Nine

SURGICAL EXPERIMENTS

1. BURNS

Number and Type of Experiments

Everyone has experienced the pain of thermal burns, so naturally the thought of experimental burns affecting animals is very disturbing. The first question that comes to mind is: how numerous are these experiments?

Since government regulations do not call for a breakdown of the nature and purpose of experiments reported under the Animal Welfare Act, and since the government-supported National Research Council has failed to supply this information in its broader surveys of animal research, it is impossible to quote statistics of burn experiments for the U.S. However, Great Britain does produce some figures on this subject in the reports presented annually to Parliament by the Home Office. (UK Home Office,1978). A summary may be of interest.

The figures cited in Table 1 are for the year 1977. An animal is counted as one experiment, and an experiment involving a number of animals is counted as many times as there are animals experimented upon.


Table 1. Burning or Scalding Experiments on Living Animals
in the United Kingdom in 1977. (UK Home Office, 1978)
*Exposed to ultraviolet rays simulating sunlight.


If burning and scalding experiments are one-twelfth of one percent of the British total, the same percentage of the estimated 100 million American experiments (Fox, M., 1979, p.15) would total about 120,000. The British statistics reveal that some 80% of the burn experiments involve the study and development of pharmaceutical products - presumably drugs designed for use in. the therapy of burns, although sunlamps may also be included in this group. The 2,120 experiments which were conducted, without anesthesia, testing ultraviolet light burn, must have been part of this 80% and must chiefly have had to do with the evaluation of anti- sunburn products and with the many drugs which, even when taken internally, are photosensitizers; i.e., cause skin reactions in sensitized persons exposed to sunlight.

Although some of this pharmaceutical research may get into the pharmacological journals, much of it is probably in-house research and not reported in the literature. However, an occasional reference in compliance with the Animal Welfare Act may appear in an annual report of one of the drug companies; e.g., Johnson and Johnson's description of 52 burn experiments in rats, with the comment: "No postoperative analgesics were used because it would interfere with experimental results." (USDA/APHIS,1973, Johnson & Johnson Res. Foundation).

Postoperative Analgesia Is Often Inadequate

To inflict a burn on an animal inevitably produces pain and usually much postoperative suffering. One would expect that those undertaking such distressing procedures would try to relieve their subjects through the use of carefully chosen anesthetics and analgesics. It is true that all the acute burning is done under anesthesia. In a group of three experiments involving guinea pigs, all conducted by Robert Wolfe and associates at Louisiana State University Medical Center and at Harvard Medical School, the following anesthetics were used:

1. "Whiffs of halothane before being burned and for approximately 5 min. afterward which was long enough to ensure that they felt no pain (as indicated by the absence of squealing) before lapsing into shock."
2. "Whiffs of halothane."
3. Halothane (2% halothane in 100% oxygen).

But none of the above (nor other burn experiments I have reviewed) refer to effective postoperative analgesia or tranquilizers. Apparently, these are not supplied, and no doubt if the experimenters were asked why, the reply would be that the drugs might affect some of the physiological functions under investigation.

What about the whiffs of anesthetic gas continued for five minutes post- burn in the guinea pig experiment No. 1 above? The burns were produced by a three second immersion in boiling water. Ten animals were burned over 70% of their body surface and seven of them died within 24 hours. Another seven were burned over 55% of their body surface and all survived over 24 hours. The purpose was to study cardiovascular and metabolic responses during burn shock, but without employing anesthesia deep enough to alter the response to the shock resulting from the intense burn. Accordingly the animals were given "whiffs" of halothane sufficient to prevent squeals of pain, but lasting only five minutes and therefore not long enough to affect the physiological functions being monitored. This cannot be considered effective postoperative analgesia: after the initial shock had passed - with some animals surviving into the second day - it seems certain that pretty severe suffering must have been the lot of many of them, if not all. (Wolfe, R.,1976).

In another experiment a few months later, Wolfe and his associates partially immersed 26 guinea pigs, "temporarily anesthetized with whiffs of halothane," in boiling water for three seconds. Nothing is mentioned here about prolonging the anesthesia to avoid squealing; however, the animals all died between 8 and 24 hours post-burn. Various physiological functions were studied, and the results indicated "an important role of lactate in burn shock metabolism." (Wolfe,R.,1977a). In a third experiment, Wolfe and J.F. Burke produced a third degree burn by a much longer immersion (20 secs.) of 16 guinea pigs in boiling water, using 2% halothane in 100% oxygen. Five animals died between 60 and 72 hours post-burn, eleven survived more than 72 hours. (Wolfe, R.,1977b).


