DISCOVERY OF EXTRACT THAT HAS POWER
TO RESTORE CAPACITY LOST IN DIABETES
IS WADE PUBLIC BY DR. JOHN R MURLIN
IS REVOLUTIONARY
Discovery Means Disease
Long Incurable Now
Can Be Combated.
STEPS TO BE TAKEN
Best Method of Applying
Extract to Cases Is to
Be Worked Out.
A discovery that is believed to
pave the way to a cure of diabetes
and so remove one of the major
causes of death was announced at
a meeting of the Rochester Medi-
cal Association last night by Dr.
John R. Murlin, director of the
department of vital economics at
the University of Rochester.
The discovery, revolutionary in
its effect upon disease, was de-
scribed in the following words of
Dr. Murlin at the close of his ad-
dress.
"... we claim the credit for
having proved first that pancreat-
ic extract can restore the lost
power to oxidize sugar to animals .
rendered diabetic by removal of
pancreas. This we have con-
firmed many times the past sum-
mer and this we maintain is the
crux of the whole problem. The
best- method of preparation for
administration to human cases
probably has not yet been accom-
plished. We must find a way to
give it by mouth, as thyroid ex-
tract is gen, and then the ter
rors of diabetes will have disap-
peared. One of the major causes
of death will have been complete-
ly removed."
Dr. Murlin acknowledges the
work done in Rochester with him
in working out the problem by
Dr. Harry D. Clough, Dr. Arthur
M. Stokes, Dr. C. B. F. Givvs
and Dr. Clyde C. Sutter.
Diabetes Long Incurable.
The importance of the discov-
ery made by Dr. Murlin and his
associates is described in- the first
issue of the, Rochester Alumni
which makes its appear-
ancee to-day, in part as
follows:
The very great importance of this work
to humanity can be realized when one
recalls the public furore created a few
years ago by the premature announcement
of an alleged cure for tuberculosis.
For generations past diabetes had taken
its place alongside tuberculosis and
Bright's disease as one of the seemingly
incurable secourges which has baffled
every attack of meical science. Now
it is fast losing its hopeless status,
and Dr. Murlin's announcement is
neither premature, nor must his result be
cursed by the qualifying word, "alleged."
Location Long Established.
The general nature of diabetes is too
well known to require
elaboration. It was established as
far back as 1889 that the
pancreas is the seat of the disease.
Certain cells in this organ
produce what has been labeled
Glucopyron, meaning a sugar burning
substance. When these cells
fail to function, the sugar in the
system is not longer burned, but
is excreted through the kidneys,
and diabetes exists. The problem,
then was to furnish a substance
for the work of those pancreatic
cells, which could be accomplished
by introducing into the system an
extract made from healthy cells.
Dr. Murlin began working on the
developments of this
idea in 1912, while assistant
professor of physiology in Cornell
medical college. Associated with
him in carrying out the experiments
was his assistant professor of
pediatrics, at Johns Hopkins
University. With the exception
of one encouraging experiment
on a human case in 1912, all
their early work was done with animals.
By 1916 they were able to
publish satisfactory results, showing
that a dog, with pancreas entirely
removed, could burn sugar when
given an extract from its own
pancreas. Shortly after that Dr.
Kramer left Cornell. Then the war
took Dr. Murlin into the service.
After he had received the
appointment as head of Rochesters
new department, as soon as possible
after coming here in 1919
and getting his laboratory
organized, he set out on a two-year
program, with confidence that he
could conquer the diabetes
problem within that period. Now,
entirely unknown to Dr. Murlin,
one of these odd coincidences
which are frequently cropping
out in the world of research was
taking place. DR. F. G. Banting
had been inspired by much the
same idea and was working along
very similar lines in the
laboratory of Dr. J. J. R. MacLeod,
professor of physiology at the
University of Toronto.
Dr. Murlin did not receive any
intimation of Dr. Bantings
work until last December, and
he did not see any report on its
results until April of this year.
This served to speed up his
own endeavor; another laboratory
assistant was added to his
staff, and a program of very
intensive work laid out for the
summer months. As a result,
they were able to give the first
injection of the new extract
to a human patient early in July
and have been treating cases
with more or less regularity and
gratifying results ever since.
Two Doctors Now Concer.
Associated with Dr. Murlin in
his work at Rochester have been
Dr. Arthur M. Stokes, a Rochester
graduate of the class of 1913,
who also studied under Dr. Murlin
at Cornell, Dr. Harry G.
Clough, Dr. C. B. F. Gibbs and
Neil C. Stone, class of 1919
at Rochester, now in the Cornell
medical college. They are
working on specific cases
with local doctors, including
Complete Text of Dr. Murlin's Address Outlining
Steps Leading to Epoch-making Medical Discovery
It is now thirty years since Minkowski and
V. Mehring made the discovery that the seat
of the disease diabetes mellitus is in the
pancreas. This thirtieth year has been
signalized by another discovery which
may prove to have been just as important
as that of Minkowski and V. Mehring
I refer of course to experiments of
Drs. Banting and Best at the
University of Toronto. The former
discovery was based upon the complete
removal of the pancreas from dogs,
producing a fatal condition alike in
all essential respects to the disease
in man. Banting and Bests observations
were based upon ligation of the pancreatic
ducts producing degeneration of the
acinous tissue in the pancreas thus
making it possible to secure by extraction
the active anti-diabetic substance
produced by the Islet cells in a state
of purity never previously attained.
It is a mistake to suppose the
pancreatic extracts had not been
prepared before or to suppose that
they had not been used with some
success on human cases. It is, no
discredit to Banting and Best, rather
the contrary, to say that more than
twenty scientific experimenters had
made extracts which diminished the
excretion of human cases of severe
diabetes before they had done so.
