The human race - and all other mammals, too - has an acute case of inherited xenophobia; since it is a genetic characteristic, it is not a function of philosophical considerations, but of rough and rugged experience. Our very genes are afraid of strangers - fanatically and to the death. It's not logical, it's not rational - but it's very real and very practical.
Doctors call it "the immune reaction". The cells of our bodies reject all strangers, and attack any aliens that seek to find lodgment in our organism.
Over the course of the last few gigayears our evolutionary ancestors had to develop that reaction, and our more recent ancestors succeeded in living long enough to be ancestors only because they maintained that hair-trigger xenophobic reaction.
The community of cells called "an organism" must maintain trade with the external world and all its visible and invisible enemies and attackers. We have to eat, drink, and breathe - and all food, water and air is laden with constantly hungry would-be invaders.
The early students of microbic life had a hard time proving that life was not spontaneously generated, because until fully sterile procedures were worked out, their experimental setups were demonstrating - unrecognized by the experimenters! - the omnipresence of infective microbes.
Organisms had to evolve exceedingly sensitive, and subtle - "sophisticated" is the modern term as applied to technological gadgets - techniques for distinguishing friend (self) from foe (any other entity).
The system, even after gigayears of trial and error development, still doesn't function perfectly; there are many indications that several of the incurable disintegrative diseases represent failure of the organism's IFF (Identification Friend or Foe) system. Multiple sclerosis appears to be an instance of the IFF system becoming hypercritical, and misidentifying the organism's own nervous tissue as "foe".
On the other hand, there are indications that cancer results from a hypocritical IFF system failing to recognize the deadly, destructive mutated cells of cancer as "foe". While the change in the cells may be induced by a virus, a chemical, or hard radiation, the cancer itself is not a virus, chemical, or radiation - it's a mass of body-cells-gone-wrong. Cells that no longer have the normal cell's self-limiting characteristics, the self-discipline that causes it to stop endless reproduction when the organ of which it is a part is fully developed.
It's probable that we all have some cancer cells - just as we all have many disease-causing microbes in our bodies. But the normal individual's IFF system quickly spots the malign, mutated cells, designates them "foe", and destroys them - just as his IFF system also spots the disease-causers and attacks them.
That inherited xenophobia is absolutely essential to living in a normal planetary ecology. It's even sophisticated enough to recognize allies - nonhuman allies - and permit them to exist in the organism. Provided they stay in their proper place, that is! The various symbiotic bacteria that live in our digestive tract supply us - in return for food and protection - with various vitamins that we ourselves cannot produce. Cholera bacilli, on the other hand, are attacked vigorously if they show up in the intestines. But the normal colon bacilli, if they stray out of the intestines, are immediately labeled "Foe!" and attacked vigorously. Frequently the result shows up as painful boils, or worse. The colon bacilli are "all right in their place, but..."
In other words, that IFF system Man's evolutionary ancestors developed (1) had to be developed, and (2) had to be passed on genetically, and (3) had to be exceedingly sensitive, complex, and fast-acting. The problem that IFF system faces is extremely subtle; the would-be invaders have evolved right along with us, and have sought to develop camouflage techniques good enough to sneak past the defenses. Some disease-causers have been very dangerously successful at camouflage - the TB germ, for instance, can find lodgment, and remain living happily in a man's lungs for years, because the body's immune reactions aren't triggered into violent counterattack.
At the same time, the IFF system must be able to recognize such enormously different cells as the dense, calcium phosphate loaded bone cells, the physically practically strengthless nerve cells, the muscle, tendon, and connective tissue cells, and the chemical-manufacturing-plant cells of liver, thyroid, pancreas, adrenals, pituitary and all the thousands of variants and special function cells as being "friend".
It must work - or you die. You must have that functioning IFF system, and the functioning enforcing agency of leucocytes and antibodies, or you die quickly.
It has to be highly specific; it must not attack any of the million and one varieties of the organism's own specialized cells, and yet it must attack any invader, any alien - except symbiotes operating in their proper place.
Anybody want to try starting from scratch and working out something that would do that?
