How It All Began
The Origins of Animal Experimentation in the West
The idea of the good of humanity was simply out of the question, and would be laughed at, the great aim being to keep up with, or get ahead of, one's contemporaries in science.
--Dr. George Hoggan, former student of Dr. Claude
Bernard in the Morning Post , February 2, 1875
A certain logic does suggest using animals for human medical research. As mammals, humans have four limbs, just like mice, just like dogs, just like apes. As mammals, we do not lay eggs. Nor do mice. Nor do dogs. Nor do apes. They have four-chambered hearts, livers, lungs, and so on. So do we. It is not incredible that we should conjecture based on these apparent similarities. Granted.
Conjecture is one matter, but scientific conclusion is another. Throughout history, and still, scientists have stated as absolute a theory learned from animals, only to have the ensuing human data refute it. Our boxloads of data illustrate that using animals for human medical research is grossly unscientific, beyond any doubt. Mere experimentation on animals is not scientific; anyone can do that. If the results are inapplicable, misleading, and dangerous, then the fundamental principles supporting respectable knowledge-gathering crumble.
So, how did this puppy dog's tail-type science become so entrenched? Here, tracing back, readers will find that the history of animal experimentation is one of ignorance, immense egos, Church-determined biases, and bad news for animals and humans alike.
Methods for acquiring medical knowledge commenced soundly enough. In the fourth century B.C.E., Hippocrates fathered the concept of clinical research. This august scholar taught that, by observing enough cases, physicians can predict the course of a disease, both in terms of its likely effect and vulnerable population. Hippocrates' methodology has stood the test of time. Clinical observation still provides our most accurate and usable medical information.
Then, in second century Rome, a still revered physician put Hippocrates' human-based medical research process substantially off course. An experimenter of great energy and resources, Galen, was physician to the gladiators and to Marcus Aurelius's son. Galen might have continued investigation of the human model, but this practice was stanched by moral opposition. There already existed a bishop of Rome and a state-supported Church protocol disallowing human autopsies. So, Galen cut into goats and pigs and monkeys purloined from North Africa's Barbary Coast instead.
Thus, Galen became the father of vivisection. ( Vivisection literally means the cutting up of the living, but it refers to experiments conducted on animals.) Galen combined physiologic data from animals with his personal observation of humans to forge broad theories of physiology. He was a persuasive lecturer and prolific writer. More than five hundred written tracts on medicine and other subjects contributed to his historic importance.
Unfortunately, many of his theories fell short of accuracy. Galen's essential theory was this: Four bodily humors--blood, phlegm, yellow and black bile--govern all variables of health and disease. Likewise he believed that the liver manufactured blood. Though recognizing that blood travels, Galen fell short of concluding that it circulated . He described the heart as a warming machine for two separate types of blood and was convinced that veins and arteries were not connected. In his version of our blood's passage, it moved through invisible pores in the heart's intervening septum to the heart's left side, drawn by arteries that expanded like a bellows to draw fluid into them. Thus, according to Galen, the blood collected pneuma , drawn in by the lungs flowing both backward and forward from the heart."
Galen also described blood vessels directly under the brain. This network of blood vessels is present in many of the animals Galen dissected, but is absent in humans. He attributed cancer to the invasion of humors that resulted in inflammation.
To be fair, his was an era with little instrumentation and poor research conditions. That Galen erred is not surprising. Nevertheless, it must be said that medical knowledge in Asia was not likewise obfuscated, possibly because no Roman Catholic Church prohibited autopsy there. Nei Sing , the book that provides the basis for Chinese medicine, compiled nearly three thousand years before Galen, described the blood flowing from the heart in a continuous circle. Human autopsy rather than animal dissection would have eliminated (and eventually did eliminate) this and many other of Galen's inaccuracies.
Even with evidence that Galen's shortcomings were largely due to animal experimentation, his contributions through vivisection are still considered sacrosanct. Animal experimentation fans often cite them. In the early 1990s, the American Medical Association (AMA) published a "White Paper," promoted as a history of animal experimentation's contributions. (Chapter 5 explains AMA motivations for this.) The publication is a feat of omission and distortion, as is apparent by its citations in this book, of which the following is the first: "... the Roman physician Galen used apes and pigs to prove his theory that veins carry blood rather than air." As surgeon to the gladiators, certainly Galen's observations of humans were adequate to this conclusion. He did not require animals. Focusing exclusively on Galen's conclusion that blood travels around the body via vessels, the AMA and the animal experimentation contingency conveniently fail to mention the scope of Galen's errors and how they cast a shroud over medical progress, a darkness which did not lift for a millennium and a half.
Galen's errors, knitted together with the Church's prohibitions, suffocated medicine for centuries, both in terms of achievement and practice. Physicians adopted his frequently-amiss conclusions about the human body. The acceptance of Galen's doctrines, without equivocation, stymied the knowledge base about the human body and disease for 1,500 years. Doctors administered to the sick with treatments governed by Galen's four-humor theory--bloodletting and so forth--and tens of thousands of people died in the process.
The Church's influence over science in the pre-Renaissance era cannot be overemphasized:
Negative attitudes toward dissection of the human body; the stranglehold of Galen, whose four humors, doctrines of qualities, and inaccurate anatomy virtually paralyzed progress in medical science for fourteen centuries ...
