusion, i.e. the transfer to the
patient of blood from another person, a method that is still to
be recommended at a critical stage in severe cases. Hence it was
quite a strange conception, and one lying remote from the
customary beat, that came into the minds of Minot and Murphy,
when they bethought themselves, that it might possibly be
feasible to treat a patient suffering from this disease by
administering food to him. It was an idea, in fact, that
had never been conceived of, up to that time. A consultation of
the textbooks with regard to the matter, for instance, will show
us that very little attention was paid to the diet. Some items of
good advice are to be found given, indeed, respecting the
patient's diet in pernicious anaemia, not as an integral part of
the treatment though, but rather as an element in the nursing
required in general. There was, however, one exception to that
universal rule, for in one spot in the world the idea had really
arisen and been put into practice. To that I shall return later
on.
The first work published by Minot and Murphy in regard to this
question dates from 1926. It was a short paper of nineteen pages,
entitled: «Treatment of Pernicious Anaemia with a Special
Diet». No mention here of a liver diet, but of a
special diet, the special diet they had in view being one
derived from Whipple's investigations, based on Whipple's diet,
consisting of liver, kidney, meat and vegetables, the last two
also in large quantities. As reports of observations began to
come flooding in, showing that results had really been achieved
by the application of the diet, there occurred by degrees a
variation in the composition of the dietary in favour of liver,
that food substance which, according to the showing of Whipple's
investigations, had the strongest stimulating effect upon the
erythropoietic, red-corpuscle forming function of the bone
marrow. In their later publications we see, moreover, that they
employ the designation: «a diet rich in liver». Hence
their diet became more and more preponderatingly a liver diet.
There were, it is clear, great difficulties in the way to prevent
their arriving at any real discovery in this regard, for the fact
is, as we know, that in order to be able to achieve any palpable
results from a liver diet, it is requisite for the patient to
have liver administered in very considerable quantities every
day, in quantities running to three, four, five, or six hundred
grams, or even still more, per diem - consequently, in the
twenty-four hours, upwards of half a kilogram of liver, either in
a raw state or in some cooked form. We can understand what
obstacles that presented for the successful issue of the inquiry,
since such quantities of liver seemed very outrageous at that
juncture, when there were no particularly strong reasons for
expecting that the diet would have any important influence on a
sufferer from pernicious anaemia. The opinion held respecting
pernicious anaemia was, that it was so essentially different in
nature to the blood-loss anaemia, that there did not exist, from
a therapeutic point of view, any real reason for combining them
together at all. As consequently there was nothing that could
with any degree of certainty be expected to result from the
application of the diet in question, and as the method of
treatment demanded such unreasonably large quantities, it is
clear that the experimenters must of necessity have been
possessed of an extraordinary measure of far-sightedness, an
extraordinary degree of energy and an extraordinarily clear grasp
of all the circumstances of the case, as they were enabled to
succeed in inducing the patients to submit to such a regimen
notwithstanding its disagreeableness. If Minot and Murphy had not
been imbued with such an irresistible urge to bring matters to a
head, so to say, their discovery would never have been achieved.
It was found, however, that, on the diet being put
contemporaneously to the test at a large number of hospitals in
the United States, results were actually obtained from the
treatment that were astonishing, showing a more rapid improvement
and blood formation, i.e. a more complete restoration to normal
conditions, than had been seen to result from any other methods
of treatment. It was also by degrees observed that, when once
they had recovered a normal state of the blood, the patients
remained well in health, which had not been the case with the
methods previously applied, for with them, even in instances
where very considerable improvement occurred, there had been the
periodic relapses, which, as I mentioned before, are a
characteristic feature of the disease. No sooner had these
results been achieved in America, and been made public, than
liver diet began to be tested in all parts of the world as a cure
for pernicious anaemia, and from all quarters there came reports
of the same experiences as to results. From everywhere
confirmation came of Minot's and Murphy's observations being
correct.