Any nation's Security Forces would certainly love to see a system that would faultlessly and immediately identify all loyal citizens, and yet spot every would-be infiltrator and/or home-grown deviant crackpot.
The job of organism Security rests on the Immune Reaction system - combined Internal Security, Detective Bureau, Counterespionage, Police Force and Military. And just as the Army Engineers are responsible not only for fighting external enemies, but also for many internal engineering problems, so the Immune Reaction also has the job of cleaning up after such "natural disasters" as a deep-driven splinter that has to be removed, after the alien invaders who rode it into the flesh have been disposed of. After the infection has been subdued, the mechanical mass of wood has to be cleared away somehow.

It took a good bit of work and experimenting for surgeons to discover materials that the body would tolerate in making surgical repairs - special alloys of tantalum, stainless steels, and silver. More recently, various extremely inert plastics have been found useful - partly because their chemical nature is such they defy any biochemical attack, and partly because they're so inert they don't react against and excite the immune reaction.
When surgeons started trying to replace lost parts of the human body - and they've been trying through all of human history! - they didn't, of course, know about the immune reaction. But they repeatedly learned that something was there that made it impossible.
The first successes in replacements came with blood transfusions, and the cornea of the eye. Blood transfusions were tried first, of course, with animal blood - usually a lamb's, because everybody knows that lambs are very pure animals.
Since that quite consistently killed the recipient almost as quickly as it did the small donor - the lamb's blood naturally had its own immune reaction, and started fighting the recipient's alien cells, with mutually lethal results - that was dropped.
Transfusions of human blood into human patients had a bewildering inconsistency; sometimes it worked magnificently, and a man surely dying would, in a matter of minutes, bounce back to strength and make a rapid, complete recovery. And usually the patient died very shortly.
The early efforts, of course, ran into two difficulties - the obvious-to-us one of blood-type incompatibility, and the not-so-obvious one that you can't take blood from one man's arm, run it through a rubber tube or the like, directly into another man's veins and expect it to be, and remain, free of clots. Blood is very specially designed to clot and plug up leaks in the circulatory system; the trigger of that clotting reaction is contact with something other than the special lining of blood vessels. Rubber tubes aren't lined with blood-vessel tissue. In the early days they sometimes got away with it by making a direct blood-vessel-to-blood-vessel transfusion - more by good luck than technical validity.
When blood-typing was discovered, the success of blood transfusions rose to a practicable level; instead of being a desperate last-chance, what-have-we-got-to-lose measure, it became a therapeutic technique. The discovery of the simple anticlotting techniques involving sodium citrate vastly improved matters.
The reason those two "organ transplants" - corneas and blood - worked was simply because (1) the cornea has no blood circulation, and the immune reaction isn't triggered by reason of no contact, and (2) blood is a temporary thing anyway. A skin graft fails because it is sloughed off in a matter of a few weeks; blood has a service life of only a few weeks anyway. The transfused blood is rapidly destroyed, too - but not before it's served its temporary purpose. It's rather like the suture materials a surgeon uses in suturing internal tissues; they're made of chemically treated animal tissues which are attacked by the body and dissolved away in a matter of a couple of weeks - by which time they've served the intended purpose of holding the wound closed until healing has knit the tissues again.
As the immune reaction became better recognized, efforts at organ transplants were largely abandoned; about the only consistent efforts were in the direction of skin grafts. Man-to-man skin grafts never "take" except in the case of genetically identical twins - it is, in fact, the current best proof of "one-egg" twinship. Fraternal twins may look alike - but skin grafts won't "take".
If you don't have an identical twin, and must have a skin graft - the surgeon will take skin from one part of your body and graft it where needed.
This recognition of homografting as a successful technique led to bone grafts, on the same basis; a piece of a bone from one part of a patient's body could be sawed out and installed in another place to act as a bridge, so that sound bone could grow around it and unite separated damaged bone-ends.
That technique worked, and many a patient had function restored after what would have been a permanently crippling injury. Homografts worked.

Grafts from identical twins worked. Even complex organs such as kidneys could be grafted between identical twins.
