CHAPTER 20

Transplants

The Marvels Wrought by Plastic Surgery

Immured within the walls of the Rockefeller Institute for Medical Research as in a fortress, inaccessible and assailed in vain by the most bitter of the anti-vivisectionists, Dr. Alexis Carrel is carrying on wonderful experimental work in plastic surgery, which, in the view of many of the foremost men in the medical world to-day, is destined to entitle him to rank forever with the great pioneers of medicine and surgery.

Shrinking from publicity and appearing only at rare intervals before some ultra-scientific body to tell of the successful transplantation of organs and tissues from a dead or living animal to another living animal, the world hears but little of him and his work. Distinguished surgeons, admitting their inability to do the things that Dr. Carrel does with ease, speak of his achievements as marvelous.

Lest it be thought that Dr. Carrel’s theories and experimental work have as yet no practical application in regard to the conservation of human life, let us consider the following case:

On March 4 last a daughter was born to a well-known surgeon of this city and his wife. The child weighed 8 pounds and 12 ounces at birth and appeared to be strong and healthy. In a few hours, however, it developed melaena neonatorum, which signifies “hemorrhage of the new born,” a disease of the first two weeks of life and whose prognosis is extremely grave, the mortality ranging from 50 to 80 per cent. The child bled from the mouth, nose and intestines, and vomited blood. On March 8 the baby was near death.

In this extremity the surgeon-father invoked the aid of Dr. Carrel, with whose skill and theories he was familiar. Dr. Carrel, assisted by Dr. George E. Brewer, Surgeon to Roosevelt Hospital, proceeded as follows.

Case of Blood Transfusion

The right leg of the child was held firmly and an incision was made in the hollow back of the knee, exposing a large vein which was severed. An incision was then made in the left wrist of the child’s father and the radial artery, or pulse, exposed. This artery likewise was cut, and Dr. Carrel, whose technique in this line of work is described as amazing by his confreres, then proceeded to sew an end of the father’s severed artery to an end of the child’s severed vein.

Here was direct transfusion of blood. For some time the father’s blood was allowed to flow into the anaemic and impoverished system of the child. In a few moments the baby’s skin took on a healthy glow. As if by magic the vomiting and hemorrhage ceased, not to recur. In a word, the child was dying one minute, the next minute was a strong, healthy child. To-day this child weighs 6 pounds more than another born within a few days of it.

Dr. S. W. Lambert, commenting upon the foregoing case, said:

“The striking thing in the case is that the disease ceased suddenly and the child was cured from the moment of the transfusion of blood.”

One of the most distinguished surgeons in America declared that this daring procedure demonstrated the fact that whereas, if the child had died, it would have been believed that the hemorrhages were the result of deficiencies in the walls of the blood vessels, yet the method of curing the baby proved absolutely that the disease was due to some deficiency in the blood itself. The healthy blood of the father, he declared, had brought about the required chemical change in the child’s blood. He added that Dr. Carrel’s method of direct transfusion was a distinct improvement over the old method of using a glass tune as an intermediary. The old method he characterized as dangerous, explaining that a clot might be formed in the tube and that this might be carried through the patient’s lungs and to the heart, causing instant death.

But what of the transplantation of organs in the human being? The substitution of a healthy kidney for a diseased one? Are these miracles about to be accomplished? Dr. Carrel says so, and points out that he is accomplishing such things almost daily in his laboratory in the Rockefeller Institute in the cases of lower animals.

Some Possibilities Expected

The possibility of such physical regenerations in man is predicted by Dr. Simon Flexner, Director of the Rockefeller Institute. He does not promise that it will be possible right away to give a man a new heart or stomach or kidneys in place of the ones that may be ready to fail him, but be holds out hope that some day medical science will be able to do that very thing. He declares that these substitutions will be made possible through the new experimental surgery and vivisection, and will revolutionize modern medicine.

The successful transplanting of arteries from one animal to another, he says, was the first step toward this end.

“The technical surgical operations involved in this kind of experimentation, on account of the necessity of maintaining unimpaired the circulation of the blood, are great,” says Dr. Flexner, “but no effort should be spared to reach this goal.”

“It is a matter of no small significance that arteries can be transplanted successfully from dog to cat, and vice versa, and from man to dog, and that keeping extirpated arteries under sterile conditions at refrigerator temperature for twenty or thirty days, or even longer, does not interfere with the results of transplantation.”

Dr. Carrel is a native of France. He is a young man, still in the thirties, and was graduated from the University of Lyons. Immediately after graduation he took up original research work involving laboratory experimentation similar to that he is now engaged in. After spending a considerable period in Lyons he was induced to continue his researches in the laboratories of McGill University in Montreal. Then he was sought out by the University of Chicago, and he carried on his work there for two years. By this time his work as an original investigator had become widely known in scientific circles, and two years ago Dr. Flexner induced him to pursue his researches in the Rockefeller Institute.

The latest of Dr. Carrel’s rare semi-public appearances was made before the American Philosophical Society in Philadelphia, of which Dr. W. W. Keen, the distinguished surgeon, is President. This society, founded by Benjamin Franklin, who was also its first President, in 1743, has the distinction of being the oldest scientific society in America. Thomas Jefferson was its second President. The transactions of this society reach similar organizations all over the world, and it was to disseminate more generally a knowledge of Dr. Carrel’s work that he was urged to appear before it. He gave an illustrated lecture, showing some of the remarkable things he has accomplished. It is notable, however, that the word vivisection was not mentioned by Dr. Carrel at the meeting.

One experiment described by him indicates in itself the tremendous significance of his work and foreshadows its value in the relief of human suffering when the methods of procedure shall have been perfected. Following is an experiment which Dr. Carrel described as a “simple transplantation”:

Having anaesthetized a cat so that the subsequent operation was absolutely painless, Dr. Carrel removed the kidneys, together with their blood vessels, the aorta (the largest artery in the body), the vena cava (the largest vein in the body), the nerves, the nervous ganglia (or centres), the urethers (the tubes running from the kidneys to the bladder), and part of the bladder. These organs were replaced by similar organs from another cat. The cat with the new organs recovered and the organs resumed their functions.

“No therapeutic value can be expected from a graft of kidneys,” said Dr. Carrel, in commenting on this particular experiment, “unless the secretions of the new organs should be practically normal.” Dr. Carrel performed somewhat similar experiments, though not on as extensive a scale as the foregoing, on dogs at the University of Lyons as early as 1902, and again in Chicago in 1905. The first transplantation in mass was made by Dr. Carrel, assisted by Dr. Guthrie, at the University of Chicago, in 1906. He modified and improved his methods of procedure in the Rockefeller Institute last year.

“All resources of modern surgery must be used,” said Dr. Carrel, “to prevent infection and shock after such an operation.”