Since Church edict forbade autopsies in medieval Europe, animal dissection revealed bones, tendons, ligaments and other fundamentals about mammals, including humans. Tendons connect the muscle to the bone and ligaments connect bones to each other. Since the baseline of knowledge was low, the addition of such knowledge was obviously good. Autopsies would have elucidated the same information and more, but it did not. Moreover, there were massive downsides to obtaining knowledge from animal experiments. Only with the study of the human body, centuries later, were faulty information and medical practices corrected:
[Galen] unhesitatingly transferred [extrapolated] his discoveries directly to humans, thus initiating many errors. The combination of Galen's immense authority and the prohibition by the Church of postmortem dissections of the human body conserved these errors well into the sixteenth century.
Formalized human dissection did not recommence for more than a millennium after Galen. Disquietude over what appeared to be errors in Galen's thinking nevertheless grew.
A Great Awakening, Renaissance Science
Finally, in the thirteenth century, Mondino de'Luzzi published what is believed to be the first text of human anatomy based on human dissection. But resistance was intense. Soon after, Paracelsus, a scientist who taught at the University of Basel, was dismissed for publicly burning Galen's work. Not until the Enlightenment, could humanity throw off its Church-bound ignorance and pursue the scientific method. We now know that Leonardo da Vinci actually discovered and documented arteries and arterial valves, but at the time his anatomical drawings did not receive sufficient attention.
Not until Andreas Vesalius was impetus sufficient to dislodge medieval thinking. In 1543, Vesalius, a Belgian anatomist and physician, began to dissect the human body and found, disturbingly enough, that most of what Galen had written was in fact erroneous. Not yet thirty, he published his results in De Corporis Humani Fabrica or Structure of the Human Body . Vesalius's book was published in the same year that Copernicus published his own startling and radical discoveries. Challenging the very foundations of civilization, those prescribed by the Catholic Church, these two books marked the beginning of the scientific revolution. But it was a troubled beginning.
Like d'Luzzi's text, Vesalius's actually represented human anatomy. All previously recognized publications were sheer speculation based on animal dissection. A pupil of the great artist Titian illustrated Vesalius's book. The written descriptions combined with the drawings proved to be truly paradigm shattering. One of Vesalius's more heretical findings was that both men and women had twelve ribs. This discovery shattered Church doctrine based on Genesis , that men had one less rib since Eve derived from Adam's rib.
Church officials were infuriated. Galen's theories were edict and his many loyal supporters tried to prove the upstart Vesalius wrong. The Church accused Vesalius of heresy, a capital crime. Young Vesalius was forced to hide from his colleagues and the authorities of the Church, in fear for his life. Heated dispute ensued, and fortunately, truth eventually won out. Vesalius eventually became physician to Charles V, the Holy Roman Emperor.
Once the scientific community overpowered the Church's objections, the acquisition of medical knowledge accelerated. From Vesalius on, anatomy based on human dissection was the norm during the Renaissance. Where Vesalius left off, Gabriel Fallopius continued. Using human dissection, Fallopius described numerous structures including the fallopian tubes, the inner-ear anatomy, and the clitoris.
Evidently, human autopsy provided better results than animal dissection. Galen's results were wrong because his methodology was wrong. This may seem obvious in retrospect, but at the time autopsy was very controversial. Human autopsy soon established itself as the method of choice for advancing knowledge at Europe's premier learning institutions. The systematic study of the human body via dissection began at the medical school in Bologna, which quickly distinguished itself as the premiere medical teaching facility. Other schools, like that at Salerno, previously the foremost medical school in Europe, faded into the secondary tier because their students were not so well versed in anatomy. Henceforward, universities changed their curricula to include human dissection. Pressure and competition between academics was such that the Church was forced to give way to modern advances, just as it had in other sciences after Galileo and Copernicus.
It was an exhilarating time with an open exchange of ideas over a growing body of knowledge. New information about "how humans work," all drawn from humans , cast aside Galen's stunting inaccuracies. It was, in every way, a renaissance . Eager students from elsewhere in Europe made their way to Italy to profit from this invigorating atmosphere.
One of these students at last expunged Galen's misinterpretation of blood circulation. As explained, the Chinese understood blood's action as early as 2,650 B.C.E. Although it may have been apparent to other experimenters previously, William Harvey is the Westerner now credited with the first accurate written description of the blood's circulation. An English physician who trained in the rigorous academic environment at Padua, Harvey observed the association of the heartbeat and pulse in human beings. His autopsies proved that blood circulated from the right heart through the lungs back to the left heart and into the arteries and veins, about which he wrote in 1628. This certainly debunked Galen's "invisible pores in the heart." Harvey even hypothesized the capillaries. Again citing the AMA's White Paper, pro-vivisectionists would have us believe that "Advances in knowledge made through these [animal] experiments included Harvey's demonstration of the circulation of blood in 1622."
Searching the literature of the time, however, we found an opposing description of Harvey's methods. Dr. Lawson Tait, one of the most famous surgeons of the nineteenth century, thought of it differently:
That he [Harvey] made any contribution to the facts of the [blood circulation] case by vivisection is conclusively disproved ... It is, moreover, perfectly clear that were it incumbent on anyone to prove the circulation of the blood as a new theme, it could not be done by any vivisectional process but could, at once, be satisfactorily established by a dead body and an injecting syringe.
Harvey trained with an Italian physician named Hieronymus Fabricius of Aquapendente. Fabricius, by performing autopsies, had discovered that valves prevent blood from flowing away from the heart in veins. Fabricius then postulated that blood goes from the heart in arteries and returns via veins. Early on, Harvey actually placed a tourniquet around his own arm to establish on which side blood accumulated, and also injected water into a corpse's heart, forcing it from one side to another. The Church still censored human experimentation at the time. Publicly, Harvey claimed that the conclusions came from dissecting eighty different animals because he did not want to admit breaking an English law against experimentation on human corpses.