But that genetic xenophobia blocked efforts between nonidentical-twin individuals. To optimize the chances of success, the blood types of the two individuals had to be matched, for the biochemistry of the blood is naturally matched to the other cells of the organism.
As the immune reaction became understood, and surgeons found it blocking their efforts, their natural response was to seek ways and means of suppressing that xenophobia. If only that damned xenophobia didn't act up, this man, dying because of diseased kidneys, could be given this perfectly healthy and functional kidney from this other individual who has just been killed in an accident. But make the transplant - and the stupid immune reaction kills the transplanted organ that could save the whole organism, if it were only given a chance.
They found ways to suppress the immune reaction - with predictable results. With no immune reaction, the body's defenses against disease collapsed. Antibiotics are wonder drugs - but they aren't that wonderful! There are a lot of germs that antibiotics don't bother much. So far as I know, none of the suppressed-immune-reaction patients has lived long enough to have time to develop cancer, but that would probably show up; the Internal Security system wouldn't be able to react against traitors, deviants and crackpot cells.
Inasmuch as the immune-suppression techniques involve heavy doses of carcinogenic drugs and radiations, even a perfectly normal, healthy person subjected to that therapy could reasonably be expected to develop cancer.
But as I say, I know of no case where survival has been extended enough for that reaction to appear.

It seems to me that the approach now being attempted is, at the very best, a blowout-patch, temporary expedient type of thing.
It works just fine for blood transfusions - because blood's inherently temporary.
It will never work for more complex, normally permanent organs - because that immune reaction, that ancient IFF system, must be retained to defend the organism against the would-be invaders that are constantly menacing us.
The first successful human heart transplant - a magnificent achievement of surgical technique - was performed by a South African surgical team; a dying girl's heart was transplanted into the chest of a man dying of heart disease. The girl was dead before the operation was begun, of course - but she died in the hospital after an automobile accident, solely due to mechanical injury, not to any breakdown of health. And the team of surgeons was able to know sufficiently before her death that she would die - with a crushed skull there was no chance of life - and make the necessary elaborate preparations.
The man was dying anyway - it was a matter of days at most for him: the gamble was worth it.
And the operation was completely successful - a true triumph of exquisite surgical technique and skill.
The result can be predicted as death; at this writing Mr. Louis Washkansky hasn't yet died, but the result will be death.
Initially, the tissues were not well matched; the girl's blood type was 0, the "universal donor" type. She could have given Mr. Washkansky a blood transfusion, because the 0-type blood does not carry antibodies that attack either type A, B, or AB. But a blood transfusion is a temporary thing anyway; a heart transplant is intended to be permanent. The Type 0 heart tissues were not a match for anything but a Type 0 recipient - and Mr. Washkansky was not.
Second, the IFF mechanism obviously has to work on the basis of genetic coding of the cells. The only thing that is "the same" about all the cells in any individual's body is that they all carry exactly the same genetic code - whether they specialized as nerve cells, kidney cells, heart muscle or pituitary cells, they all stemmed from the same original fertile ovum cell. Genetically they are identical - which is why grafts between one-egg twins are as successful as homografts. The Security Force reacts against any cell that does not carry the genetic code of native-born citizens in good standing - and only descendants of that original fertile ovum, of all the entities in the Universe, carry that precise genetic coding.
The tissues of the heart donor were markedly different; she was a young woman, and, therefore, had, in every cell, one more chromosome than did the cells of the man.
The immune-reaction suppression drugs and radiation did suppress immediate rejection reactions, and the transplanted heart functioned well in its new environment; healing of the wound proceeded normally.
But actually, the immune reaction cannot be completely suppressed, even temporarily. That genetic xenophobia is far too deep in the cells; it's been in our genes not for mere millions of years - it's been there for at least a billion years. And it's been absolutely essential to survival through all billion years. It's not something that's going to be tossed overboard lightly or easily.
The "suppression" seems, rather, to be a disturbance, a distortion, of the mechanism. Like a man who's been knocked on the head heavily, it's dazed and confused.