Up to Jan. 1, 1908, Dr. Carrel said he had effected fourteen such transplantations in mass. Five of the animals died and nine recovered, a most encouraging ratio. In all nine cases the functions of the kidneys were re-established.

These and many other experiments were described by Dr. Carrel in his Philadelphia lecture. He told how the leg of one dog had been grafted on another dog, and of how the glands of an animal were kept in cold storage for sixty days and then successfully transplanted.

At the conclusion of the lecture Dr. Keen said:

“While it may seem rather a dream, it is quite possible from what we have heard to-night that the time may come when it will be possible for a human being who is possessed of defective kidneys, for instance, to go to some hospital and have a fresh, healthy set taken out of the refrigerator for his benefit.”

Dr. Carrel was asked if such a thing could be done.

“Most assuredly it could be done,” he replied. “I could do it now, and it would be an easier operation to perform on a man than on a dog or cat. The great trouble is, who is going to supply the fresh, healthy kidneys?”

Transplanting Arteries

Dr. Carrel explained that in these transplantation operations—for instance, in the case of arteries—the first thing for the surgeon to accomplish was the immediate establishment of blood circulation. In this act the tissue must needs be kept alive outside of the body of the animal. The skill and technique of the work lay in the suture or sewing together of the two parts.

Dr. Carrel showed enlarged photographs of arteries which had been joined and through which blood had been coursing for months, which showed to the lay eye no sign of even a scar, only an experienced surgeon being able to distinguish the exact spot of the jointure.

The animals subjected to these experiments, Dr. Carrel said, were etherized in a room which had been thoroughly sterilized. The physicians were encased in sterilized masks and coverings, as the slightest infection would ruin the experiments. The animals suffered no pain and received as good, if not better, care than human beings would in the best equipped hospitals. He proved this by showing photographs of animals before and in the course of operations, compared with photographs of the same animals months and years afterward, in which they were seen to be jumping and skipping about in apparently complete health.

“Some time ago,” Dr. Carrel said, “I received a human leg from a New York hospital. I removed some of the arteries and put them in a dog, which easily survived the operation and remained healthy. I opened the dog later and found that it was doing beautifully. The important thing is whether the tissue from animals can be used in man.”

It was explained after the lecture that this had been done in minor ways.

Dr. Carrel showed pictures on the screen of the operation of grafting the leg of a dog which had just died on the stump of a leg of a fox terrier. The bones knit and the tissues healed and grew and remained healthy. Kidneys, glands, and veins were shifted between animals with success.

In response to the attacks of the anti-vivisectionists, Dr. Flexner already has answered them through The Times. He said:

“The people who oppose the use of animals in scientific research may be sincere enough—I do not doubt that. But they are ignorant, misguided, or misinformed. Their efforts are based, as often as not, purely on sentiment.

“To pass a law restricting or preventing vivisection on such a basis would be a grave injustice. Let these people inform themselves of the facts. Let them know what the use of these animals means to medicine and to mankind. Then let the law be offered only after full investigation.

“Birds and animals are being constantly put to death to supply mankind with adornments or for no reason at all. Birds are killed that their feathers may be used for women’s hats—killed in the mating season, for only when birds are mating is their plumage at its best. Animals are killed for their furs. They are caught in traps and thereby subjected to pain greater than that of any animal used for science, for their pain lasts for many days.

“The animals used for medical science suffer, but no more than a human being suffers under an operation. Men and women permit operations upon themselves to save life and relieve pain. Yet those who oppose vivisection would not have science operate on animals to cure men of their ills.”

Yet, while the opponents of vivisection scoff the majority of them are unaware that through the agency of animal experimentation there are men and women going about their daily tasks in the full enjoyment of health, using the healthy bones, joints, and tissues taken from others in place of their own diseased and useless joints and necrosed bones. Such, however, is the case. These substitutions have been made with the most gratifying results along lines and in accordance with theories similar to those entertained by Dr. Carrel.

Operating on Bones and Joints

Prof. Erich Lexer, Director of the Royal Surgical University Clinic and Polyclinic of Königsberg, Prussia, has described some remarkable operations on bones and joints, and his description has been translated for Surgery, Gynecology, and Obstetrics by Dr. E. C. Riebel of Chicago.

After reviewing the history of attempts to restore motion to joints stiffened by bony anchylosis, Dr. Lexer says:

“Bony anchylosis can be removed by operation only.”

Dr. Lexer had intended, he says, when he operated for a stiff joint again, to cover the surfaces of the joints with plates of joint cartilage from amputated extremities. In the meantime an article by Weglowski appeared which showed that the plan could be successfully carried out. Weglowski implanted cartilage between the bony surfaces of a stiff elbow joint after removal of superfluous bone and fashioning the ends so that they approximated the contour of a normal healthy joint. He took two pieces of cartilage from the sixth and seventh ribs and laid them side by side in the newly formed joint.

Unfortunately this patient died of pneumonia at the expiration of five weeks. It was possible then, however, to show that the transplantation had been successful. One side of the cartilages had grown firmly to the end of the upper arm bone.

“At the margins the cartilage decreased, to merge, without distinct boundaries with the surface of the bone. This proved the advantage of cartilage interposition: the transplanted pieces grew not only to the one bone surface, but flattened out and covered the other as well. The functional result was likewise satisfactory. At the end of a month the patient could flex and extend his joint within a range of 60 degrees to 70 degrees. The operation was successful despite the fact that only one articular surface had been covered with cartilage.”

“My intentions from the beginning,” says Dr. Lexer, “were to transplant upon both articular surfaces and I have done this.”

Dr. Lexer then operated upon a stiff elbow joint in a young woman. He transplanted thin disks of cartilage.

“After four weeks the dressing was changed and the elbow put up now in extension and then in slight flexion. Healing was perfect. Mobility began to become more extensive in the fifth week, when the patient left the clinic. She was extremely sensitive and afraid of pain during motion. The final result is not known.

“At the next occasion I proceeded another step forward and the desire to produce normal and normally covered joint surfaces led me to transplantation of an entire knee joint from a newly amputated lower extremity. The patient, an 18-year-old girl, suffered from bony anchylosis of the knee joint. The joint was fixed in acute flexion.

“A flap incision was made on the lower leg and the muscles and other tissues, together with a knee cap, were turned back so that the affected joint could be sawed out.

“The new joint was fitted into the defect,” says Dr. Lexer, “amounting in the extended extremity to the width of three fingers. It was obtained from a limb amputated simultaneously for senile gangrene, and consisted of both epiphyses with crucial ligaments and semilunar cartilages. Each epiphyseal portion measured about one and one-half fingers. Both projected laterally beyond the margins of the leg and thigh bones, and required trimming. Each was fastened with a nail.”

Following the readjustment of the soft tissues and the closing of the surgical wound, the leg was fixed in a plaster cast from the toes to the body.