Hence autopsies at last explained what we today consider a very basic phenomenon: Blood passes through the lungs to pick up oxygen. But regardless of how and why Harvey arrived at his conclusions, the truth is that it was, and is, possible to demonstrate the circulation of blood without using animals. Whether or not Harvey used animals does not mean that they were necessary . Even a superficial dissection of the human circulatory system would reveal the basic concepts demonstrated by Harvey in his experiments. Morticians prove it every day as they embalm cadavers.
During this epoch, Giovanni Morgagni popularized the autopsy. This was, naturally, the ideal method for correlating physical abnormalities and diseases. Morgagni employed this method, with some success specifically related to heart, lung, and liver disease. His high position at the medical school in Padua influenced the next generation of great medical thinkers attending that institution. Morgagni is remembered for his seminal work in pathology.
Autopsies were to reveal most of the facts that we today consider obvious or take for granted about the human body. "For over a century, starting in the late 1700s, the autopsy occupied center stage in scientific medicine. Modern concepts of disease and health were developed from a rich harvest of observations collected from autopsies. Thousands of diseases were identified, treatments developed, and therapeutic misadventures corrected."
Soon after Morgagni, in the late-eighteenth century, Marie François Xavier Bichat postulated that cancer was an overgrowth of tissue instead of inflammation. It had taken sixteen centuries to reverse Galen's original concept of humor invasions. Bichat discovered that different organs have discrepant textures and are composed of different tissues. Postulating that specific diseases attack specific tissues, he advocated study of the function and constitution of normal and diseased tissues. These fields of observation are known as pathology and histology . This revolutionary thought was based on his autopsy experience. Ironically, even though Bichat himself was distrustful of the microscope, his findings pointed to the exigency for microscopic observation.
By the 1800s, the autopsy was thought indispensable to the practice and advancement of medicine.
What were the achievements that assured such an important place for the autopsy? Among them were thousands of diseases discovered and described, numerous classifications of lesions, countless associations between disease states and anatomic abnormalities, and innumerable ideas for medical and surgical treatment. A bare listing of these findings would comprise a virtual encyclopedia of medicine ... Virtually the whole of modern medical knowledge was created through the study of autopsies . (Emphasis added.)
Medical science seemed to be moving out from under Galen's shadow at last. Then, tragically, history repeated itself.
Removing Humans from Human Medical Research
In the mid-nineteenth century, a French physiologist emerged to disturb the steady growth of medical revelation. His name was Claude Bernard. Bernard had turned to medical school only after failing as a playwright. A mediocre student, he obtained a position in a physiology lab. In as outrageous an act of recidivism as has ever occurred in the history of medicine, Bernard reinstigated animal experimentation. His energies turned vivisection into first a vehicle of elitism, then inevitably into establishment. Bernard succeeded in persuading the scientific community that if any disease could not be reproduced on animals in the laboratory, it simply did not exist--despite accumulated clinical (human) data to the contrary. Quite suddenly, lab research on animals was all the rage. The scientific community came to feel its methods were erudite, and even preferable to observation of humans. And, with abundant animals, it also made doing science more convenient. How did this happen?
In 1865 Bernard published Introduction to the Study of Experimental Medicine . In it he described the laboratory as the "true sanctuary of medical science." He extolled laboratories, not bedsides, as offering the greatest insights into medicine and professed that lab animal experiments could do far more to heal sick patients than clinical observation:
I consider hospitals only as the entrance to scientific medicine; they are the first field of observation which a physician enters; but the true sanctuary of medical science is a laboratory; only there will he seek explanations of life in the normal and pathological states by means of experimental analysis. In leaving the hospital, a physician ... must go on into his laboratory; and there, by experiments on animals, he will account for what he has observed in his patients, whether about the actions of drugs or about the origin of morbid lesions in organs and tissues. There, in a word, he will achieve true medical science ... Experiments on animals, with deleterious substances or in harmful circumstances, are very useful and entirely conclusive for the toxicity and hygiene of man. Investigations of medicinal or of toxic substances also are wholly applicable to man from the therapeutic point of view; for as I have shown, the effects of these substances are the same on man as on animals, save for difference in degree. (Emphasis added.)
He and his colleagues also explained why the animal experimenter is above compassion, in tones not unlike H. G. Wells's megalomaniacal Doctor Moreau,
The physiologist is not an ordinary man: He is a scientist, possessed and absorbed by the scientific idea he pursues. He does not hear the cries of animals, he does not see their flowing blood, he sees nothing but his idea, and is aware of nothing but an organism that conceals from him the problem he is seeking to solve.
A pupil of Bernard's, Elie de Cyon, echoed his mentor's sentiment,
The true vivisector must approach a difficult vivisection with the same joyful excitement and the same delight wherewith a surgeon undertakes a difficult operation ... He who shrinks from cutting into a living animal ... will never become an artist in vivisection.
Not exactly attitudes that foster compassion. Not surprisingly, Bernard also thought experimentation on humans was not immoral. He occasionally performed his experiments at his home, even purloining the family pet. His wife and daughter were so appalled by his methods that they founded a humane society. They set up a home for stray dogs and scoured the streets, hoping to intercept lost dogs before Bernard did.