Further Examples of Burn Research

Other investigators, experimenting on rats using other than halothane anesthesia, also reported burns produced by partial immersion in boiling water or steam. No postoperative analgesia was mentioned. The purposes and findings were briefly as follows:

W.L. Brown and associates studied protein metabolism in rats who had been burned, and in others who had been burned and whose wounds were then seeded with the organism P. aeruginosa, source of an infection which is a major cause of death in severely burned humans. They discovered that the post-burn drop in concentration of the body's serum albumin is due to the large pool of this protein which forms in the wound area. (Brown,W., 1976).

J. Turinsky and colleagues found that a 20% surface burn injury in the rat is followed acutely by a brief period of glucose intolerance, succeeded by a much longer phase in which there is a secretion of large quantities of insulin, indicating that the hormone is striving to overcome some physiological resistance. The source of the resistance has not been determined. (Turinsky, J. 1977).

George Noble and associates burned 100 rats, followed by various procedures to determine the effect of heparin (which prevents blood clotting) on the vasculature of the wound and surrounding tissues. Heparin, given before the burn, was found to retard the devitalization of the blood vessels; given afterward, it had no effect. (Noble, H.,1977). This was a joint project of the University of Chicago Pritzker School of Medicine and the Yale University School of Medicine.


Repeated Burn Experiments on Sheep

Although guinea pigs, rats and mice seem to be the preferred species for burn experiments, R.H. Demling and associates at the Burn Unit of the University of Wisconsin Center for Health Sciences have experimented on sheep. Twenty-eight sheep were anesthetized with pentobarbital (10 to 15 mg/kg intravenously). A hind limb was scalded in 850 to 950C. water, causing second to third degree burns. The second hind limb of each animal was burned in the same manner a week later, and heparin was injected at various times and in different doses to study its effect on edema (lymph leakage) in the flesh of the wound area. It was found that heparin did not have a beneficial effect on the edema. (Demling, R.,1979).

The fact that a second painful procedure was performed on each of these sheep just when it was recovering from the first may raise a question in the reader's mind. Is this humane? Known as "multiple-survival surgery," this practice, according to the National Institutes of Health "Guide for the Care and Use of Laboratory Animals" (which sets standards for research), is generally to be discouraged. However, the Guide goes on to say that such procedures may be permissible under certain conditions, including aftercare to alleviate postsurgical pain and when the operations "are related to components of a research or instructional project." (ILAR,1978,p.14). Since the experimenters make no mention of postoperative analgesics, one cannot be sure that the first condition has been met, but the fact that the repeated burning is part of the same experiment fulfills the second requirement, although it is doubtful whether this makes the sheep feel any better. Probably the Guide seeks primarily to discourage veterinary students or surgery interns from practicing a series of haphazard procedures on the same animal, accompanied by the careless aftercare which is the usual hallmark of group callousness and irresponsibility.

Synthetic Substitute: "Thermo-Man"

In order to study the way garments of different materials ignite and transfer heat under varying conditions, the Du Pont Company has been experimenting with "Thermo-Man," a life-sized dummy made of epoxy-fiberglass resin, implanted with 122 sensors. These detect temperature at a given time; and through a skin-simulating computer program, the actual heat transferred from a burning garment and the depth of thermal injury (first, second or third degree burn) can be calculated for human skin. The computer program is sophisticated enough to account for the liquid to-vapor phase change that occurs at 100oC. in skin-tissue water, and a controlled wind system can simulate Thermo-Man in motion.

Excellent correlation has been demonstrated between Themo-Man burn damage information and that obtained from injuries in humans and in experiments on pigs. (Bercaw, J., 1977).


Non-survival Experiments on Animals

Critics of the use of animals for experimental purposes have been known to describe procedures which sound horrifying, such as dipping dogs or monkeys in boiling water, without always specifying whether the animals actually suffered pain. But if the animals have been anesthetized throughout the experiment, and are never allowed to recover consciousness, the procedure itself cannot properly be called inhumane. With Thermo-Man only the effects of very intense heat - as from a flash-burn - can be demonstrated: there would be acute destruction of skin tissue in vivo. But when anesthesia can be prolonged for hours, in non-survival experiments, secondary changes can be studied in the skin and even in other organs.

As an experiment with serious intent to contribute to burns research, and one in which animals did not suffer, I cite an investigation at the University of Gothenburg, Sweden, to study the effects of thermal injury on circulation and respiration in dogs. Seventeen dogs were used, and the burn was produced by immersing the rear half of the body of the ketamine- anesthetized animals under water at 800C. The anesthesia was maintained by hourly infusions until the dogs were killed six hours later. The experiment yielded information about the effect of burnproduced denatured proteins on other components of the dogs' blood, and especially on one known as "complement." Although this substance helps in scavenging damaged and coagulated cells, it can also overact and cause hurtful side effects on the lungs and cardiovascular system. (Heideman, M.,1979).