“The cast,” continues Dr. Lexer, was interrupted from the middle of the leg to the middle of the thigh and bridged over by several iron bands. This allowed complete immobilization, combined with ready accessibility. The wound healed smoothly and the cast was removed after seven weeks and active movements begun cautiously. Extensive movements were opposed by renewed union between the knee cap and the femur. I decided upon a complete removal of the former, and for this purpose detached the lower half of the flap, about three months after the transplantation. All expectations were realized. The epiphyses were in firm union with the corresponding sawed surfaces of tibia and femur. The union was so complete that it did not offer even a trace of motion. The epiphyses were firmly healed beyond a doubt.”

Some Successful Cases

Dr. Lexer easily established the fact that the interposed joint was living and connected with the general circulation.

“A second transplantation for bony anchylosis of a tubercular knee joint was likewise successful,” says Dr. Lexer. “The entire knee joint was again taken from a freshly amputated limb. Technically the second case differs, inasmuch as the epiphyseal portions were not as wide as in the previous one, and wire was used for fixation instead of nails.

“Both cases show now (the first five months, the second nine weeks after transplantation) upon X-ray pictures excellent positions of articular surfaces and transplanted epiphysis. The operated extremities are somewhat shorter than the sound ones. The knee joint is usually in a position of normal extension. Lateral motion is present to a very slight degree in the second case; in the first one it has entirely disappeared. The patients can bear their weight upon the extremity during standing or walking without lateral deviation of the joint to either side. There is no pain while bearing weight.

“Operative improvement of unction could not be hastened, as liberal time allowance must be made for the healing of such extensive bone and cartilage transplantations. Frequent exercises within the limits of active mobility were ordered to strengthen the muscles and keep the joint active. Active motion is still considerably less than passive, on account of the contracted muscles.

“The possibility of organic incorporation of a transplanted joint taken freshly from man is proved. This promises well for the future.

“Other cases show that substitution of half a joint can be as easily accomplished as that of an entire joint. Tumors of bone are the causes for these operations.”

Dr. Lexer then describes the removal of the upper end of the chief leg bone for a cancerous affection and the substitution of a corresponding portion of a newly amputated leg.

“Here, again,” says the surgeon, “complete healing followed. The Roentgen picture shows at this date, five months after transplantation, that the articular surface of the tibial substitute fits well to that of the femur. Flexion as well as extension is nearly normal. On walking the patient finds support upon the operated leg. A thick callus has produced firm union of the substituted piece. At the end of two months the X-ray picture showed activity of the transplanted bone covering by production of new bone deposits in various places. In consequence there can be no doubt that the function of the knee joint will improve further and the endurance in walking will increase. The fact that the transplanted tibia was taken from the right leg to be placed into a left one led us to fear that the joint surfaces might fit badly and lateral mobility might ensue. This, strange to say, did not occur, perhaps on account of rapid rounding off after movements.

“In similar manner and with like success I substituted the upper two-thirds of the left upper arm bone. The lower portion of the thigh bone of an amputated limb was taken, as a disarticulated arm was not at hand. Here, also, uninterrupted healing took place. The patient is now commencing with active motion. Passive motion in the joint is extensive.”

In the same way Dr. Lexer substituted part of a man’s toe for part of a girl’s finger. Healing was perfect. The joints are movable.

“These operations enabled us,” says Dr. Lexer in conclusion, “by substitution of articular portions removed to preserve for the patients movable joints. In former times the result in the first case would have been a materially shortened limb with stiff joint by fitting the stump of the tibia into an opening in the articular surface of the femur.”

The claim of the world’s foremost surgeons and physicians is that by far the most important method of advance in medicine is by experiment. This in the human being, of course, is out of the question. Clinical observation, while very valuable, and indeed indispensable, never can be so exact as experimental investigation, because surgeons cannot open arteries and put tubes into them and conduct the experiments that they can on animals with the greatest accuracy as to blood pressure, study the effect of section of nerves, and so on.

All of this is done without the slightest pain to animals, and they receive the most antiseptic care, quite as much as any human being.

In this connection the investigations of Dr. George Crile of Cleveland and Dr. Cushing in reference to the prevention of shock are of great value. When surgeons have to amputate an arm or leg near the trunk, or when they have to extirpate tumors, for example, in the neck, large nerves have to be severed, and the cutting of these nerves produces very severe shock. This has been determined much more accurately by experiments on animals than by clinical observation on man, because the operator can accurately measure the fall in blood pressure and the irregularity of the heart’s action in animals which cannot be done in man.

Crile and Cushing then tried the effect of injecting a few drops of cocaine into the nerves just above the point where they were to be divided. It was then found that dividing these nerves after the injection of cocaine produced no shock whatever.

The elimination of this element in shock in a critical case very easily makes the difference between recovery or death.

Dr. Crile also has achieved some remarkable results in the direct transfusion of blood, similar to the method employed by Dr. Carrel. A woman suffering from cancer, which demanded operation, was in a very impoverished condition physically. When Dr. Crile was ready to operate he sutured the severed artery in the arm of the patient’s husband to a severed vein in the patient’s leg. Blood was allowed to flow during the progress of the operation. When the operation was finished the patient was found to be in a much better physical condition than when it was begun.

Dr. Crile has reported several more similar cases, and soon will publish a book on the subject.

Changing Heads of Dogs

Dr. C. C. Guthrie of St. Louis, who has been associated with Dr. Carrel in many of his experiments, describes in yesterday’s issue of the Journal of the American Medical Association some of the physiologic aspects of blood-vessel surgery. In this article Dr. Guthrie says:

“Briefly, the results so far have demonstrated the feasibility of transplanting limbs. That the restored circulation is adequate is demonstrated by the absence of gangrene or other symptoms attributable to this factor, both in the case of a hind leg replanted on a dog by Carrel and myself, and also by both fore and hind legs which I have transplanted from dogs to dogs of other breeds. In addition, I have transplanted dogs’ heads with preservation of cerebral and bulbar function. Even in a case in which the circulation was interrupted for twenty-nine minutes, good return of function was observed in the transplanted head. This demonstrated conclusively the adequacy of the restored circulation.

“Since I have found no evidence of serious derangement of metabilism (tissue change) in dogs’ thighs up to eleven days after transplantation, nor in a dog’s foreleg in six days after transplantation, and since there are no physiologic or other reasons known why such tissues as those found in the limb may not live and again function under such conditions, it seems justifiable to conclude that it is possible to transplant such a member with permanent success.

“It is now known that it is possible to transplant the legs or heads of dogs so quickly that perfusion (of blood) is unnecessary, coagulation not occurring under forty minutes to one hour or more, and the period of occlusion (shutting off of the circulation) requiring not over thirty minutes.”