The female Bernards were not alone in their horror. One of Bernard's students, Dr. George Hoggan, was one of the founders of the first antivivisection society in England in 1875, the Victorian Street Society. He wrote,
We sacrificed daily from one to three dogs, besides rabbits and other animals, and after four years experience I am of the opinion that not one of these experiments on animals was justified or necessary. The idea of the good of humanity was simply out of the question, and would be laughed at, the great aim being to keep up with, or get ahead of, one's contemporaries in science even at the price of an incalculable amount of torture needlessly and iniquitously inflicted on the poor animals.
Recognizing that animal experimentation, though macabre and invalid, already had peer respect, Hoggan stated that no medical student or physician would dare challenge the vivisectors. They feared that they would be expelled from their profession and unable to earn a livelihood.
Hence, just as medicine was showing signs of recovering from deceptions sown by Galen's animal-based inaccuracies, Bernard snapped a lid on progress. Bernard and the socioeconomic conditions that proliferated because of the Industrial Revolution reinstated Galen's erroneous methods, and they still persist today.
To understand how animal experimentation again took hold, despite its many drawbacks, it is perhaps important to examine the philosophical mood of the times. Contrary to the open, expansionary sentiment of Renaissance Italy, a stricter and more conservative disposition permeated Europe and America during the Victorian age. Based on Bernard's precedent, would-be scientists understood that animal experimentation could provide both money and reputation. Those who lacked talent in a clinical setting could turn to lab investigations for income.
Philosophies surfaced to reinforce a logic for mining nonhumans for human insights. There were those who admitted animal experimentation did no good but pursued it because their preeminence as humans put them above the common laws of morality. Professor Leon Le Fort, head of the Faculté de Medicine in Paris explained thus,
Speaking for myself and my brethren of the faculté, I do not mean to say that we claim for that method of investigation [vivisection] that it has been of any practical utility to medical science, or that we expect it to be so. But it is necessary as a protest on behalf of the independence of science against interference by the clerics and moralists. When all the world has reached the high intellectual level of France, and no longer believes in God, the soul, moral responsibility, or in any nonsense of that kind, but makes practical utility the only rule of conduct, then, and not till then, can science afford to dispense with vivisection.
First published in 1859, Darwin's On the Origin of Species shook the world. It sparked vehement dissent from religious groups and from scientists who struggled to squash its revelations into an interpretation that validated their thinking. According to Darwin's actual theory of natural selection, humans are not the perfect culmination of God's work. There is no slow upward progression of species leading to Homo sapiens . Humans are not the paragon. Rather, evolution is about mutation and adaptation. Therefore, other species are equally ideal, equally successful other animals. It is plain now that Darwin's theory accounted for the failures of animal experimentation. That animals are not defective first drafts of humans makes them unlikely test beds for human medicine.
At the time, however, Darwin was widely misinterpreted. People grappled with his findings, trying to match them to prevailing sentiment and scientific activity. The Church, interpretations of the Bible, and indeed most humans clung doggedly to their anthropocentrism and the idea of our dominion over nature. High thinkers even went so far as to exume the works of French biologist Jean Baptiste Lamarck, ignored in his time nearly a century before, because they supplied a more pleasant interpretation of evolution.
Lamarck's less troubling philosophy arranged God's creatures hierarchically. He had written that evolution was like a tree, each branch more advanced than the one below it. Dogs, cats, goats, whales, apes, and so on--all were nature's failed attempts to produce man. Whereas Darwin proved that speciation is not a tree, but an intensely complicated bush that never ceases to grow, Lamarckism kept man at the pinnacle. For God-fearing scientists, Lamarck's theory was a lot more reassuring.
Bernard, for his part, rejected evolution altogether and remained a creationist. His experiments were predicated on the assumption that animals were below humans but similar enough to draw data from. He overlooked that nature fashioned each species differently. Not surprisingly, these differences account for many of the research failures covered in this book, all of which took place after Bernard.
Researchers continued to use animals in their attempts to get to the bottom of human physiology and disease. As the Industrial Revolution dawned, animal experimentation labs tooled up as its medical research manifestation.
Senselessly, human clinical observation took a back seat to lab work with animals. Since Bernard's time, patient observation has been considered strictly anecdotal until confirmed on animals in the lab. Recognize that the word "anecdotal" has a negative connotation among scientists. It refers to unusual occurrences, generally observed in a clinical setting and carefully described. Even today, applying the adjective "anecdotal" derogates observations that have not been repeated in a laboratory. From the outside, we can see how preposterous this is. We can agree that actual medical problems and effective therapies in humans are meaningful, whether or not they can be perpetrated on another batch of mammals.
Nevertheless, Bernard held that those seeking the cause of life or the essence of disease through humans were "pursuing a phantom." He said, "The words life, death, health, disease, have no objective reality." Rather startling didactic for a medical professional.
It is not disease that is the phantom. It is animal-model data in transit to human application. During this forced voyage from laboratory cage to Homo sapiens , the data dies. It loses its substance. Scientists grab at this specter trying to mine it for worth against cancer, against heart disease, against degenerative disease, against mental illness. Always it is elusive.
The Tenacious Mistake
No matter how elusive the comparison, no matter how unsound the practice, the phantoms of animal experimentation proliferated, seeping into every branch of medicine and haunting every human-based finding. Apparent progress based on animal experimentation reinforced the efficacy of the lab protocol, as it still does. That the progress later proved to be no progress at all did not however stem the trend. (This happens all the time today. When a therapy proves effective in mice, it is front page news. Television specials. Public radio interviews. When, a few months later, the therapy proves induplicable, it is a news footnote, an after-mention, unnoticed by the public at large.)