The success of the treatment, i.e. that by administering liver
one could actually secure the disappearance of the symptoms of
pernicious anaemia, meant not only a great therapeutic triumph,
but also a reversal of the theory up to then held respecting the
nature of the disease. The former idea had been, as a fact, that
the essential point in the conditions predisposing to pernicious
anaemia was the presence in the organism of a poisonous agent, a
poison arising in one way or another or originating from one
quarter or another - ideas respecting that point were divergent,
but in general there was agreement that there must be some poison
that interfered with the proper functioning of the bone marrow,
entailing as a consequence the production on its part of
diseased, imperfect, immature red blood corpuscles. The discovery
that the disease could be cured by the sufferer from it being
given a diet of liver, led scientists, very naturally, at once to
query in their minds whether the theory regarding the disease
that had up to then been prevalent could be correct. Reflection
upon the matter must as a matter of course lead to the
conclusion, that it was not probable that the presence of
a supposed poisonous substance could be the cause of the
disease, it being seemingly due rather to the absence of a
substance that was requisite for a satisfactory production of
red blood corpuscles, a substance that must be present in liver,
seeing that the patient's condition became normal when liver was
supplied as a food. In fact, a new function of the liver had thus
been revealed. It is interesting to observe the reaction of
medical science to this altered aspect of the matter. There exist
certain representatives of quasi-medical or medico-religious
bodies, who are in the habit of alleging that medical science is
a species of religion or philosophical system, based upon
irrefrangible tenets that do not allow of alteration or
modification. That may have been so some hundreds of years ago,
but in our days it is so no longer. The framework of medical
science, as of other natural sciences, is a body of facts and
upon them medical theories are based and built up. When a new and
important fact has been established, the effect is somewhat like
that of a bomb falling to earth: those theories that do not admit
of being reconciled with it are exploded, being replaced at once
by others that can be brought into better harmony with the newly
acquired item of factual knowledge. And that has been the case in
the present instance.
With a view to affording a background against which the
discoveries of the prize-winners may stand out in stronger
relief, I propose to say a few words as to the function of the
liver in general. We are all aware that the function of the liver
is to secrete bile, to be discharged into the bowel. As is well
known, the bile is of great importance in aiding the process of
digestion. This function of the liver is termed its external
secretion, its products by degrees reaching the surface of the
body. Besides that, however, the liver has other functions; it
has for instance also a so-termed internal secretion. The first
fact respecting an internal secretion that science was able to
reveal to mankind bore reference actually to the liver, being the
discovery, made in 1855 by the great French physiologist Claude
Bernard, of the liver's glycogenic function, i.e. of the
important part played by the liver in the metabolism of sugar in
the body. On demand the liver supplies the sugar that the body
requires for its normal functioning. Claude Bernard gave that
process the name of «une sécrétion interne»,
thereby creating the term: «internal secretion», of
which we hear so much at the present day. Since his time the
theory that he first enunciated has been built up and amplified
very materially. Thus, it is known now, respecting a number of
glandular organs, that, in addition to any external secretion
that they may be capable of, they also possess an internal
secretion, that they consequently manufacture products that are
delivered directly into the blood, and which are subsequently
conveyed via the blood vessels, to remote parts of the body,
where in other organs they give rise to impulses, accomplish
effects, that are of the very greatest, indeed often of a vital,
importance for the body. To those products, which the internal
secretion supplies, the English physiologist Starling has given
the name of hormones. We are now acquainted with a very
considerable number of hormones. Time, however, does not admit of
my entering into the subject further; I will only call attention
in passing to the latterly so much discussed sexual hormones,
those hormones, that is to say, that regulate the sexual
functions, as to which in recent years especially Professor
Zondek has made such fundamental investigations. Further, I may
mention insulin, familiar to us all, a pancreas hormone, which
medical men make use of in the treatment of diabetes. When the
pancreas itself is incapable of producing this hormone, which is
an essential requisite of the body, diabetes establishes itself.
If under those circumstances the hormone is supplied to the body
by the injection of insulin, derived from the pancreas of some
animal, the symptoms of the disease can be kept away. This method
of treatment, which consists of making the patient, in whose body
some organ is not functioning satisfactorily, consume portions of
the said organ, or absorb by injection, preparations of the said
organ, is termed organotherapy. Another name is substitutional or
replacement therapy, since the method consists in making
substitution for, or replacing, the production that is wanting by
supplies from outside. That type of treatment is not so
absolutely new as many people may think. Thus, we may recall that
a French physiologist, Brown-Séquard, as long ago as 1889,
carried out investigations, which aroused great astonishment at
the time, as to the effect of an injection into the body of
testicular juice, got from the male genital glands. He gave
himself injections of testicular juice and observed considerable
rejuvenating effects both physically and mentally. That
constituted the first achievement in the direction in question
that science accomplished. Hence, it is Brown-Séquard who
laid the foundation of organotherapy, and the rejuvenation
treatments that we hear so much about at the present time, had
forerunners at an earlier date. In this particular case, as in
general in the field of medicine, it is seen that, by delving
into the ancient records of the cultural achievements of the
past, we may discover the nucleus of many of the methods that
attract so much attention in our own times as novel and
epoch-making. If we study Ebers, the papyrus of the ancient
Egyptians, a venerable documentary record of the world of many
thousand years ago, we shall find numerous evidences to show that
the ancient Egyptians made use of organotherapy. Owing, however,
to their defective knowledge of details they were unable to
secure such brilliant results or to carry on their labours so
purposefully, as, thanks to our incomparably greater knowledge,
we are now in a position to do.