The same publication of yesterday contains the following conclusions by Dr. I Carrel:

“It is proved that the remote results of the transplantation of fresh vessels can be perfect, and that arteries, kept for several days or weeks outside of the body, can be transplanted successfully, and that after more than one year the results remain excellent. It has been shown, also, for the first time, that transplanted kidneys functionate, that an animal, having undergone a double nephrectomy and the transplantation of both kidneys from another animal, can live normally for a few weeks, and that an animal which has undergone a double nephrectomy and the graft of one of his own kidneys can recover completely and live in perfect health for eight months, at least.

“Finally, it has been demonstrated that a leg extirpated from a dog and substituted for the corresponding leg of another dog heals normally.”

November 15, 1908

Doctor Describes Grafting of Cornea

It has already been announced by cable that Prof. Dastre had witnessed the successful experiment of grafting a cornea on the human eye, and now Dr. Magitot, who performed the operation, has made a communication on the subject to the Academy of Science. The communication is in the form of an essay which is entitled “The Possibility of Preserving in a State of Slackened Vitality for an Indeterminate Period the Transparent Cornea of the Human Eye.” The essay, which is a remarkable document, fully explains how the operation was performed and makes it clear that certain persons stricken with blindness may, by a similar operation, be able to see:

“The object of the present communication concerns the possibility of preserving the human cornea, and maintaining it outside the organism during an indeterminate period, and in certain conditions, with a sufficient vitality to allow of its being transferred to the cornea of the eye, one of the most delicate of tissues. It becomes glazed, and its epithelium is liable to desquamation very rapidly after life disappears, or after the eye has been removed. However, the experiments, which had already been published in the Annales d’Oculistique of 1911, enabled me to preserve its optical properties—that is transparency—and after a preservation of fifteen days to transplant it to another animal of the same species.

“My experiments on a human patient have been conducted in the same manner. A glaucomatose eye had to be removed on account of the intolerable pain which it caused. Sight in this organ had, moreover, been definitely lost for several months, but there had been such a hypertension that the cornea, in consequence of the interior pressure, had become insensible, and even opalescent. The entire eye immediately after its enucleation was bathed in a solution of Locke (a complex artificial serum) and then rapidly immersed in a flask containing sanguineous human serum procured from another person. The receptacle was without delay transferred to a freezing chamber, at a temperature of 22 degrees or 23 degrees Fahrenheit. In a few hours the internal pressure of the eye globe had fallen, and the cornea had recovered its transparency.

“This eye was preserved in excellent condition for eight days. At the end of that time a rectangular piece comprising half the thickness of this cornea was carefully cut out and transferred to a cavity of corresponding dimensions cut out of the cornea of another patient. This patient had some years before been accidentally burned in the face and in the right eye by quicklime. The consequence of this accident was that corrosive lesions of the eye were produced, and the cornea became opaque over almost its entire surface. The graft of the tissue, which had been preserved eight days, was put in place without any suture to the right of the pupil. The result was a little window of five by four millimeters, like a lookout opening pierced in a thick wall. The adhesion and the transparency of the transplanted tissue were perfect after forty-eight hours. It is now seven months since this transplanting was done, and not only has the foreign tissue been tolerated, but it has preserved its transparency, enabling the patient to have a visual acuity of one-tenth of the normal, which is more than sufficient for guiding one’s steps. Better still, the grafted tissue has manifested vitality in a more perfect manner by resisting the tissue of the cicatrice which formed around it, and which limits it without encroaching on its border. From this it results that the survival of the cornea is possible in man as well as in animals.

“Two conditions are necessary to obtain its maintenance in the state of slackened vitality. First of all, an appropriate medium is required, which is constituted by a hemolized serum of an individual of the same species. The hemolization should be obtained by purely physical means (such as a sudden fall of temperature by shaking warm blood in a receptacle cooled with ice). Secondly a feeble temperature is required, but not too low. The best temperature is comprised between 4 degrees and 7 degrees Centigrade. It should be a constant temperature, and variations, especially above 7 degrees, are detrimental. “We may find, therefore, that to the biological interest as regards the suspended vitality of a tissue so delicate as that of a cornea is added the practical interest for human patients. The transplanting of corneas, however, between different species, such as from dogs, rabbits, &c., is not successful. The piece so grafted is not long without losing its transparency. But we can preserve the material necessary for the transplanting and keep it in reserve for an opportune moment chosen for an operation. It is, therefore, to this extent possible to restore sight in a certain proportion of cases to patients stricken with blindness.”

January 28, 1912

Man’s Life Saved by Twin’s Kidney

By ROBERT K. PLUMB

The first known case in medical history in which a man’s life was saved because he happened to be one of a set of identical twins was reported here today.

At the annual meeting of the American College of Surgeons it was disclosed that a human kidney transplanted into a young man in Massachusetts last Christmas is still alive and appears to be functioning normally. The donor of the kidney was the victim’s identical twin brother.

Never before has such a feat of organ transplanting in man been accomplished. In no other known case in the history of medicine has a human kidney transplant “taken” and lasted so long. Attempts at transplanting other organs have not succeeded, either.

The report was made by Dr. Joseph E. Murray, Dr. John P. Merrill and Dr. J. Hartwell Harrison, all of the department of medicine and surgery, Peter Bent Brigham Hospital, Harvard Medical School.

Former Attempts Failed

In the past failure of kidney transplantings has been attributed to an “antigen-antibodylike” reaction. That is, the tissues of the host pour out disease-fighting antibodies. The antibodies attack the transplanted kidney just as they would any other germ material or “antigen.” Dr. Murray reported that recent microscopic studies of kidneys suggest that the kidneys themselves react strongly against the host.

Last December, Dr. Murray reported, one of the twins entered the hospital in a desperately sick condition. A kidney inflammation called glomerulonephritis had severely damaged both kidneys. He suffered high blood pressure, convulsions and other symptoms of profound kidney infection.

The patient, a 24-year-old single male, had an identical twin brother. Identical twins grow from one fertilized ovum, in distinction to ordinary twins, who, in most cases, are different individuals from different eggs, merely born at the same time.

3 Operations Performed

The evidence suggested that a kidney transplanting between identical twins might “take,” Dr. Murray said. Skin grafts between identical twins are successful whereas skin grafts between other individuals are not successful.

The ailing twin’s brother had two healthy normal kidneys. Many individuals who have lost one kidney lead normal lives because the other organ takes over the entire kidney burden.

The twins were placed in adjoining operating rooms last Dec. 23. The first operation took five and one-half hours. The left kidney was removed from one twin. It was sutured into the lower right side of the other. The kidney graft was without blood during the operation for an hour and twenty-two minutes. Arteries were sewn in place and the tube leading into the bladder was put in position. After it seemed that the kidney was going to do well, two other operations were performed to remove the damaged kidneys. The patient is reported now to be without symptoms, carrying on unlimited activity with no apparent disability.