In the nineteenth century, respected scientists, chief among them Louis Pasteur and Robert Koch, lent credibility to the animal experimentation convention when their vivisection work resulted in ostensible discovery. In reality, animal experimentation actually misled their investigations, most notably in the field of virology, as Koch later emphasized.
Pasteur, who was actually a chemist and not a physician, made three great contributions to medicine--sterilization, pasteurization, and the germ theory of disease. None relied on animals.
Most people of the mid-nineteenth century believed that deadly diseases occurred as a result of spontaneous generation --that is, the diseases sprang from nowhere. Questioning why wine goes bad, Pasteur found that living organisms, yeasts, occupied the wine. The wine deteriorated if the yeast was not killed prior to storage. This discovery led to further study and the suggestion that humans were as susceptible as wine to tiny infectious organisms. Pasteur used his influence to convince physicians to sterilize their surgical instruments and work in a cleaner environment.
Based on observation and thought, not research on animals, Pasteur formed a fresh tenet to replace spontaneous generation, which he called the germ theory of disease . He postulated that disease was communicable because of small living organisms spread from person to person by contact. Today, we immediately accept this. But in Pasteur's epoch, the idea that tiny organisms could kill large mammals was incredible. Pasteur's substantial evidence and his own eloquence ultimately convinced his peers.
Many call the germ theory of disease the greatest single contribution to medicine ever. The importance of Pasteur's finding to our discussion is this: The germ theory forced people to recognize imperceptible influences, influences smaller than the gross similarities we share with animals. Recognition of this aspect is essential to understanding the inadequacies of animal experimentation.
There was an essential flaw in Pasteur's earliest assessments. He believed that all species could become ill from the same microbe. As we now know, and as Pasteur may have eventually deduced, those who do become ill do not necessarily become ill in the same way. Not yet realizing this, Pasteur used animals as pseudo-humans as he attempted to craft a rabies vaccine. He took spinal column tissue of infected dogs and made what he thought was a vaccine. Unfortunately, the vaccine did not work seamlessly and actually resulted in deaths. Yet, this gross failure somehow did not detract from reverence for the animal-lab process. In truth, the only successful animal experimentation Pasteur did was for the benefit of animals. He studied anthrax in ungulates and cholera in chickens and found vaccines to prevent them.
Robert Koch, another esteemed bacteriologist of the day, reinforced Pasteur's germ theory. Koch extolled six assumptions, which came to be known as "Koch's postulates." He stated that these six criteria must be met to implicate a specific pathogen as causing a particular disease:
· The organism must be present in every case of the disease.
· The organism should not be present in other diseases.
· The organism should be isolated from a sick individual.
· The organism should be purifiable.
· The organism should induce the same disease when inoculated into an animal.
· The animal should be able to pass on the organism to other animals via a culture medium.
Initially, Koch demonstrated his postulates by isolating Bacillus anthracis , the causative agent for anthrax, a fatal disease of cattle. This was the first isolation of bacteria ever. Koch isolated it in mice. When Pasteur went on to vaccinate sheep with a weakened form of the bacteria successfully, it did certainly suggest the efficacy of Koch's postulates. There, however, felicitous parallels ceased. Koch's own subsequent work ultimately proved that not only were animal experiments unnecessary, but that they could be quite misleading.
In the 1870s, Koch isolated Mycoplasma tuberculosis , the causative agent for tuberculosis, then a horrific scourge on the scale of cancer or AIDS today. He used samples from human tissue for tuberculosis and for cholera, to which he then turned his attention. Koch traveled to India in his capacity as the head of the German Cholera Commission. In 1884, he reported on the progress of experiments on fifty white mice,
Although these experiments were constantly repeated with material from fresh cholera cases, our mice remained healthy. We then made experiments on monkeys, cats, poultry, dogs and various other animals that we were able to get a hold of, but we never were able to arrive at anything in animals similar to the cholera process.
Eventually, Koch put away the mice and discovered the causative organism by using a microscope and examining material from human victims of the disease. He was also able, through epidemiological methods, to identify how the disease was transmitted in contaminated water, on eating utensils and so on. Ultimately, Koch concluded,
Should it prove possible later on to produce anything similar to cholera in animals, that would not, for me, prove anything more than the facts which we now have before us. Besides, we know of other diseases which cannot be transferred to animals, e.g., leprosy, and yet we must admit, from all we know of leprosy bacilli, that they are the cause of the disease ... We must be satisfied that we verify the constant presence of a particular kind of bacteria in the disease in question and the absence of the same bacteria in other diseases.
The same sort of realization, though even more of a jolt, issued from Koch's tuberculosis work. Attempting, over time, to develop a vaccine against tuberculosis based on animals, Koch had injected tubercle bacillus into frogs, turtles, mice, guinea pigs, and monkeys. The bacterium killed the frogs and turtles; however Koch was ultimately able to cultivate a vaccine from mice.
Hopeful tuberculosis sufferers flocked to Berlin to participate in Koch's new "cure." Disaster struck. The human trials of Koch's vaccine were ruinous because in humans the disease takes a different form. In fortunate patients, the mouse-modeled vaccine simply did not work. In other previously recovered patients, the vaccine caused the disease to flare up. Scientists acknowledged,
Tuberculosis in human beings and tuberculosis in animals are distinctly different , although caused by the same microorganism. The disease in animals is relatively simple in character, and fairly predictable in its course, whereas in the human being it is far more complex; so one must not assume that a drug that is effective in the laboratory animal will be equally effective in man. (Emphasis added.)
