The Nobel prize in medicine for 1912 has just been awarded to Dr.
Alexis Carrel, a Frenchman, of Lyon, now employed at the Rockefeller
Institute of New York, for his entire work relating to the suture of
vessels and the transplantation of organs.
The remarkable results obtained in these fields by various
experimenters, of whom Carrel is most widely known, and also the
wonderful applications made of them by certain surgeons have already
been widely published.
The journals have frequently spoken lately of "cultures" of tissues
detached from the organism to which they belonged; and some of them,
exaggerating the results already obtained, have stated that it is now
possible to make living tissues grow and increase when so detached.
Having given these subjects much study I wish to state here what has
already been done and what we may hope to accomplish. As a matter of
fact we do not yet know how to construct living cells; the forms
obtained with mineral substances by Errera, Stephane Leduc, and others,
have only a remote resemblance to those of life; neither do we know how
to prevent death; but yet it is interesting to know that it is possible
to prolong for some time the life of organs, tissues, and cells after
they have been removed from the organism.
The idea of preserving the life of greater or lesser parts of an
organism occurred at about the same time to a number of persons, and
though the ends in view have been quite different, the investigations
have led to essentially similar results. The surgeons who for a long
time have transplanted various organs and grafted different tissues,
bits of skin among others, have sought to prolong the period during
which the grafts may be preserved alive from the time they are taken
from the parent individual until they are implanted either upon the
same subject or upon another. The physiologists have attempted to
isolate certain organs and preserve them alive for some time in order
to simplify their experiments by suppressing the complex action of the
nervous system and of glands which often render difficult a proper
interpretation of the experiments. The cytologists have tried to
preserve cells alive outside the organism in more simple and
well-defined conditions. These various efforts have already given, as
we shall see, very excellent results both as regards the theoretical
knowledge of vital phenomena and for the practise of surgery.
It has been possible to preserve for more or less time many organs in a
living condition when detached from the organism. The organ first tried
and which has been most frequently and completely investigated is the
heart. This is because of its resistance to any arrest of the
circulation and also because its survival is easily shown by its
contractility. In man the heart has been seen to beat spontaneously and
completely 25 minutes after a legal decapitation (Renard and Loye,
1887), and by massage of the organ its beating may be restored after it
has been arrested for 40 minutes (Rehn, 1909). By irrigation of the
heart and especially of its coronary vessels the period of revival may
be much prolonged.
The first experiments with artificial circulation in the isolated heart
were made in Ludwig's laboratory, but they were limited to the frog and
the inferior vertebrates. Since then experiments on the survival of the
heart have multiplied and become classic. Artificial circulation has
kept the heart of man contracting normally for 20 hours (Kuliabko,
1902), that of the monkey for 54 hours (Hering, 1903), that of the
rabbit for 5 days (Kuliabko, 1902), etc. It has also enabled us to
study the influence upon the heart of physical factors, such as
temperature, isotonia; chemical factors, such as various salts and the
different ions; and even complex pharmaceutical products. Kuliabko
(1902) was even able to note contractions in the heart of a rabbit that
had been kept in cold storage for 18 hours, and in the heart of a cat
similarly kept after 24 hours. The other muscular organs have naturally
been investigated in a manner analogous to that which has been used for
the heart; and for the same reason, because it can be readily seen
whether or not they are alive. The striated muscles survive for quite a
long time after removal, especially if they are preserved at the
temperature of the body and care is taken to prevent their drying. By
this method many investigations have been made of muscular contractions
in isolated muscles. Landois has noted that the muscles of a man may be
made to contract two hours and a half after removal, those of the frog
and the tortoise 10 days after. Recently Burrows (1911) has noted a
slight increase in the myotomes of the embryo chick after they have
been kept for 2 to 6 days in coagulated plasma.