November 3, 1955

Harvard Panel Asks Definition of Death Be Based on Brain

By ROBERT REINHOLD

Aspecial faculty committee at Harvard University has recommended that the definition of death be based on “brain death” even though the heart may continue to beat. The committee offered a set of guidelines for physicians to determine when such death occurs.

The 13-man panel was drawn from the university’s faculties of medicine, public health, law, divinity and arts and sciences.

The panel said its action was prompted by the possibility that “obsolete criteria” for death might lead to controversy in organ transplants and in modern resuscitative methods, which can maintain heartbeat in comatose patients with irreversible brain damage.

In a report, to be published today in the Journal of the American Medical Association under the title “A Definition of Irreversible Coma,” the committee urges physicians to accept new standards for determining the moment of death as a prelude to a change in the legal definition.

“We suggest that responsible medical opinion is ready to adopt new criteria for pronouncing death to have occurred in an individual sustaining irreversible coma as a result of permanent brain damage,” the report states. “If this position is adopted by the medical community, it can form the basis for change in the current legal concept of death.”

The committee was headed by Dr. Henry K. Beecher, the Henry Isaiah Dorr Professor of Research in Anesthesia at Harvard Medical School, who has written and spoken widely on medical ethics. In a telephone interview, Dr. Beecher said he did not believe that use of the committee’s criteria of brain death would cause physicians legal difficulties.

“Only the physician can pronounce death,” he said. “We think he can do it accurately on the basis of our criteria.”

Legally, in most states, death occurs when the individual is declared dead by a licensed physician. Basically, the criteria are irreversible cessation of respiration and circulation. However, the development of heart stimulators, respirators and other supportive devices have enabled physicians to keep the heart beating in persons in coma for two years or more.

As a result, a number of complex questions with ethical and moral overtones have arisen. Is it worth $30,000 a year to keep alive indefinitely a person with irreparable brain damage? Can society afford to discard the organs of such patients if they can be used to restore health to salvageable patients?

To facilitate solutions to problems like these, the Harvard professors set forth the following criteria to determine the characteristics of a permanently nonfunctioning brain:

• Unreceptivity and unresponsitivity—total unawareness of external stimuli and inner need; no vocal or other response to even the most intensely painful stimuli.

• No movements or breathing—one hour of observation is adequate to satisfy the criteria of no spontaneous muscular movements or breathing.

• No reflexes—the pupil of the eye will not respond to direct bright light; no eye movement or blinking; no swallowing, yawning or vocalization; tendon reflexes cannot be elicited as a rule.

The report said that a flat brain wave pattern, or electroencephalogram, was of “confirmatory value” in establishing brain death. It outlined the procedure for performing such tests for lack of brain activity.

Repeated Observations

All tests and observations should be repeated at least 24 hours later to confirm that there has been no change, the report stipulated. But it noted that the criteria could not be used if the body had been chilled below 90 degrees or if the central nervous system were affected by depressants, such as barbiturates. Patients have been known to exhibit flat electroencephalogram waves under such conditions yet revive later.

Once brain death is established, the report said, the family and all medical personnel involved should be informed; then the respirator supporting the patient should be turned off.

“The decision to do this and the responsibility for it are to be taken by the physician-in-charge,” the committee said. “It is unsound and undesirable to force the family to make the decision.”

The recent proliferation of transplant operations has underscored the problem of definition of death because organs must be kept viable after death. A controversy arose in Houston recently when the heart of Clarence Nicks, a murder victim, was kept beating mechanically for three hours after death had been declared. Such controversies would be obviated, Dr. Beecher said, if the Harvard criteria were accepted.

The report recommended that the decision to turn off the respirator be made by physicians not involved later in transplant of the patient’s organs—“to avoid any appearance of self-interest.”

An increasing number of medical men and others concerned with medical ethics and law have been urging that death be determined by brain damage. The question was discussed at the meeting last month of heart transplant specialists in Capetown. It also is to be the subject of a conference to be held by the American College of Cardiology next month in Bethesda, Md.

August 5, 1968

Transplant Frontiers: A Special Report: Healthy Give Organs to Dying, Raising Issue of Risk and Ethics

By DENISE GRADY

On a gray morning in Minneapolis, Tammy Hoff and Dormae Gebhardt sat in adjacent hospital beds making brave jokes with their husbands while waiting to be wheeled off to the operating room. It was a typical hospital scene, except for one detail: the two women, both in their early 30s, were perfectly healthy, and about to have major surgery that they did not need.

In another bed across the room was 31-year-old Kimberly Miles, Ms. Hoff’s sister and Ms. Gebhardt’s friend. Thin and pale, with oxygen tubing looped about her face, Ms. Miles, too, put up a bold front, kidding with her 8-year-old son and his father.

Unlike the others, Ms. Miles did need surgery, desperately. Her lungs were so damaged by the genetic disease cystic fibrosis that she had barely enough breath to walk across the room. She needed a lung transplant. But most transplants come from cadavers, and the waiting period for lungs is two years or more. Ms. Miles was not expected to live that long.

And so the three women cast their fates together. Ms. Hoff and Ms. Gebhardt each offered to donate half of one lung to Ms. Miles, whose own diseased lungs would be removed. The two donated halves would become her new lungs, smaller than normal but still large enough to let her live a normal life.

“She will walk and probably even run,” predicted Dr. Soon Park, her surgeon at Fairview-University Hospital and an assistant professor at the University of Minnesota Medical School.

Once unthinkable, using healthy people as organ donors to provide kidneys and portions of livers and lungs is gaining wide acceptance.

Ethically, emotionally and medically, this is uncharted territory. There is no doubt that living donors can save the lives of people who are languishing on transplant lists. But no matter how well the operations go, performing major surgery on someone who does not need it still violates the historical admonition that doctors must “do no harm.”

One live donor has died in the United States and others have suffered complications.

“The donors worry me a lot,” Dr. Park said. “Perfectly healthy people, having major operations. They are good people with a kind heart. Some donate and feel wonderful. Others may donate, go through a big operation and the recipient dies. We are creating questions I don’t have answers for.”

Dr. Park himself donated a kidney to his ailing sister while he was a college student.

The very existence of these operations forces patients and their relatives to look within and confront their fears, values and feelings about themselves and each other. Patients must decide whether they can bear to ask a relative or friend to endure the pain and risk of major surgery on their behalf. An organ is a gift that they will never be able to repay. And the friends and relatives must decide whether they are willing to put their own health on the line. Some learn things about themselves that they might have preferred not to know.

“Whether you say yes or no, it will affect you for a lifetime,” Dr. Park said.

Increasingly, surgeons are telling people who need transplants that their relatives, spouses and friends are potential organ donors. In most cases, the recipients’ insurance pays the medical expenses of donors. Hospitals are setting up education programs and support groups for potential donors and recipients. The existence of the surgery has created a pressure on families that did not exist before. In some cases people as young as 19 are being asked to act as liver donors for their parents.