Clearly, two of Koch's postulates, the ones involving animals, were erroneous. Personally witnessing the amount of havoc they could produce, Koch retracted them. His experience proved that when a known disease-causing organism or pathogen, is injected into animals, the response it elicits depends on the species. Other deadly diseases in humans cause no illness whatsoever when injected into animals. Even then The Lancet published, "Thus we can not rely on Koch's postulates as a decisive test of a causal organism."
Not long before he passed away, Koch himself wrote: "An experiment on an animal gives no certain indication of the result of the same experiment on a human being." Despite Koch's recantation, scientists clung stubbornly to the animal model. Though Koch's two postulates regarding animals are inaccurate, and Koch himself disclaimed them , all six postulates are part of every high school biology curriculum and every modern student of bacteriology still memorizes them. Few medical students are advised of Dr. Koch's own disclaimers.
As indicated, animal experimentation played havoc with vaccine development. The animal-model protocol was also demonstrating its drawbacks in other areas of research. Nonetheless, proponents of animal experimentation regularly distort historical accounts of Pasteur and Koch's work to suggest that their discoveries did issue from the animal lab.
Despite what was fast becoming the "machine of animal experimentation," clinical observation and autopsies abided as the most important methods for true discovery. Not surprisingly, the great advances came about in spite of lab animals, not because of them. Whenever a discovery occurred, researchers dispatched to the lab to "validate" it. The animal assay became a sort of automatic response to any suggested medical achievement. If vivisectionists could not validate the achievement, then their so-called science invalidated the finding, clinical evidence to the contrary.
Examining the history of early endocrine investigation exposes the absurdity and danger of this animal experimentation part of the sequence. Physicians used to believe that the proper functioning of organs was entirely dependent on the nervous system. The discovery of the endocrine system proved that this was too simplistic. Our endocrine glands produce a variety of hormones. Hormones travel throughout the body like messengers, acting to regulate the functions of other organs. For instance, clinical observation led to the discovery that the pituitary gland was involved in abnormalities involving the sex glands.
The adrenal glands are located on top of the kidney. They are a component of the endocrine system. The adrenal glands secrete a number of hormones including steroids and adrenaline, also known as epinephrine . In 1855, Thomas Addison described five patients in whom tuberculosis had invaded and crippled the adrenal glands. After the human findings were known, researchers hastened to the lab to remove animals' adrenal glands. However, they were unable to reproduce the same symptoms. Unfortunately, this failure in what Bernard had called the "true sanctuary of science" stuck, effectively negating Addison's clinical observations. For thirty years, Addison's disease was ignored. Not until 1882, did James F. Goodhart associate adrenal atrophy with the symptoms Addison had described.
Since Addison was the first to describe its symptoms, Addison's disease now bears his name. We now know that Addison's disease occurs when human adrenal glands are not able to produce specific hormones required to regulate our electrolytes--potassium, sodium, and other similar elements. It is life threatening, causing vomiting, diarrhea, and ultimately death from heartbeat irregularities.
In 1893, a physician named George W. Oliver tested adrenal secretions on his son. He described a decreased diameter of the radial artery accompanied by increased blood pressure. As we know, adrenaline prepares us for "fight or flight." It increases blood pressure and decreases the lumen of arteries, thus diminishing the amount of blood going through them. This is why people with heart disease experience chest pain or angina if they are suddenly frightened. Take note: This was discovered in a human.
What do animal-experiment advocates remember? This: Oliver then went to physiologist Edward A. Shafer's lab and "validated" on dogs the results he had seen on his son. Although the role of the adrenal glands was based on clinical observation from start to finish, and although animals only reproduced data already known, many sources still credit Shafer's animal experiments with revealing the role of the adrenals. Once again animal experiments were counted more valuable than human observation.
The female reproductive organs, the ovaries, are also a part of the endocrine system. Dr. Robert T. Morris demonstrated ovarian function in a surgical procedure on women in 1895. A researcher named Emil Knauer reproduced the procedure in rabbits in 1896. Whom does history credit? Knauer, in yet another example of clinical observation and discovery falsely attributed to a lab-animal scientist.
The predilection for experimental zoology was so strong around the turn of the century that animal experimenters actually held more sway than physicians in the medical community. Not just these scientists, but many scientists of the epoch piggybacked on knowledge that had been documented in humans much earlier.
Gastric physiology, the study of digestion, is another case in point. As long ago as 1833, U.S. Army surgeon and physiologist William Beaumont had the good fortune to observe gastric activity inside a patient named Alexis St. Martin, the recipient of a shotgun blast to the abdomen. Most would have died as a result of this trauma, but St. Martin lived to the age of 82, with a large hole in his belly. Through this hole, Beaumont made detailed observations, describing gastric motility, gastric juice composition, and influences over the secretion of gastric juice in humans. Claude Bernard, upon hearing of this work, proceeded to "validate" it in animals.
Another of Beaumont's subjects, known as "Tom," had eaten some very hot food as a child and suffered from a very tight stricture in his esophagus. This too allowed Beaumont to observe numerous functions of the GI tract. Beaumont passed away in 1853.