Human Cell Cultures

Although skin cultures (epidermal cells) have been developed (Nardone,R.,1977), and cadaver skin is also available, burns research is largely concerned with the physiology of the whole organism, not merely with the traumatized skin. The use of in vitro techniques such as cell and organ cultures in this field is therefore rare. However, it will be recalled that in the British statistics (cf.p.146) almost a third of the experimental burns reported involved exposure to ultraviolet rays, although admittedly these were not considered Painful enough to require anesthetics. An experiment at the Laboratory of Radiobiology, Harvard University, may be of interest in this regard. Williams and Little pretreated a culture of human cells exposed to lethal effects of ultraviolet light with the drug proflavine. These cells showed a significant enhancement in survival compared to untreated cells. The authors suggest that their cell culture technique could lend itself to an investigation of the various "photoproducts" induced in cells by ultraviolet light, and the role these photoproducts play in the effects observed in irradiated cells including cell death, mutation and transformation. (Williams, J.,1977).

Theoretically, it seems possible that the effects of toxic products of thermal burns from human patients might also be investigated in human tissue or organ cultures. If these cultures were kept alive and differentiated in some of the sophisticated media now available, the period of observation could be prolonged into days and weeks, thus reaching the third stage in the time scale of acute, subacute and chronic alternatives.


Postoperative Pain-relief

Since burns research concentrates ultimately on the physiology of the whole organism, such matters as the balance and distribution of fluids and electrolytes, the status of the vascular system and the blood, the degree of pain and shock, and the systemic reaction to drugs are all of vital importance. Although much has been learned from study of the human patient, there are still unanswered questions which impel investigators, with the approbation of most of the public, to turn to the animal model, with all organs intact and interacting, and without the obvious limitation of in vitro cultures. And a longer period of study is often required than is possible with the animal under general anesthesia in a non-survival experiment.

Recognizing, therefore, that such research will inevitably continue, we must concentrate more on the animal's pain and ask, can this be relieved if not eliminated?

First of all, the experimenter should give more recognition to this pain. When a human is burned, much attention is given to pain: to the reactions it may stimulate in the patient through the nervous and endocrine functions under its control, and to
its relief by drugs. To ignore similar reactions in suffering animals, or to sensibly increase the suffering by withholding pain relief, may add to the difficulty of comparing the effect of the trauma in animals with that in humans (or compound the difficulty which already exists owing to species difference). The many physiological reactions of an animal in fear and pain enumerated by Harold Hillman (cf.p.14), apparently ignored by many investigators, are, according to Hillman, "almost certainly the main reason for the wide variation reported among animals upon whom painful experiments have been done." Possibly this may explain the confused results reported in the Noble and Demling experiments (cf.p.1.50) on the effect of heparin, which are in conflict with earlier studies of the action of this drug. These unexplained variations in findings always result in repeated experiments and the sacrifice of more animals. Demling concludes his paper with the words, "Further studies are necessary...."

Secondly, the experimenter should give pain relief throughout the experiment comparable to that offered a human patient. Comes the objection: pain- relieving drugs must be minimized or withheld because they alter the physiological functions of the animal and may "defeat the purpose of the experiment" (a stock phrase parroted from numerous official research guidelines).

This glib response spells indolence, ignorance, and inhumanity. There is a perfectly good way to assess the effects of any pain-relieving drugs which might be used: namely, by running a control series of animals which would not be subjected to the burn but would receive the anesthetic and/or analgesic. In this way, any variations in the physiological status of the animal caused by these drugs could be noted, and could be taken into account when other parameters were being evaluated. As it is, control animals are always included in these investigations, and this suggestion would simply add more of the same.

This should lead to more and probably much needed knowledge about the effect of anesthetics and analgesics generally and clarify some hitherto inexplicable variables. Interestingly, one of the anesthetics used in several of the above-mentioned experiments, halothane, has been studied in rat cell cultures, yielding information about its influence on protein and lipid synthesis. (Ishii, D., 1971).

A complementary approach to the study of these drugs is through mathematical modeling and the use of digital computers. Thus in an article entitled "Simulation as an aid to the replacement of experimentation on animals and humans," R. and M. Harrison discuss the value of computers in predicting the effects of drugs and combinations of drugs in various dosages. (Harrison, R.,1978). Unfortunately, many experimenters are ignorant of these techniques, but that is a poor excuse for a lack either of humaneness or scientific precision. Essentially, the investigator in these burn experiments needs to know the effects on body chemistry of various drug inputs. Here the computer can help by simulating the behavior of human blood at steady-state equilibrium, then reflecting it under various simulated stresses. And its ability to simulate the respiratory system could be valuable in conjunction with studies of anesthetics made on the living animal. (Maloney, J., 1963).