Fueled by the severe shortage of organs from cadavers, the number of living donors in the United States rose by 16 percent in 2000, to 5,500, the largest increase in any one year. Most donors gave a kidney, an operation that has become routine and provides 40 to 50 percent of kidney transplants.

Although ethical objections were raised about living kidney donors when the practice began, the operations have become so safe and are so successful that they are not questioned today.

But liver transplants from live donors require a far more complicated and risky operation, removing part of the organ. Nonetheless, these transplants have increased sharply, to 347 in 2000 from 86 in 1998. In New York State last year, a third of all liver transplants came from live donors. And the number of live donors for lung transplants—also riskier than kidney donation—has slowly grown in the last decade, though each recipient requires two donors.

The vast majority of the operations have been successful. But no surgery is without risk. Aside from the liver donor who died in the United States, several others are reported to have died in Europe. But none of the deaths have been written about in medical journals, and no one is certain of the number. Doctors estimate the risk of death to liver donors to be 10 to 20 in 10,000 compared with 3 in 10,000 for kidney donors.

The shift to living donors is a major change in the history of transplants, and it is happening quietly, on its own, with no centralized control. Unlike drugs, new operations do not have to be approved or regulated by any government agency or medical group, so individual hospitals make their own decisions about whether to go ahead with live donor programs. In a sense, the expanding use of live donors is a vast scientific and social experiment.

“There is no Food and Drug Administration for surgeons,” said Dr. Jay Hoofnagle, director of the division of digestive diseases and nutrition at the National Institutes of Health. “So procedures just get adopted.”

Given the rapid growth of the field, some doctors are troubled by the lack of formal control over the operations and the lack of long-term follow-up and reporting on the donors. Different doctors use different surgical techniques, and there have been no major comparative studies to determine which work best. There are no mandatory registries to keep track of donors or complication rates and no means of certifying transplant programs.

Pressure of Donating: Facing a Relative Who Is Facing Death

Wendy Marx, a 34-year-old woman in San Francisco who has had two liver transplants, both from cadavers, said her doctor suggested that she consider asking a relative to donate if she ever needed a third transplant. Ms. Marx said she found the idea very disturbing.

“It’s not right,” Ms. Marx said. “You have to think of the worst-case scenario. If I woke up and found out that my mother or brother had died so that I could have a transplant, I wouldn’t want to be alive.”

Her husband strongly disagrees, Ms. Marx said, and she conceded that if she were facing death she might feel differently.

Transplant teams say that they never ask anyone to donate and that donors must come forward on their own. But of course, they cannot know what was said at home before the donor came forward.

Some doctors are reluctant as a matter of principle to take organs from live donors. Some doctors worry, too, that even though donors and recipients are screened by psychiatrists and social workers and evaluated by different medical teams to avoid conflict of interest, donors may not truly be acting freely. They may be caving in to pressure from the recipient and other family members, and blinded to the risks by their own guilt and distress over seeing a loved one suffer.

Those who have never had major surgery may have no idea how difficult and painful it can be. In any case, a relative’s fatal illness itself can be coercive, evoking a powerful sense of obligation and the feeling that to say no is to let the patient die without trying to help.

Dr. Myron Schwartz, a liver transplant surgeon at Mount Sinai Hospital in Manhattan, said, “I often wonder how well prospective donors hear the risks we tell them about.”

Dr. Richard J. Battafarano, a lung transplant surgeon at Washington University in St. Louis, said: “You can imagine, you have a sick child that’s been told if they don’t have a transplant they’re going to die, and all of a sudden all the family members are looking at one another to see who’s a match. Even if it’s not spoken, there’s a lot of pressure.”

But if doctors disagree with someone’s decision to be a donor, do they have the right to refuse to operate? The answer is not always clear. At one hospital, when a young man offered to be a liver donor for his mother, surgeons rejected him because he had a baby. At another hospital, a similar donor was accepted. Surgeons say they are sometimes torn between their needs to protect donors and to respect the donors’ rights as adults to make their own decisions.

Liver Transplants: Few Children Now Die on Waiting Lists

The first live donor liver transplants were from adults to children, and the procedure, which grew rapidly in the 1990s, has unquestionably been a great boon. Before it came into use, 20 percent to 30 percent of children who needed livers died on the waiting list. Now, hardly any do. Many receive livers from their parents or other relatives. Around the world, more than 1,500 pediatric operations with live donors have been done.

To provide a transplant for a child, doctors remove all or part of the left lobe of the donor’s liver, the smaller of its two lobes, making up about 30 percent of the organ. Because the liver has an extraordinary ability to regenerate, the donor’s liver grows back to its normal size within a few weeks, and the transplanted piece also grows with the child.

Initially, surgeons took a cautious approach to liver transplants for children using live donors, and they did not begin performing them until the operations had been studied and proved to work by doctors at the University of Chicago, in 1991. But that wariness did not extend to adult-to-adult transplants, even though they require a much riskier procedure, removing the right lobe of the donor’s liver, 50 to 70 percent of the organ. Instead, the surgery caught on quickly, before anyone had a chance to do a detailed study. Although no one questions the use of live donors for children, using them for adults is controversial.

Dr. Hoofnagle said: “The adult operation is different from the pediatric one. It’s a big step. Ethically, you’re no longer talking about parents and child, the image of a child in a burning building. This is not a child anymore. Sometimes it’s a parent who’s 60 years old. It’s a very different level of ethical decision. The operation is much bigger. You are right at the edge of putting someone into liver failure. In fact, in the immediate post-op period the donor is suffering from borderline liver failure. It’s tenuous.”

In May, Dr. Mark Siegler, a medical ethicist who was involved in planning the pediatric clinical trial of liver transplants in Chicago, joined two liver surgeons in writing an article in the New England Journal of Medicine that criticized the rapid expansion of live donor programs for adult liver transplants and called for government control. They said that although the operations were extremely valuable, too many hospitals in the United States were doing them or planning to start, including some centers that might lack the experience needed to perform the operations safely. And they suggested that some surgeons and medical centers that were starting to do the operation might have been motivated in part by the desire for prestige and money.

Dr. Siegler and his coauthors also questioned whether all serious complications and deaths among donors were being reported.

“I suspect that if we had full reporting of the complications and mortality of the operation from the U.S. and Europe, we would discover that there are more complications and additional deaths that have been thus far unreported,” Dr. Siegler said in an interview.

The one donor death known in the United States occurred in July 1999, at the University of North Carolina. The donor was a 41-year-old man, Danny Lee Boone, who suffered complications and died three weeks after donating a portion of his liver to his half brother, who survived.

Other problems have occurred. At a meeting last fall of medical social workers specializing in liver transplants, one participant described a case in which the recipient died and the donor, his brother, began drinking shortly after the surgery. His liver did not regenerate fully, and he refused treatment and broke off contact with the doctors.