Over fifty years later, Ivan Pavlov, the Russian physiologist, received the 1904 Nobel Prize following the publication of his articles about the enervation to the stomach and other mechanisms of gastric function. Pavlov observed animals' digestive systems, even though Beaumont had already observed and documented these revelations in humans many decades before.
Observations of Beaumont's subject, "Tom," eventually led A. J. Carlson to conceive of a new surgical procedure. By placing balloons into the esophagus of patients with strictures, he was able to dilate the esophagus, thus allowing the patient to swallow normally. This procedure is still performed today. Carlson first experimented on animals like most researchers of his day. But the experimentation could have been avoided without any risk to his patients, thanks to Beaumont's work. Animal experiments conducted since then have been entirely unnecessary since, unfortunately, accident victims like Tom and St. Martin abound.
While Pavlov was exacerbating his dogs' stomachs, a truly accurate description of gastric physiology issued from Walter Canon. In the early-twentieth century, Canon developed the technique of radiographing a patient after the patient had swallowed radio-opaque substances, thus outlining the esophagus and stomach. He described various physiologic changes in the GI tract based on this technique. Neither the development of this technique nor the experiments that followed necessitated animals. Canon did perform some experiments on animals but only to "validate" human data.
Window to the Microcosms
Even though animal experimentation presented a persistent impediment, medical progress pushed on, thanks to contributions like Canon's. The bulk of this technological ingenuity we cover in later chapters. It is important at this juncture, however, to discuss one critical leap toward our understanding of living systems, and that is the advent of the microscope. Magnification produced a medical revolution. The ability to see cells and even cell components rendered reliance on the animal model even more ridiculous. Finally, scientists could acquire hard data in regard to complicated human cell function and directly observe how it reacted to disease and therapies. We no longer had any reason at all for applying disease and therapies to nonhumans for purposes of divining human outcome.
Curved surfaces were recognized as having optical properties as long ago as 300 B.C.E. People had been examining items under actual magnifying lenses since the fourteenth century, with better resolution all the time. In the productive atmosphere of renaissance Italy, Marcello Malpighi, invented the first real microscope in 1650. And just a few years later, in 1665, the English scientist Robert Hooke published his Micrographia , the first textbook of microscopy. Based on his observations of cork, Hooke described dead cells. This was landmark work. Shortly thereafter, the Dutch scientist Anton van Leeuwenhoek published a paper, identifying living cells in detail. Without the aid of animal experiments, he described bacteria and spermatozoa.
After this first flush of discovery, progress slowed. Acceptance of a cell theory was delayed because researchers, in typical fashion, at once tried to identify cell components using animal tissue. They used chick embryo sac cells since these are translucent. (Until techniques for processing tissues for microscopic examination were developed, translucency was desirable.) These atypical cells do not have a cell wall or membrane, and the cells were therefore difficult to distinguish. Using human tissue from surgery and autopsy might have prevented these and other errors based on animal cells.
The watershed invention was the modern microscope, built by J. J. Lister, the son of the famous British physician, Baron Joseph Lister, in 1828. The younger Lister's invention of a true magnifying device led directly to the cell theory upon which modern biology and medicine is based. Finally, researchers were able to confirm the existence of cells because they could observe the cell walls of plants. Plants, not animals provided the material for the confirmation. Though Lamarck and others had written that life depended on cellular tissue, German botanist Matthias Schleiden and German zoologist Theodor Schwann formulated the cell theory with particular clarity in 1839. Seeing underlying structural similarities between plant and animal cells, they stated that all living organisms consist of cells and are capable of reproducing themselves. The obvious upshot of the cell theory is this: Whole organisms can be understood through the study of their cellular parts. This revelation is of tremendous importance to medical discovery, and also to our argument discrediting animal experimentation. It also bears repeating that the cell theory would very likely have been realized much earlier if investigators had used human tissue from autopsies.
More comprehensive evidence regarding cell composition and cell function followed. It was one hundred years after Bichat identified gross discrepancies between body tissues. A German pathologist, Rudolf Virchow, expanded on this idea in 1858, introducing his theory that all cells come from preexisting cells. In his description of leukemia, it became apparent that diseases occur on a cellular level. Thus, Virchow demonstrated that the cell theory applies to diseased tissue as well as to healthy tissue--that is, that diseased cells derive from the healthy cells of normal tissue. He concluded that only by studying tissue under the microscope could we correctly deduce our nature. Virchow's contributions ushered in modern medicine.
Virchow's ideas led directly to knowledge of cell division and cell differentiation. Peering into a microscope, scientists saw in broadening detail the many differences between human cells and the cells of other species. It was clear that though all cells--plant and animal--have characteristics in common, the cells of each species are distinct and they demonstrate different susceptibility to diseases. They are not identical when healthy. The diseases that assault them are not the same, and even when they are similar, they assault them differently. Sir William Osler, a physician and educator of tremendous influence who had studied under Virchow, carried the illuminations of human cell research forward toward the twentieth century.
One can understand how this knowledge undermined any apparent relevance of animal experimentation. Watching cells under a microscope, scientists implicitly grasped that medicine had advanced beyond drawing parallels between all creatures with four-chambered hearts. Now, they had evidence that not all four-chambered hearts are alike. They could clearly see that human heart tissue cells react differently to medications and diseases from cells of a pig's heart or a chimpanzee's heart.
In the late-nineteenth century, Hans Gram, Paul Ehrlich, and Robert Koch used tissue samples from humans to develop dyes and techniques for selectively staining cell parts. Employing the stains, scientists refined their detection of tiny cell structures and their diagnoses of diseases. Again using human tissue, Ehrlich discovered a new white blood cell, the mast cell, while using the new dyes. The mast cell is involved with allergic reactions. With increasing amplification, and more technology, scientists were to learn more and more about the ways we differ from animals and even each other.