2. DRUM TRAUMA

Battering Animals in a Drum: How it Started

A method of inducing experimental traumatic shock by battering the entire, unanesthetized animal was introduced by
R.L. Noble and J.B. Collip in 1942, They invented a metal revolving drum, 15 inches in diameter. Two triangular projections, two inches high, are attached within. One of these carries a rat or guinea pig up the side during a turn, allowing it to fall when it reaches the top and to be picked up by the following projection. To prevent an attempt by the animal to break its fall, the paws are taped together. The drum is revolved by a motor 40 times, more or less, a minute. An animal is subjected to two falls for each revolution of the drum, a standard initial 'drumming' consisting of 360 revolutions, or 720 falls in nine minutes. The following are typical injuries from the battering in the drum: teeth broken or knocked out; bruising of head, paws and scrotum; hemorrhages into muscles; bruising of liver; engorgement of bowels, kidneys, lungs and intestines, with later appearance of ulcers in stomach and intestines. (Bayly, M.,1952).

Since 1942, this method of traumatizing conscious animals, chiefly rats, has been steadily used in the U.S. One investigator, B.W. Zweifach, began experiments with the drum at New York University in 1943, and has carried them on into the 1970's. He has had the help of several hundred thousand dollars of National Institutes of Health grants - out of the taxpayer's pocket, of course.

Aside from humane groups which have continually protested against experiments which result in such extreme and prolonged suffering in unanesthetized subjects, there have also been objections from scientists themselves. As long ago as 1949, six distinguished British scientists wrote to the conservative medical journal, The Lancet, asking "What amount of suffering is legitimate to inflict in the course of experiments on animals?" and ended with an appeal to other scientists to condemn such devices as the Noble-Collip drum as "shocking to a normal human conscience." In a definitive survey of experimental shock which was extensively published in Federation Proceedings and included a paper by Dr. Zweifach himself, H.B. Stoner contributed a major review, "Traumatic Shock Models." He flatly stated that the Noble-Collip drum had outlived its usefulness. "It is impossible to describe the extent of the injury and study the injured tissue quantitatively .... The method seems altogether too crude for modern purposes." (Stoner,1961).

Still Battering in the 1970's

What was too crude by 1961 was nevertheless quite acceptable to New York University School of Medicine in 1970, where Z. Hruza and B.W. Zweifach, supported by the ever-helpful U.S. Public Health Service (National Heart and Lung Institute), reported further work with the Noble-Collip drum. One table shows that 75 rats were battered until they died, some having received adrenalin-type drugs and some none, but all, unanesthetized, having been subjected to anywhere from 3,000 to nearly 5,000 falls. Since it has been found that some animals, though not, of course, escaping injury, can adapt better than others to the trauma and survive for varying periods, they can be used to test the effect of various drugs calculated either to increase or decrease their resistance to shock. Thus they are repeatedly returned to the drum for more "tumbling," and are then sometimes operated upon (now at last anesthetized) for examination of their organs. (Hruza, Z.,1970).

Anesthesia - To Use or Not to Use?

Noble and Collip originally introduced their drum with the idea that it would produce a pure kind of shock, uncomplicated by anesthesia (their animals received no pain-relieving drugs), hemorrhage (as used in another type of experiment to produce shock) or infection (as in endotoxin-stimulated shock). The omission of anesthetics has been continued by some experimenters UP to recent years; thus in 1976 V. Lockard and R. Kennedy at the University of Mississippi Medical Center were still battering unanesthetized rabbits 400 times at 30 r.p.m. in a NobleCollip drum. (Lockard, V., 1976).

On the other hand, perhaps because of some sensitivity to the growing public outrage over such experiments, "light anesthesia" has made its appearance. At Albany Medical College, New York, two groups, using rats in the drum, employed respectively "light ether anesthesia" (Sarfeh, I., 1977) and intraperitoneal sodium pentobarbital in a dose of 2 mg/100 g. body weight - also "light," since the normal dose is 3.5 mg. (Kaplan, J., 1976). At Downstate Medical Center, Brooklyn, New York, B.M. Altura, battering rats at up to 800 revolutions in the drum, used pentobarbital, 3 mg/100 g. body weight; this is as "light" as the above because it was given intramuscularly, for which the normal anesthetic dose would be higher than 3.5 mg. (Altura, B., 1976).