In several instance these preparations
caused the complete disappearance of
sugar from the urine, caused increase
in weight, and general improvement
But most of these attempts had to be
abandoned because of toxic or other
deleterious results which over shadowed
the benefits gained. Previous
Research Sketch. Let me review
briefly the history of these researches.
Minkowski himself, the next year after
his original discovery with V. Mehring
in 1892, tried to make an extract of
dogs pancreas which when injected into
the animal from which it had been taken
would restore his power to metabolize
sugar. He failed completely.
Even before Minkowski, but stimulated
by his discovery, Caparelli made an
extract of dogs pancreas in 0.75%
NaCl which, when injected into the
peritoneal cavity of a dog caused an
abrupt fall in the excretion of sugar
within three hours and inmost instances
complete disappearance soon thereafter.
In 1893 also clinical trails of pancreatic
material were made by Ballistini in Italy
and by Ralfe, Sibley, Wood, Mackenzie, and
White in England. Ballistini, Sibley and
Ralfe reported some success; the other
reported failures. Some of them gave
fresh pancreas or pancreas slightly cooked
by mouth, some gave press were positive
reports by Ausset in France and Bormann
in Russia, negative results by Vanni and
Burzagli in Italy. The first, Ausset
used raw pancreas of veal upon a
depancratized dog and a single human case.
Bormann used roast pancreas by mouth,
later rectal infusions and finally
sub-cutaneous injections. One of his
patients who received 1 1-2 cc. Of pancreatic
extract daily under the skin gained eight pounds
in six weeks, the diet remaining substantially
the same. Vanni and Burzagli used a glycerine
extract and also raw pancreatic extract
given subcutaneously. There was
no clearly favorable result. Both
Sides Defended. In 1896 there was
one report upon each side of the
controversy. Lisser reported from
Odessa that rectal infusions made
from hashed fresh pancreas with
normal saline caused marked diminution
both of the glycosuria and polyuria.
One case gained two and one-half kgm.
In weight, the other four kgm, but
in the latter case the infusions
could not be tolerated longer.
Spillmann reported two cases treated
by injection with pancreatic press
juice. There was only slight
abatement of the glycosureia.
In 1897 Thesen and Lauritzen found
favorable effects in human cases,
the former feeding 50 to 300 gms. Of
raw pancreas daily, the latter a
glycerine extract given by mouth.
Thesen found, as many other have
found since, that raw pancreas soon
becomes repugnant. This year also a
notable piece of work was done by
Hogounenq and Doyon upon depancratized
dogs They made extract in a great
variety of ways, but were not able
to demonstrate any beneficial effects
when thy were administered to
depancratized dogs by stomach.
This well-controlled work made a
marked impression on clinicians
and very considerably discouraged
the pancreatic material in any
form by mouth; particularly as it
was followed the next year by the
observations of Hedon to the effect
that glycerine extract given by mouth
to depancratized dogs produced almost
no effect. Blumenthal however saved
the record for 1898 by squeezing out
the juice from raw pancreas in much
the same way, though not employing
such high pressures, as Buchner
used in obtaining zymase from yeast
He precipitate the proteins from
his juice with alcohol and gave
the filtrate to animals as well as
to human cases. Given intravenously
it killed his animals, but caused
only necrosis at the site of
injection when given subcutaneously
either to animals or men with
fatal diabetes. In one case he
report 40 per cent increase in
the combustion (meaning utilization )
of sugar. It is obvious why he
discontinue its use. Nevertheless
Blumenthal was on the right track.
Significant Step in 1898. Another
significant observation this year
(1898) was that of Lepine and
Martz who examined the lymph of
a normal dog and found a substance
capable, when injected intravenously
into a rabbit of causing a marked
glycolysis i.e. disappearance of
sugar from its blood. No further
advance in the therapeutic use of
pancreatic material was made for
ten years. Lepine is the only
outstanding worker who seemed
never to lose faith in the
ultimate solution along the lines
of his glycolytic ferment. He
believed that the pancreas produced
such a ferment and gave it off
mainly to the lymph rather than
the blood; that this ferment was
sinaqua non for the breakdown of
sugar, the absence or failure of
which produced diabetes.
Meantime observations were made
identifying the Islands of Langerhans
as that part of the pancreas
responsible for the failure in
diabetes. The principal workers
engaged in this pathological work
have been Gutman, Lepine, La Guesse,
Karakascheff, Adelheim, Fraenkel,
and in this country Opie, MacCallum
and Cecil. Research is Extended.
This period from 1898 to 1908 was
marked also by the development of
the dietary treatment of diabetes
and by the inauguration of almost
endless researches upon the metabolism
of diabetes which have by no means
exhausted the subject even yet.
The salient points for our present
purpose established by these
investigations are the following:
(1) The primary defect in diabetes
is not the excessive production of
sugar but the inability of the
organism to oxidize it. (2) This
condition is signalized ordinarily
by the attainment of a certain ratio
(3.65) of glucose being in excess of
glucose ingested; also by the attainment
of a reparatory quotient of .069.
(3) To attain these numerical levels
the diabetes excretes all the sugar
which is formed in the course of the
metabolism of protein as well as all
his carbohydrate and this amounts to
as much as 60 per cent. Of its
weight. (4) There is an excessive
heat production in diabetes which
is caused by the increased metabolism
of protein. (5) The acidosis of
diabetes arises from the inability
of the diabetic to complete the
oxidation of fatty acids and certain
amino acids, with the result that these
acids are excreted (acidura) but
especially also they delete the