Throughout history and today, please observe the same pattern: each new development brings better methods for more detailed observations. And with each method the merit of animal experimentation diminishes. With expanding medical ingenuity, similarities between humans and animals fade, becoming less significant, while remaining differences between humans and animals become even more important.
In other words, even on the gross level (the visible level) there are differences between species. On the cellular and molecular levels these differences are magnified exponentially. For example, there are few visible differences in the way blood gets around in mammals. Blood circulates in horses as it circulates in pigs as it circulates in humans. But for scientists hoping to elucidate something as precise as human coronary-artery disease, plumbing animals for knowledge is an exercise in frustration. Likewise, there is a vast difference in recognizing that the pancreas is involved in metabolism in all mammals and stating that pancreatic cancer in a mouse is the same as pancreatic cancer in a human. The comparisons just have not held up, as we describe throughout this book.
Millions of variables skew results even within the human species . Is the patient male or female? How old was the patient when afflicted? What sort of lifestyle supports or undermines the patient's health? Does the patient have any concurrent illnesses? Are other medications taken that impact the course of the disease? Does the illness run in the family? Some scientists have remarked that the only accurate model of your illness and its most effective therapy is you .
Most humans are sufficiently similar that if penicillin cures my skin infection, it will probably cure yours, too. Yet, there are exceptions even to this. What if your skin infection is due to a virus, whereas mine was bacterial or fungal or parasitic? What if you are allergic to penicillin? There are also differences in the disease itself as it manifests in different people.
Race and gender, too, influence susceptibility to disease and receptivity to therapies. Some races are more vulnerable than others to high-blood pressure. People with light-colored skin are more prone to certain types of skin cancer than people with dark skin. Men and women react differently to pain medications. Pain medications that work on kappa receptors (central nervous system tissue that helps fight pain) work better in women. Why? Researchers believe it is because testosterone, found in greater quantity in men, inhibits pain medications that act on kappa receptors. Women normally have lower hemoglobins, probably because of menstruation. This protects them from iron-induced myocardial damage, a predisposing factor for heart attack. Men and women have different reactions to selective serotonin re-uptake inhibitors, such as Prozac. Women are much more likely to experience sexual dysfunction than are men. Very few non-Jewish people suffer from Tay-Sach's disease. Sarcoidosis is much more prevalent in black people than white people. So is gastric cancer. Very few non-black people suffer from sickle cell anemia.
Differences such as these proliferate. The need to learn all these differences accounts, in large part, for the long duration of medical training. People are different from each other. If each person responds differently to illness and medication, imagine the variability of animals in regard to people. Multiply these complications by a million when you try to extrapolate information from one species to another.
Yet, people still believe that we should use animals as models, particularly primates, because of their genetic material's proximity to our own. This common argument in favor of vivisection is actually very flawed.
To explain, chromosomes bear the basic units of heredity, called genes . These genes are passed down from generation to generation, and they also govern day-to-day function of living and reproducing cells. The essential genetic material is DNA, or deoxyribonucleic acid. Eighty-four percent of the DNA in New World monkeys and humans is the same. Most scientists agree that between 97 and 99 percent of our DNA is the same as the great apes. This sounds good. But further inspection reveals the inadequacy of the argument.
What the animal experimenters fail to mention is twofold. First, remember how physicians used to believe that the nervous system alone governed the smooth functioning of our organs until they discovered the important and more complex role of the endocrine system? When there is a major leap in our understanding that reveals increased complexity of systems, it tends to diminish the role of simplistic former explanations.
We now know that proximity in DNA is (rely a small part of the picture, leaving unexplored the vast infinitesimal spectrum of base-pair sequences . The DNA of humans is composed of billions and billions of base pairs, about which we have known very little until recently. It is not the number of pairs in common that are important but rather the specific pairs and sequences of the ones that are not . The specific pairs and sequences are what makes you a human and Fido a dog. The base pairs tell the body to form amino acids, which are the building blocks of the body.
To give an idea of how complex this is, look at one important enzyme, cytochrome-C. It is composed of 104 amino acids in a very specific sequence. Monkeys have the same cytochrome-C sequence as humans except for one amino acid. There are twelve differences between humans and horses and 22 differences between humans and fish. The fact that only one amino acid is different in monkeys means that we are more similar to them than we are to fish. It does not negate the fact that monkeys are different from humans. It is very, very small changes like this in our DNA that separate the various animal species. Very small differences on the DNA level translate into very large differences between species and even within species. (For example, one change in the DNA base sequence at a particular gene results in sickle cell anemia. Just one change. The same is true for cystic fibrosis.)
Moreover, approximately 97 percent of our DNA is unaccounted for in terms of function. So, the DNA argument in favor of animal experimentation is highly misleading. It is like saying, "we are all alike except where we are different." It is these differences that make the results of the study of animals inapplicable to humans.
Animal experimentation overwhelms our view of tiny degrees such as base-pair sequences. Coming chapters disclose how often and at what cost it has persuaded researchers into circuitous and dangerous detours that seem never to lead to viable human application. We also explore the technology and alternative-research methods that have moved our knowledge along, in spite of using animal models.
Copyright © 2000 C. Ray Greek, MD, and Jean Swingle Greek, DVM. All rights reserved.