Mr. Washkansky's confused IFF system seems to have made a serious mistake in that dazed condition; when the immune reaction system recovered enough to act - it "recognized" his own lung tissue as "foe" apparently.
The effort at organ transplantation by any means is valid - when there is nothing else possible. The South African team proceeded correctly; both patients had nothing whatever to lose, and there was a chance of very great gain in knowledge.
But the approach to transplantation by suppression of that crucially important immune reaction is invalid - save only as a measure of recognized desperation, recognized as, at the very best, a short-term expedient. Interfere with the IFF system only at your dire peril; upset it and it may react against your own tissues, or simply fail to react against any invading germ. In either case, your normal, healthy life is ended; in one case your own tissues destroy themselves; in the other, you can live only in a sterile, germ-free, totally-sealed environment. Antibiotics can't replace your natural antibody defenses.

The approach to true organ transplantation is, it seems to me, to accept the nature of that genetic xenophobia, and comply with it. Homografts succeed brilliantly. Use that approach.
True - while a man has skin to move from one spot to another, and bone can be shifted around, and the wounds heal - who's got a spare heart to move into place? Unless you had an identical twin who happened to get killed in an accident that didn't injure his heart, where can you get a homograft heart?
I think the answer is "Grow one!" Grow a spare heart, kidney, liver - whatever it is that's needed.
That's not impossible; organs can be kept alive in vitro; it's been found that kidney or liver cells, chopped up bits of kidney, stirred in nutrient solution, will cluster and reorganize themselves in a definite effort to reconstruct an organ.
This field is almost unexplored - yet half a century ago Alexis Carrel showed that a bit of chicken heart could be kept alive and grew rapidly as long as anyone wanted to supply the fresh nutrient medium.
Biopsy techniques have been developed which permit samples of the tissues of almost any organ to be abstracted. Cultured to grow a new complete organ, that substitute would have the identical genetic code of the individual from whom the cells were taken. They would, therefore, constitute a homograft - and there would be no immune reaction to contend with.
True; there's a long road of research and development to be traversed down that path. But that path conforms with the gigayear-old demands of the immensely important survival characteristic - genetic xenophobia. It fits a very deep and ancient law of nature.
The present bulldozer approach, seeking to suppress that law of nature, is inherently contra-scientific. True science docs not seek to override, or discard, laws of nature - it seeks to understand and apply them.
To grow a new organ will take time, of course, just how long we cannot really guesstimate at this juncture. What can be done, then, for a man who suddenly has to have a replacement for an inoperative heart - and can't wait a few weeks to culture a new one?
I suspect the external mechanical heart will be a better solution; we already know that the body can tolerate - and for extensive periods - metal and plastic structural materials, without upsetting the IFF system. The fact that such a mechanical contraption is unsatisfactory by reason of clumsiness, and dependence on a technological power supply does not inhibit its use as a stopgap measure while a new homograft organ is being grown.
Normally, kidney failures give months of notice; there would be adequate time for new organ growth; if special circumstances require immediate help, the clumsy, but workable artificial kidney devices are already available. Livers, spleens, a dozen different organs could be replaced successfully as homografts.
And with no need to disturb the intricate, highly sophisticated, and enormously effective immune reaction, it would no longer be a case of "by a feat of brilliant surgical technique, the operation was successful... but the patient died".
It's long been suggested that, if organ-transplant techniques were successfully developed, some really sticky ethical problems would start popping up. Ruthless, powerful, dying men would not be content to wait in hope that someone with the right blood and tissue type would happen to be killed in an accident that didn't injure the needed new organ. Accidents can be produced to order.
But so long as the ancient genetic xenophobia operates - even if that heterograft organ were ruthlessly arranged for - it could mean only a short span of miserable, defenseless semi-life.
The homograft approach will take a lot of research that hasn't yet been started - but that road is clear of legal, ethical, and moral blocks. It's also scientifically sound - because it doesn't seek to override, to suppress, a law of nature.
It just requires a full, hard developmental effort along the line of organ culture. A developmental approach that respects and works with, not against, a law of nature- which is the essence of sound science.

April 1968

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