In a similar case, described by doctors at New York Presbyterian Hospital in Manhattan, the recipient was a woman with fulminant liver failure, a type that comes on suddenly and is fatal in 48 hours without a transplant. A much younger relative became the donor, but had far less time than most donors to think over her decision. The recipient died. The young relative became depressed, not only because of the death, but because she herself had gone through a painful operation and felt disfigured by the big abdominal scar it had left, while nothing had been gained. She, too, stopped seeing the doctors, and the hospital team decided not to use any more live donors for patients with fulminant liver failure.

Doctors said they had encountered cases in which desperate, frightened parents tried to pressure their own adult children into acting as donors for them. Dr. Silvia Hafliger, a psychiatrist at New York Presbyterian Hospital, said one woman called her daughter every day, begging her to be a donor, even though the daughter had just had a baby. The young woman did not want the surgery, and Dr. Hafliger said she urged the mother to let her daughter alone.

“I yelled at her,” Dr. Hafliger said. “I said, ‘How could you even think of that?’”

Children donating livers to parents are surprisingly common, and the process brings up difficult issues for some families. This is particularly true if the cause of the failure has been hepatitis C, the leading reason for liver transplants in the United States. Many people with the disease contracted it long ago through drug abuse, which they never revealed to their children. During transplant discussions, the secret inevitably comes out, and both donor and recipient must decide whether it is fair to ask someone else to give up an organ in those circumstances.

Similar questions come up when the recipient’s liver disease resulted from alcoholism, particularly if there are doubts about the recipient’s ability to stay sober.

Every transplant group has encountered people who volunteer to be donors but who, away from their families and alone with a doctor or social worker, reveal that they actually do not want to go through with the surgery. Some do not fully realize it themselves until they begin discussing it, and most are ashamed to admit it to their families. Most medical teams help cover for them by telling relatives that they were medically unsuitable but not specifying why.

At the social workers’ meeting last fall, one participant said he felt he had really done his job when potential donors declined, not because he had talked them out of it, but because he had helped them decide what they really wanted to do.

Another participant, Carol Holzer, from New York Presbyterian, said there was a constant tension between social workers and surgeons because the surgeons were eager to operate and the social workers were eager to pick up signs of ambivalence and rule out reluctant donors.

The Rewards: Painful Recoveries Don’t Dim Elation

For people with cystic fibrosis, the age of 31 can be close to the end of life, and Kimberly Miles’s past two years had been a constant struggle. She spent more and more time in the hospital with lung infections and could no longer breathe without supplemental oxygen. In April 2000, at her mother’s urging, the family began considering a live-donor lung transplant. Family members volunteered, but Ms. Miles’s parents, her cousin and one sister were ruled out for medical reasons.

The sister, Debra Bloczynski, 38, said: “You have mixed feelings. You love her and you want to help. But you think about yourself. You want to do it and you don’t.”

The idea that anyone could have mixed feelings about being a donor angered Ms. Miles’s mother, and Ms. Bloczynski said she felt guilty that she had not qualified. So did the cousin, who referred to herself as “the big reject.”

Ms. Miles’s friend, Dormae Gebhardt, meanwhile, said she decided instantly to volunteer. But Ms. Miles’s other sister, Tammy Hoff, hesitated, all the while feeling considerable pressure from her mother.

“It was not easy,” Ms. Hoff said. “I had mixed emotions.”

Members of the transplant team sensed her ambivalence and rejected her. She grappled with her feelings for a month, then decided to go ahead. She met with the team again and was accepted.

“You have to decide, and when you do you feel a lot better about yourself,” Ms. Hoff said. “What actually got me was when I went to a checkup with Kim. There were these people that had had cadaver transplants, and this one lady had this look in her eye that said, ‘Just do it.’ It was like she was some kind of guardian angel, like a sign from above that said, ‘Do it. It’s going to work.’”

Lungs for transplant are difficult to obtain, because they can be harvested from only 10 percent to 15 percent of cadaveric organ donors. Often, infection or other conditions make them unusable, and the scarcity has led surgeons to turn to live donors.

Surgeons say that donors recover fully and rarely feel different than they did before the surgery.

A report last year on 62 lung donors at Barnes-Jewish Hospital in St. Louis showed no deaths, but many had complications after surgery. The authors of the study concluded that the operation should be done only on patients who could not wait for cadaver transplants, and that donors must be warned about the high rate of complication.

The St. Louis doctors found that 38 of the 62 donors, or 61 percent, had complications, including 12 major problems and 55 minor ones. The major complications included a hemorrhage that required transfusions and a nerve injury that partly paralyzed a patient’s diaphragm, though it did not cause symptoms or other problems. In another case, the surgery caused an abnormal heart rhythm and the patient needed a procedure to destroy damaged nerve fibers that were disrupting his heartbeat. Another patient had two lobes removed from his right lung instead of one, because of a surgical problem.

The minor complications included pneumonia, temporary problems with heart rhythm and infections of the pericardium, the sac around the heart.

“Our feeling was that we wouldn’t expand the use of the procedure,” said Dr. Battafarano, the lung transplant surgeon who was an author of the paper. “This review confirmed our view that we should reserve it for recipients who have no alternative. And that has to do not only with the donor operation but also that if the recipient can survive on the list, they’ll get two full lungs.”

The extra tissue from a cadaver, he said, could lengthen survival.

Dr. Park said that the chance of death for donors was very small, and that he had not heard of any deaths in lung donors. “But that’s biased,” he said. “If it happened, people would not be likely to brag about it.”

For people with cystic fibrosis, a lung transplant offers a 75 percent chance of living one year and a 65 percent chance of living five. To Ms. Miles, who had been hospitalized for four months before the surgery, those odds sounded pretty good.

“Her ability to survive outside the hospital is nonexistent,” said Jackie Zirbes, a transplant coordinator.

On the morning of the surgery, three operating rooms and three surgical teams, about 25 people in all, were ready. And as the surgeons required, a backup donor, another friend of Ms. Miles, stood by, ready to be taken into surgery in case doctors found that they could not remove a lung section from one of the primary donors.

Ms. Hoff’s operation, a three-hour procedure to remove the lower lobe of her right lung, began first. After about an hour, when it was clear that the lobe could be taken out, doctors began to remove Ms. Miles’s right lung. Replacing both her lungs was expected to take about six hours.

While Ms. Hoff’s lobe was being sewn into Ms. Miles, doctors began to remove Ms. Gebhardt’s. By late afternoon, Ms. Hoff and Ms. Gebhardt were in recovery. And Ms. Miles’s new lungs were in place. They puffed up like balloons to fill her small chest, to the delight of the surgical team.