On now examining, in the light of the above facts, the
discoveries made by our Nobel Prize winners, we thus find that
they have come upon a new, hitherto unknown internal secretory
function of the liver, have discovered that the liver yields a
substance that is of the utmost importance for the normal work of
the bone marrow in forming new blood.
The liver treatment for pernicious anaemia, which from its very
start showed itself to be of immense value, was as already said
not an easy or agreeable one for the patients to submit to, owing
to the large quantities of liver that they had to consume. Even
after the composition of the blood had been restored by the liver
treatment to a normal state, it was obligatory to make the
patients continue to eat large quantities of liver, in order to
keep up their recovered health. During the years that have
elapsed since then, the technique of the treatment has undergone
development: the active agent or stimulating substance in the
liver has been successfully extracted, an extract being thereby
obtained that contains the active substance in a more
concentrated form. Latterly the concentration has been brought
down to such small volume, that an injection of less than a gram
of the substance in solution proves a sufficient quantity for
maintaining the blood in a normal condition for a period of a
fortnight. Hence one injection a fortnight should suffice for
keeping such patients in a state of health. The fact of so small
quantities being found to be all-sufficient leads one to think of
the hormones to which I referred above, they being capable of
accomplishing very great results with very small quantities, and
one puts the query to oneself: Is it a hormone, this substance in
the liver that is made use of for curing pernicious anaemia? As
to that, it is not as yet quite decided what it would be most
correct to call it - a hormone, or a vitamin, or something else,
and I do not propose to enter upon a discussion of that here; it
may be that there are not essential differences either between
the various concepts named.
In the foregoing I mentioned the fact, that the idea of treating
pernicious anaemia by food had arisen in one quarter
previous to Minot's and Murphy's day. That quarter was Stockholm,
for the late Dr. Warfvinge, superintendent physician at the
Sabbatsberg Hospital, who died early in the present century, had
actually conceived the said idea. He was a very distinguished
clinician, specially interested in diseases of the blood, and he
used to urge with great emphasis that in cases of pernicious
anaemia the most essential thing was for the patients to eat
meat, meat in large quantities and at every meal, that
being more important than the administration of medicine or than
any other form of treatment. He was very insistent in urging it
upon his assistants at the hospital, that they should bring all
the influence of their authority to bear on the effort to induce
the patients to eat meat, to feed themselves up on it, to force
themselves to get down as large quantities of it as they possibly
could. What was that but a harbinger of the very treatment, to
the discoverers of which there has now been awarded the Nobel
Prize? Whipple's investigations have taught us that, next to
liver and kidney, meat is the article of our regimen that
exercises the greatest influence as a stimulus to the blood
regeneration carried on by the bone marrow. With his keen
clinical eye, Warfvinge had discerned that there was something of
special importance in meat, and consequently he placed in the
forefront of the treatment the item that the consumption of meat
constituted. It appeared to me that it would possess a certain
interest for those who are present here this evening to be
reminded of that circumstance.
What is then the significance of this new method of treatment? In
the first place there is the fact that, thanks to it, a sufferer
from pernicious anaemia can with tolerable certainty be rescued
from a premature death. Hence, for the individual, the method is
of an exceedingly great importance. Its importance in a wider
sense must of course be dependent on the seriousness of the
disease in its effect on the community at large, i.e. on the
relative frequency of cases of pernicious anaemia. It is in fact
quite a common disease, for in the United States, for instance,
it is estimated that, previous to 1926, the year in which Minot's
and Murphy's methods of treatment were first applied, about six
thousand persons died of pernicious anaemia every year. I have
calculated - very approximatively - that, since the date when
their methods began to be generally applied, some fifteen or
twenty thousand persons must have been saved from death in the
United States alone. As regards conditions in Stockholm, there
have been 450 cases of pernicious anaemia that have been treated
at the Serafimer Hospital since I became attached to it, while,
according to a recent estimate, in Sweden as a whole there must
be something like three thousand persons who are suffering at the
present time from pernicious anaemia. Hence the number of the
lives to be rescued year by year by the application of the new
method of treatment is quite considerable.