Non-muscular organs may also survive a removal from the parent
organism, but the proofs of their survival are more difficult to
establish because of the absence of movements. Carrel (1906) grafted
fragments of vessels that had been in cold storage for several days
upon the course of a vessel of a living animal of the same species; in
1907 he grafted upon the abdominal aorta of a cat a segment of the
jugular vein of a dog removed 7 days previously, also a segment of the
carotid of a dog removed 20 days before; the circulation was
reestablished normally; these experiments have, however, been
criticized by Fleig, who thinks that the grafted fragments were dead
and served merely as supports and directors for the regeneration of the
vessels upon which they were set. In 1909 Carrel removed the left
kidney from a bitch, kept it out of the body for 50 minutes, and then
replaced it; the extirpation of the other kidney did not cause the
death of the animal, which remained for more than a year normal and in
good health, thus proving the success of the graft. In 1910 Carrel
succeeded with similar experiments on the spleen.
Taken altogether, these experiments show that the greater part, if not
all, of the bodily organs are able to survive for more or less time
after removal from the organism when favorable conditions are
furnished. There is no doubt but what the observed times of survival
may be considerably prolonged when we have a better knowledge of the
serums that are most favorable and the physical and chemical conditions
that are most advantageous.
If we can preserve the organs, we may expect to also keep alive the
tissues and cells of which they are composed. Biologists have studied
these problems, too, and have also obtained in this department some
very interesting results.
The cells which live naturally isolated in the organism, such as the
corpuscles of the blood and spermatozoa, were the first studied. Since
1910 experiments on the survival of tissues have multiplied and at the
same time more knowledge has been obtained concerning the conditions
most favorable to survival and the microscopical appearances of the
tissues so preserved. In 1910 Harrison, having placed fragments of an
embryo frog in a drop of coagulated lymph taken from an adult, saw them
continue their development for several weeks, the muscles and the
epithelium differentiating, the nervous rudiments sending out into the
lymph filaments similar to nerve fibers. Since 1910 with the aid of Dr.
Minot, I have succeeded in preserving alive the nerve cells of the
spinal ganglia of adult dogs and rabbits by placing them in
defibrinated blood of the same animal, through which there bubbled a
current of oxygen. At zero and perhaps better at 15°-20°, the structure
of the cells and their colorable substance is preserved without notable
change for at least four days; moreover, when the temperature is raised
again to 39°, certain of the cells give a proof of their survival by
forming new prolongations, often of a monstrous character. At 39° some
of the ganglion cells which have been preserved rapidly lose their
colorability and then their structure breaks up, but a certain number
of the others form numerous outgrowths extremely varied in appearance.
We have, besides, studied the influence of isotony, of agitation, and
of oxygenation, and these experiments have enabled me to ascertain the
best physical conditions required for the survival of nervous tissue.
In 1910, Burrows, employing the technique of Harrison, obtained results
similar to his with fragments of embryonic chickens. Since 1910 Carrel
and Burrows applied the same method to what they call the "culture" of
the tissues of the adult dog and rabbit; they have thus preserved and
even multiplied cells of cartilage, of the thyroid, the kidney, the
bone marrow, the spleen, of cancer, etc. Perhaps Carrel and his
collaborators may be criticized for calling "culture" that which is
merely a survival, but there still remains in their work a great
element of real interest.
Such are, too briefly summarized, the experiments which have been made
up to the present time. We can readily imagine the practical
consequences which we may very shortly hope to derive from them, and
the wonderful applications of them which will follow in the domain of
surgery. Without going so far as the dream of Dr. Moreau depicted by
Wells, since grafts do not succeed between animals of different
species, we may hope that soon, in many cases, the replacing of organs
will be no longer impossible, but even easy, thanks to methods of
conservation and survival which will enable us to have always at hand
material for exchange.
The dream of to-day may be reality to-morrow.
There are also other consequences which will follow from these
researches. I hope that they will permit us to study the physical and
chemical factors of life under much simpler conditions than heretofore,
and it is toward this end that I am directing my researches. They will
enable us to approach much nearer the solution of the old insoluble
problem of life and death. What indeed is the death of an organism all
of whose parts may yet survive for some time?
These, then, are the researches made in this domain, fecund from every
point of view, and the great increase in the number of experts who are
taking them up, while it is a proof of their interest, gives hope for
their rapid progress.