Briefly, the post-trauma effects under investigation in the above experiments were as follows: reduced antibacterial function of the phagocytes ("scavenger cells"): Lockard, Altura, Kaplan; functional abnormalities of the liver: Sarfeh; greater resistance to lethal trauma of female rats compared to males: Altura.

The fact that some anesthesia is being given (although probably not enough to eliminate all pain) shows that the investigators now discount such drugs as contaminants of their battering. If they are not contaminants then thousands of animals who have been denied pain-relieving drugs during the forty years that this crude Noble-Collip instrument has been in use have suffered to no purpose. What kind of "science" is this? Furthermore, the animals still suffer severely after the effects of the anesthesia wear off because, in no case, are postoperative analgesics administered. However, as was pointed out in the discussion of post-burn analgesia on p. 155, the effect of all these pain-relieving drugs could have been assessed long ago by running a control series of animals which had received the anesthetic and analgesic, or tranquilizer, but had not been battered in the drum. once these effects, if any, were known, the assessment of whatever other reactions were under scrutiny could have proceeded unhindered, and the animals could have been protected from pain until they were euthanized.


Alternatives

As long as the accident wards of hospitals are full of automobile crash victims, surgeons have a wealth of material to study. It is inconceivable that they need any scraps of information which may be picked up from the hit- or-miss battering of rodents in the Noble-Collip drum.


3. IRRITANTS OF THE DIGESTIVE TRACT

Mucosal Irritation and corrosion

A child who innocently swallows a highly corrosive substance like lye, or a strong acid, or an adult who does the same by accident or with suicidal intent, create a catastrophe for themselves and a very difficult problem for the surgeons who must treat them. The mouth, the throat, the esophagus, the stomach and the upper intestines are in the direct line of March of these irritants, which can produce ulcers, perforations, disabling strictures and sometimes death. Strong alkalis are most damaging to the esophagus and strong acids to the stomach and duodenum.

Against the background of these grim facts, household products containing lye or acids, and similar substances as defined by the Federal Hazardous Substances Act, are tested by their manufacturers on animals. This is done so that their toxicity can be defined preparatory to their being properly labeled, packaged and sold to the public. Also, the manufacturers are careful to protect themselves by extensive testing against potential lawsuits charging negligence brought by those injured by or claiming to be injured by the products. The government body which administers this act is the U,S. Consumer Product Safety Commission, and the Commission itself may test these substances.

The animals into whose mouths, esophaguses and stomachs the toxic substances are poured include rats, rabbits, cats, dogs and swine among others. The most devastating of these procedures is the test for corrosion of the esophagus, and in an authoritative publication of the National Academy of Sciences, Principles and Procedures for Evaluating the Toxicity of Household Substances, the following suggestion is made:

"The need for a special test for esophageal corrosivity has been questioned on the grounds that the customary battery of acute tests for oral toxicity, skin irritation, and eye irritation, when combined with information on chemical and physical properties, can provide reasonable presumptive evidence of a severe irritant or corrosive hazard on ingestion in the absence of empirical data. Indeed, the need for such an animal test might also be questioned on humane grounds." (NRC,1977, p.55).

This is a step in the right direction inasmuch as "humane grounds" are invoked, as a reason for questioning the use of esophageal testing, by a writer for the research "establishment," which rarely concerns itself with the subject of humaneness. But the battery of acute tests mentioned as substitutes are far from humane.

A
more acceptable alternative sparing the intact animal is needed.

Alternatives in Acute Testing of Irritants

The mucous-secreting epithelial cells of the mouth are of some value here: they can be easily removed by gently scraping the lining of the cheek, and in the laboratory their response to irritant or corrosive substances can be observed through the microscope. (Smyth, D.,1978, p.135).

If the effects of deeper penetration into the wall of the digestive tract need to be observed, it is possible to remove, safely, through a biopsy tube, full-thickness mucosal samples from the wall of the stomach or intestines. This can be done in humans as well as animals. The specimens can be cultured in a nutrient medium (Trowells T-8), with added antibiotics, for from 12 to 48 hours.1 Besides surviving longer than the isolated epithelial cells mentioned above (which live only a few hours), these small organ cultures contain many cells which preserve their usual anatomic relations and carry on metabolic activities including the synthesis of mucus and glycoprotein. (Trier, J., 1976).