When medical progress in regard to the healing of diseases is on
the tapis, there is one objection that is not infrequently
brought up. People are apt to urge that, although it may be fine
and merciful to effect those cures, yet, from the point of view
of the community at large, it is not a thing to set much
store by or that is beneficial, since disease, being a
scavengering implement that Nature makes use of, clears off the
elements in the population that are of inferior value, and leaves
a residue that is of more vigorous stamina. That line of argument
would lead us to the conclusion that, from the point of view of
race improvement and race development, it is not to be considered
any advantage to rescue those who are afflicted with diseases
from which they cannot cure themselves. That reasoning is
specially prevalent with respect to epidemic diseases. It is
supposed by many people that, when such scourges beset a
population, the victims that are swept off are the weaker and
more delicate individuals, and that consequently, apart from the
humanitarian point of view, it is after all advantageous to the
community that the disease should run its course. That chain of
reasoning, however, is based upon ignorance of how matters stand
in reality. For it is not the case that, when an infectious
complaint sweeps over a populated area, it is the inferior
elements that are snatched away. Those victims that fall a prey
are not inferior in any other sense than in regard to their
powers of resistance to that particular virus or injurious agent
- in other respects they may very well be as physically fit as
possible. A person's power of resistance to an infectious disease
cannot be estimated from a weighing-up of his general physical
powers; neither physical nor mental powers are deciding factors
in the case. Any individual may be possessed of a feeble power of
resistance to one infectious disease and of a strong power
of resistance to another. Let me take as an example the
influenza epidemic of 1918-1919, which most of those present will
probably recollect. Now, what was the actual state of things
then? Why, it was just among the young, vigorous members of the
community that far larger numbers were cut off than was the case
among other groups. It would happen for instance that a vigorous,
full-blooded, muscular, intelligent, promising young man died of
the disease, whereas a feeble specimen, of poor intellect and of
no importance to the community, survived. That is how matters
stand actually. Moreover, it should not be forgotten either, that
those who pass through an infectious disease successfully have
nevertheless had their vitality injured by it to a greater or
less degree, have consequently forfeited some of their value as
members of the community. Hence, everything that medical science
can do to ward off and cure disease is of benefit to the
community, just from the point of view of its being contributory
to the health and vigour of the race. Circumstances are the same
respecting pernicious anaemia. The sufferers from the disease are
not of inferior value as human beings, except in the particular
respect in question. If their inferiority therein can be removed
by feeding them with liver, there is no reason why they should be
inferior in value in any other respect. Hence liver therapy not
only rescues persons suffering from pernicious anaemia from
death, it also restores them and renders them capable of living
useful and active lives to the benefit of the community.
If, now in conclusion, I sum up the discoveries for which the
prize has on this occasion been awarded, they are as follows: We
have acquired new knowledge as to the very divergent effects
exercised by different food substances in promoting and
stimulating the bone-marrow's activity in the regeneration of the
blood; we have been made acquainted with a new internal secretory
function possessed by the liver, that is of the utmost
importance; we have been furnished with a method of treatment for
pernicious anaemia, and also for other diseased conditions, that
will save the lives of many thousands of persons every year.
Hence it must be said that our prize-winners fulfil in an ideal
fashion Nobel's criteria for a prize-winner, since he lays it
down that the prize shall be bestowed on the person or persons
who have conferred the greatest benefit on mankind.
Now I turn to you, Professor Minot, Dr. Murphy, and Professor
Whipple. I have tried to give an idea of what you have done, of
the importance, of the greatness of what you have done. You have
spread a new light over the process of regeneration of the blood,
you have discovered a function of the liver, before you unknown
to science, you have invented and elaborated a new method for the
treatment of anaemia, especially pernicious anaemia, that
dreadful disease, which hitherto has killed practically everyone
who was afflicted by it. This new method, the liver treatment,
has saved already thousands of lives, and will in the future save
innumerable human beings from death.
The donator says in his will, that the prize should be given to
those, who have conferred the greatest benefit on humanity. The
Caroline Institute, in awarding you the Nobel Prize for
Physiology or Medicine, has acted then exactly along the line of
the intention of the donator. You belong to the very small number
of men, of whom can in truth be said, that they have done immense
services to mankind.
I ask you now to step down and receive from the hands of the King
of Sweden the prize of which you are so worthy.
From Nobel Lectures, Physiology or Medicine 1922-1941, Elsevier Publishing Company, Amsterdam, 1965
Copyright © The Nobel Foundation 1934
MLA style: "Physiology or Medicine 1934 - Presentation Speech". Nobelprize.org. 28 Aug 2010 http://nobelprize.org/nobel_prizes/medicine/laureates/1934/press.html