Ms. Miles recovered slowly but surely, despite a bout with pneumonia shortly after the surgery. Her new lungs worked well, she was freed from her tether to an oxygen tank and she was able to return briefly to her home in Black River Falls, Wis. But other problems set in, possibly related to her cystic fibrosis, which affects the digestive system as well as the lungs. Since the transplant, Ms. Miles has suffered from such severe nausea and vomiting that she has been unable to eat and has required a feeding tube. She was back in the hospital for gallbladder surgery by early June and remained there yesterday.

Ms. Hoff and Ms. Gebhardt recovered quickly, though with far more pain and fatigue than either of them had expected. Two months after surgery, both were back at work full time. Six months after the surgery, both were reported fully recovered by their surgeons.

Ms. Gebhardt said that giving up a few weeks of her life seemed a small price to pay for the chance to add years to Ms. Miles’s life.

“Even with the pain I had to go through, I would do it all over again if I had to,” she said.

In the weeks after the surgery, Ms. Hoff was delighted to see the changes in her sister. “Her cheeks are rosy, her eyes have a little glitter, her fingertips aren’t purple anymore,” Ms. Hoff said. But, she added, “She’s got a heck of a road to go.”

As for herself, Ms. Hoff said: “I have no regrets at all. It’s a scar you’re proud of.”

June 24, 2001

French, in First, Use a Transplant to Repair a Face

By LAWRENCE K. ALTMAN; with reporting from CRAIG S. SMITH

Surgeons in France have for the first time performed a partial face transplant, a surgeon who led one of the two teams that performed the operation said yesterday.

The recipient of the transplant was a 38-year-old woman who had been severely disfigured in an attack by a dog, said the surgeon, Dr. Jean-Michel Dubernard of Lyon. The operation was carried out in Amiens on Sunday.

In a brief telephone interview, Dr. Dubernard said the two surgical teams had grafted a nose, lips and chin from a donor who had been declared brain dead onto the woman’s face.

Hospital officials said the woman who received the transplant did not wish to be identified. They gave no details about what measures, if any, had been taken to reconstruct her face short of a transplant. “The patient is well and fine, and the graft is O.K.,” Dr. Dubernard said. He said a news conference would be held tomorrow in Lyon to discuss the case.

The surgery represents the first foray into a much-debated realm of medicine. A number of other surgical teams in the United States, France and the Netherlands have announced plans to perform various types of face transplants. But none are known to have performed the procedure. Face transplants are among the most disputed frontiers in transplantation science because they are so risky and no one can say what a patient will look like afterward.

Ethics committees in France and England have rejected proposals to perform full face transplants until more research is done. The committees were concerned about the unknown risks of the long-term use of large doses of immunosuppressive drugs for a procedure that does not save lives. The aim of face transplants is to improve the quality of life for patients who have suffered severe injuries from burns, accidents and shootings, for example.

The French committee did approve partial face transplants of the type performed on the woman in Amiens. But the committee cautioned in a report last year that even a partial transplant—the mouth and the nose, for example—was “high-risk experimentation.”

In the United States, an institutional review board that oversees the safety of human experiments at the Cleveland Clinic last year became the first such body to approve a full face transplant. Full and partial face transplants can involve the transfer of attached muscles, blood vessels, nerves and other tissues. The tissues are needed to help restore an acceptable appearance for the recipient.

Among the risks of either type are the chance that the graft will be rejected, leaving a patient in a worse condition than before the operation, the development of cancer from the immunity suppressing drugs given to prevent organ rejection, and the chance that a patient will suffer psychological problems in adjusting to a new identity and appearance.

The woman who received the transplant on Sunday had been attacked by a dog last May. Dr. Dubernard said she was transferred on Tuesday from Amiens to the Edouard-Herriot Hospital in Lyon, where Dr. Dubernard works, for long-term monitoring of the immunosuppressive therapy that she will need. The transfer was according to a scientific blueprint that Dr. Dubernard said he and Dr. Bernard Devauchelle of Amiens had agreed on before the operation. He said Dr. Devauchelle’s team was “very well trained for this type of surgery.”

In 1998, Dr. Dubernard headed the team that performed the first hand-forearm transplant. He is also a politician and member of the French Parliament.

Outside experts said it was difficult to know whether the partial transplant was as difficult to perform as a full face transplant. For example, it is not known how badly injured the woman was, or how much of the donor’s face and underlying muscle, blood vessels and tissue were transplanted Sunday. Also, the experts said they could not determine how well the French team had informed and prepared the woman psychologically for the transplant.

The relatively short interval of about six months between the dog bite and the surgery raised questions among some experts about what, if any, efforts had been made to perform reconstructive surgery first. “The major question is: what were the indications” for the transplant, said Dr. Maria Siemionow, a surgeon at the Cleveland Clinic who plans to perform a full face transplant.

Questions about the timing of the French surgery are relevant because the first patient to receive a hand transplant, Clint Hallam, did not comply in taking his prescribed antirejection therapy. He had his transplanted hand amputated in 2001, three years after receiving it.

Dr. Laurent Lantieri, a surgeon who was not directly connected with the French woman’s surgery but who has reviewed some of her records, said he was puzzled about why she was put on the list for a face transplant in June or July, so soon after she received her injuries. Dr. Lantieri has published articles about his intention to perform partial face transplants, and was a consultant to the ethics committee in France that approves such procedures.

Face transplants, the committee said, should not be performed on an emergency basis. One reason, it said, is because “the very notion of informed consent is an illusion,” even if all standard techniques have been exhausted, a candidate patient insists on receiving the transplant and a donor is available. “The surgeon cannot make any promises regarding the results of his restorative efforts, which are always dubious,” the committee said. The report continued, “Authentic consent, therefore, will never exist.”

The national committee was intended only to give advice and not to approve individual cases, Dr. Lantieri said in a telephone interview. French surgeons are supposed to have their experimental protocol reviewed by an independent committee of experts before carrying out a partial face transplant, he said.

Dr. Lantieri said he had reviewed a summary of the woman’s medical record and examined a photograph of her damaged face. The woman’s type of injury seemed consistent with proposals to do a partial facial transplant, he said. “She had very strong psychological problems,” Dr. Lantieri said. “I said I would not go further if I did not have more examinations by additional psychiatrists to know that she would be able to pursue lifelong immunosuppression therapy.” Dr. Lantieri said he believed that Dr. Dubernard “wanted to be first” to do a face transplant, as he had done a hand transplant.

Dr. Dubernard said his team planned to do another transplant—of bone marrow—on the woman while she was in the hospital in Lyon. Although bone-marrow transplants are a standard treatment for some conditions, in this case the hope would be that it would increase the patient’s tolerance to a graft.

Dr. Lantieri said if a bone-marrow transplant was carried out on the patient it would mean that she would be undergoing two experiments at the same time. The extra experiment would be unethical, Dr. Lantieri said, because “every ethical committee says that only one experiment should be carried out at a time. That is a basic rule of clinical research.”

But, he added, “I really hope the partial face transplant will work.”

December 1, 2005