It is true that these organ cultures have been developed to study normal gastrointestinal mucosal functions and intestinal diseases such as celiac sprue and ulcerative colitis, but, in principle, there is no reason why they cannot also be used in toxicological studies and in the testing of substances for irritancy and corrosiveness. of course the taking of biopsies requires some surgical skill and the organ culture procedure has to be technically precise. The in vitro approach also has certain obvious limitations: motility studies timing the movement of the poison through the alimentary canal cannot be performed, nor chronic studies. on the other hand, such processes as the synthesis of protein can be followed by adding a radioactive protein precursor such as (3H) leucine to the medium and observing either its incorporation into macromolecular tissue protein or the failure of synthesis owing to the toxic insult. Finally, many specimens can be removed during a non-recovery operation on an anesthetized animal.

Chronic Effects of Irritation and Corrosion

I have been discussing acute tests for irritants and possible alternatives. However, a far graver problem arises in seeking alternatives to experiments on the chronic effects of irritation or corrosion. In a typical procedure, animals are forced to swallow known corrosives. Surgeons then study the injuries that develop and test therapeutic measures either through drugs or surgery. observation of the unfortunate animals may last for months. Experiments on animals related to conditions which arouse maximum human concern - in this case, severe internal injuries following the swallowing of caustic substances by children and others - are often passed over in silence by those who under less affecting circumstances would be very vocal about the plight of the animals. However, since this book is focused primarily on the pain of animals under experiment, procedures of the kind about to be described cannot be overlooked, no matter how great their value to humans, if only because of the atrocious suffering which animals subjected to them undergo.

A group of surgeons at the University of Arizona College of Medicine opened the esophagus in 139 "mongrel dogs" under anesthesia, instilled lye into a 5 cm. segment of it which was tied off during the 60 seconds the caustic remained within, then flushed it out with water. This produced a burn extending through the full thickness of the esophagus in 77 dogs who survived for at least two weeks. Twelve dogs died with perforation of the esophagus in less than two weeks; the rest had less than full-thickness burns and were not included in the experiment since their injuries were judged not likely to develop into stricture of the organ, the object of the study.

The dogs with full-thickness burns were divided into groups of 24, 26 and 27 dogs respectively. The first group received no treatment; the second received injections of a steroid with the property of reducing inflammation and scar formation. These latter had their gullets dilated twice a week by a mercuryfilled "bougie." The third group were not dilated but were treated with a drug known as a lathyrogen which has the effect of producing a less rigid, more plastic kind of scar tissue.

Seventeen of the 24 dogs who received no treatment developed severe anatomical stricture of the esophagus, leaving an opening with a minimum diameter of half a centimeter or less. only four of the second group (steroid plus bougienage) and two of the third (lathyrogen) developed stricture, but these two groups tended to have persistent - and presumably painful - ulceration, apparently related to the mechanical abrasion from repeated dilatation and, somewhat inexplicably, to the effect of the lathyrogen. The first group, who were untreated, healed more quickly and escaped the persistent ulceration.

The animals were allowed to survive a total of 12 weeks from the operation until death, "unless they lost 15% of body weight and were obviously starving" (presumably because food could not pass the stricture).

The surgeons learned that the stricture caused by lye resulted from contraction of the full-thickness wound, not from the proliferation of bulky scar tissue, as had been previously thought. Also, they found that the effectiveness of the lathyrogen in preventing esophageal stricture is as great as that of "conventional" therapy (steroid plus bougienage), "with the distinct advantage that the hazards and difficulties of bougienage" - described as "unpleasant and often unsatisfactory" "are obviated." (Butler, C., 1977).

Postoperative Analgesia Withheld

Although the lye was instilled into the esophagus under anesthesia, there was no comment about postoperative pain relief; only a reference to an earlier paper. Nothing, however, was mentioned there, but again there was a reference to a still earlier paper for a description of the procedure. This "buck-passing" illustrates a recurrent problem facing anyone trying to discover whether analgesics routinely available to humans afflicted with extremely painful conditions were given, as they should have been, to animal subjects. Unhappily, the final answer, in a 1973 paper, proved to be "no": after the burn the dogs "were fed a soft-solid diet for four weeks and had no other treatment." (Madden, J., 1973).


Alternatives to Chronic Experiments

It is frankly not easy to find alternatives to these animal investigations of chronic surgical conditions, yet the suffering connected with the above experiments, and with burn experiments, seems most urgently to demand it.

Lacking suggestions for totally satisfactory substitutes, a piecemeal approach may be the best that can be offered at present.

1. The focus of investigation should be on the human victims of these accidents. Is this research developed and financially supported as much as possible?

2. When deaths occur, much may be learned from human autopsies. It was found experimentally that the lye stricture was caused by contraction of the full-thickness wound, rather than by pressure of scar tissue. Could this not have been deduced from macroscopic and microscopic examination of autopsy material?

3. If animals continue to be used, more attention to postoperative pain relief is imperative.


4. SURGICAL EXPERIMENTS CRITICIZED

Self-criticism in the Research Community

Animal surgery in America, and especially the lack of postoperative care, has its critics, even though the surgeon is a generally respected figure - but one who seems to flash like a meteor through the hospital on his way to and from important work in the operating theatre. No doubt he follows up on his own human cases with meticulous care, but, because of lack of time, any animals which he has been experimenting on are not likely to see much of him after the actual operative procedures. He assumes that the laboratory technician will take care of them. Inadequacies which may result have been testified to by two veterinarians who have been in a position to know what can happen on the inside. Dr. Joseph E. Pierce, D.V.M., of the National Institutes of Health, has pointed out:

"Cruelty to laboratory animals can be represented by the misuse of animals in experimentation. Here are some examples that now exist: ... the use of unhealthy animals in experiments; ... failure to have qualified technicians and professional assistance; the production of misleading information from misuse; failing to accomplish experiments with the minimum number of animals required; inadequate postoperative treatment."

He goes on to elaborate the last point.

"How many of us have studied animals that were several days postoperative without a body temperature recording or at least a stethescopic examination? How many of us have used the presence of a heart beat or the animal's ability to wag its tail as an indication of recovery?...How many animals are hyperthermic from infection, or dehydrated from diarrhea, or anemic from parasitism while involved in study?"

These findings, he says, can result in the publication of inadequate data. He might have added that they lead to similar experiments being repeated in order to correct the mistakes of the original ones. (Schwindaman, D.,1973, p.1279).

An even stronger statement comes from T.W. Penfold, D.V.M., for 25 years Director of the Animal Care Facilities at the University of Washington. Dr. Penfold felt so keenly about the inadequacies of technique in his own institution that he wrote to the municipality objecting to a proposal to make animals from pounds available to research institutions. He says:

"It has been brought to my attention that the City Council is reviewing the possibility to issue dogs from your city animal control center to federally licensed vendors for resale to institutions for research. My experience as a veterinarian with 25 years experience as the Director of Animal Care Facilities at the University of Washington enables me to be in a position of critical judgment in this matter. During my tenure in this position some 30,000 dogs have passed through, used both in acute and chronic research purposes, and much worthwhile information and life-saving techniques have been developed .... However, all this as it may be, to release animals to vendors to sell to research institutions for research is extremely inhumane ....

It is the common practice of research institutions to accept a dog or cat as a healthy animal providing that animal can stand and eat. Generally no preoperative procedures are performed as in human medicine .... Postoperative care is lacking in most institutions. These animals are usually left alone to roll around in cages during the recovery stage, more often than not are not given supportive fluid therapy, and follow-up of the postoperative care by the surgeon is, in general, lacking....

Not until institutions develop the necessary guidelines in establishing presurgery evaluation for candidates for chronic surgery, and a level of postoperative care that meets the evaluation as set forth by the School of Veterinary Medicine at Pullman or the Small Animal Hospital Association, and each institution has a veterinarian to oversee such policies, should any animal be released." (Penfold, T., 1974).

"Allowed to Die"

An experience at Berg Institute, New York University, in 1973, has made Dr. Penfold's comments painfully vivid to me. With another physician, I made an unannounced and unsupervised visit to the animal quarters there at about 10:00 p.m. on a Friday evening. We noticed a cage where a small, brown and white female dog, with a gaping, undressed throat wound which ran from ear to ear, was lying in a pool of blood. She appeared to be dying. We looked in vain for an attendant to notify. Finally, we telephoned the surgeon whose name was on the cage at his home in the suburbs and told him about the dog's condition. He said he had performed an experiment on the heart vessels (an anastomosis) which "had not been successful," and that the dog should be "allowed to die." He had no suggestions for terminal care or euthanasia.2

Although it is obvious that the dog was not being treated in accordance with the "professionally acceptable standards" required by the Animal Welfare Act, it may be unfair to condemn the Department of Surgery at Berg Institute on the basis of this one case. But what was objectionable was the obvious lack of concern.

Dr. William A. Nolen, a distinguished surgeon and author of the book The Making of a Surgeon, (Nolen,W.,1970), makes a pertinent comment:

"There are some professors of surgery who claim you can train a man to be a surgeon by letting him operate on dogs. I don't believe these professors. Dogs aren't people, and no matter how humane he is, a surgeon doesn't operate on a dog with the concern he shows for a human patient." (ibid., p.159).

Nolen concedes that it is possible to learn a particular technique by operating on an animal, and by a coincidence cites the same operation -anastomosis of the aorta - which had been performed so unsuccessfully at Berg Institute. This was a comparatively rare procedure at Triboro Hospital, where Nolen was assistant resident, but the chief surgical resident decided to carry it out although he had never seen one done. He practiced on twelve dogs, each of them obtained from a pound in Queens,3 with Nolen reluctantly standing by. The dogs were all humanely euthanized with an overdose of anesthetic after the operation, but Nolen says the experience forever cured him of any desire for a research career in a dog laboratory.

"Whack Them Hard"

Another surgeon, Yale graduate Elizabeth Morgan, discovered that she did not like animal research after nine months' exposure to it as a medical student. In her book, The Making of a Woman Surgeon, she describes her assignment to a laboratory at Oxford University. She worked there for a specialist in infectious diseases. Her project was to study the white blood cells of rats and mice who had been infected with the parasite causing trichinosis and with pneumonia bacteria. The nearly moribund animals were killed and put through a meat grinder so that the proliferating infectious organisms could be recovered.

Their standard method of killing the rodents, explained one of Morgan's coworkers, was either to chop their heads off, or to hold them by the tail and whack them hard against the edge of the counter. Unfortunately the rats were so inbred their tails tended to come off before "you could crack the head against the tabletop."

Morgan hated watching the animals sicken, and although she resorted to ether to finish them off, she also hated to kill them. She says that luckily President Nixon began cutting research grants, and by the time she returned to America most chiefs of surgery had found that trainees could get along without experimental animal research during their residency. (Morgan, E.,1980, p.100-104).

"Publish or Perish"

Thus there are many aspects of surgical research which justly arouse the humanitarian's ire. To recapitulate: the experimental animal may be sick to begin with; it may suffer unduly because anesthesia is withheld ("would defeat the purpose of the experiment"), or is inadequate, or is masked by curariform drugs; postoperative pain relief may be omitted, and other postoperative care may be so negligent as to add to the suffering; the animal may be subjected to multiple procedures; and, throughout, may be treated with a lack of concern which compounds its distress and fear (particularly if it is a former pet rather than a laboratory-bred animal). Finally, it may be killed inhumanely.

Many of the above deficiencies will introduce variables into the experiment and may account for the frequency with which the same procedures in the hands of two groups of investigators are often at odds. To sort this out more experiments have to be done and more animals sacrificed.

Worse than practice surgery (which may bring some improvement in technique) or "basic research" (with luck, some practical application may emerge), is research which is done merely to make a splash in a journal or to gain position and prestige in a research-oriented hospital center. Dr. Nolen, describing a young surgeon, "Al," who was doing research for just those reasons, maintains that "unfortunately, for every single dedicated, capable research surgeon there are dozens like Al. They clutter up the literature, burn up government and foundation funds that could be spent for a better purpose and waste their own talents, energy and time." (Nolen,W.,1970, p.14).

Reform is obviously needed but where will it originate? Governmental regulation has proved ineffective, and editors of scientific journals rarely refrain from publishing research, however superfluous, if among the co-authors is one with a prestigious name. Perhaps a judicious redistribution of grants, stimulated by citizen action and political pressure, is a possibility. And it would help if the American College of Surgeons or similar professional body were to emulate the position taken by their British colleagues in the Royal College of Surgeons. As described by Professor D.E.M. Taylor, representing the Royal College at a symposium of scientists and animal welfare workers where "The Welfare of Laboratory Animals" was the subject:

"The College is actively encouraging the development of alternative methods of investigation, such as tissue culture, in vitro modelling, clinical assay procedure and computer simulation and recommended that 'before embarking on a project entailing the use of animals, a research worker should satisfy himself that no alternative technique will meet the needs of his investigation.' However, there are still areas where there is as yet no reliable alternative to animal experimentation if the art and science of surgery is to continue to advance; these include the production of antisera, the assessment of toxicity and teratogenicity of new implant materials and much work in surgical physiology. We are all agreed that where animal experimentation is essential the standard of care and attention to our animals while they are in our charge should be based on the criteria that we would consider necessary for our patients. This regard for experimental animals is reinforced by a knowledge that unless the highest standards of care are exercised the results of the investigation may be invalid." (Taylor, D.,1977, p.103).


NOTES

1. Or much longer according to B.F. Trump et al. at the Carcinogenesis Program, Given Institute, Aspen, Colorado, 1977. They reported that human esophagus, colon and other explants can now 11 all be cultured for weeks to months with maintenance of normalappearing epithelium." (Harriss,C.,1978).
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2. We made our own arrangements for immediate euthanizing of the animal through an outside source.
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3. This was in 1958 when New York pounds were obligated to supply animals on demand to research institutions. Since the repeal of the Metcalf-Hatch Act in 1979, it is no longer mandatory.
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