Crash course in medical history

Opponents of animal research often portray two of the pioneers of experimental physiology, François Magendie (1783-1855) and his student Claude Bernard (1813-1878), as deranged, vicious, and sadistic individuals who derived pleasure in harming animals. Moral philosophers Peter Singer and Lori Gruen convey this sort of message in their book “Animal Liberation: A graphic guide”.

Portrayal of Claude Bernard in Singer and Gruen's book

Portrayal of Claude Bernard in Singer and Gruen’s book

A quick look at how Claude Bernard’s face is portrayed in their book is sufficient to get a sense of Singer and Gruen’s feelings towards scientists who engage in animal research. The peculiar use of quotes around ‘experiment’ in the caption suggests they believe the work did not qualify as legitimate scientific research, nor that it could contribute any benefits to mankind. Such view fails to consider the historical context of their experiments.  In particular, one could ask how were human patients treated by their physicians of the time.

Here is a brief summary of 19th century medicine —

The theory of counter-irritation was in vogue. To counter-irritate basically meant causing additional wounds to the patient as a form of treatment. One technique involved inserting inflamed limbs were into giant anthills. More convenient was produce large blisters by means of a fire iron or acid. In 1824, an article in the Lancet by Dr. Abernathy suggested that a 1 foot square blister was probably a bit too large — several small blisters were indicated instead.  A third method of counter-irritation involved making a saw-shaped wound and inserting dried peas or beans into it. The doctor would then ensure the wound remained open, keeping it from healing, from weeks to months, replacing the peas and/or beans as necessary.

Leeches were used in vast quantities and for many purposes.  Physicians would lower leeches down patient’s throats.  Hundreds of them would be used to bleed a man’s testicle over days. Leeches were also applied to the vagina to relieve “sexual excitement” and, not to discard other orifices, doctors would push them up the anus. It was noted that during these procedures there was always a possibility that some of the leeches would get lost inside the patient body which, according to the physicians of the time, resulted in  “very annoying accidents”.

What about mental disease? A common treatment involved psychiatrists spinning patients in centrifuge-like machines a hundred of times per minute. This is how unruly patients came to understand the authority of the doctor, with one of them asserting that the more lively his intimidation towards the apparatus the more charitable the effects of the therapy.”  

rush

Benjamin Rush’s tranquilizer chair

Benjamin Rush, one of the founding fathers and signatories of the Declaration of Independence, adopted some of these same methods and developed them further.  He would pour acid on his patients backs and cut them with knives to allow the discharge “form the neighborhood of the brain”.  Rush also developed the famous “tranquilizer chair” where patients were restrained for up to entire days — the chair had a convenient hole for defecation at the bottom.

Bloodletting was used to treat a number of ailments.  It also often led to death.  One famous incident involves George Washington, who in 1799 suffered from a bad sore throat and died shortly after a visit by three different doctors who, altogether, took about half of his blood volume. The famous medical journal The Lancet derives its name from the tool used in these procedures.

Given Singer and Gruen’s depiction of animal research one must also ask — How did human surgeries look back then?  By all accounts they were the most excruciating, traumatic and dangerous experience for patients.  As an example, the novelist Fanny Burney recounted part of her experience with a mastectomy as follows:

I mounted, therefore, unbidden, the Bed stead & M. Dubois placed me upon the Mattress, & spread a cambric handkerchief upon my face. It was transparent, however, & I saw, through it, that the Bed stead was instantly surrounded by the 7 men & my nurse. I refused to be held; but when, Bright through the cambric, I saw the glitter of polished Steel I closed my Eyes. I would not trust to convulsive fear the sight of the terrible incision. Yet — when the dreadful steel was plunged into the breast cutting through veins arteries flesh nerves I needed no injunctions not to restrain my cries. I began a scream that lasted unintermittingly during the whole time of the incision & I almost marvel that it rings not in my Ears still? so excruciating was the agony. When the wound was made, & the instrument was withdrawn, the pain seemed undiminished, for the air that suddenly rushed into those delicate parts felt like a mass of minute but sharp & forked poniards, that were tearing the edges of the wound. I concluded the operation was over Oh no! presently the terrible cutting was renewed & worse than ever, to separate the bottom, the foundation of this dreadful gland from the parts to which it adhered Again all description would be baffled yet again all was not over, Dr. Larry rested but his own hand, & — Oh heaven! I then felt the knife (rack)ling against the breast bone scraping it!

Ms Burney was lucky to have survived to describe her experiences.  Most surgeries taking place in surgical theaters simply ended up in death.

The above were some of the common practices of medicine a mere 200 years ago. Magendie was one among the main critics of the dominant medical theories (humorism and vitalism) and the use of unproven methods on human patients. On the use of animals in research he said at a meeting [] I beg my honorable colleague to observe that I experiment on animals precisely because I do not wish to experiment on men.  That is what he felt about medicine — it was nothing short of human experimentation.

In the introductory pages of his Journal de Physiologie Expérimentale Magandie, he added:

“What subject is indeed more fertile in gross errors and absurd beliefs than that of health and disease? Consider the painful disquietude you would produce in the minds of the majority of men if you said to them:There are no such things as rheumatismal humour, gouty humour, scabby virus, venereal virus, and so forth.  Those things which are so designated are imaginary things, which the human mind has created to hide from itself its own ignorance.’   The chances are that you would be taken for a lunatic just as it but recently befell those who maintained that the sun was immovable and the earth turned.”

Any honest reading of medical history has to give credit to the experimental physiologists who put medicine in the right track to become what it is today. The handful of physicians and psychiatrists that speak against animal research should remember that from Hippocrates to the early 19th century, their profession caused more harm than good to their patients.  They ought to be reminded that it was the work of the experimental physiologists that turn this around.  Charles Darwin acknowledged this fact when he wrote:

[] I know that physiology cannot possibly progress except by means of experiments on living animals, and I feel the deepest conviction that he who retards the progress of physiology commits a crime against mankind.

As experimental medicine advanced, so did our ability to treat the potential pain and suffering animals may experience in research.  Animal welfare laws were established. Today, the vast majority of animals participating in research benefit from the use of modern anesthetics and analgesics. The public and our representatives recognize that responsible, regulated animal research has continued to produce new therapies and cures through the years — benefiting humans and non-human animals alike. Stopping the work and depriving future generations of new advances would be immoral.

Birth of Pro-Test Israel

The following guest post is written by Shaul Peretz, a former Israeli investigative journalist and founder of Pro-Test Israel.

Three years ago I learned about Mazor Farm, a small farm located in Moshav Mazor, in central Israel, and the country’s only farm breeding monkeys for biomedical research. All the information about the farm on the Internet came from animal rights activists, who described horror stories.

They said the monkeys are kidnapped from Mauritius and taken to Israel, where greedy dealers sell them to the highest bidder for experimentation, including cosmetic toxicity tests.

For ten years of my life, I was an investigative reporter for the major Israeli newspapers Yedioth Ahronoth and Ma’ariv so I was curious about these claims. Frankly, I found it hard to believe what was written. I began to research animal experimentation is Israel and discovered that the claims being made by activists were a mix of lies and half-truths.

In truth, monkeys are not kidnapped. Rather, the government of Mauritius is begging research laboratories to take as many monkeys from the island as they can. Monkeys on Mauritius are considered to be a pest by the International Union for Conservation of Nature and the local government so they control the population by euthanizing them. So the truth is that the fate of the monkeys in Mauritius is death by local authorities or being used for biomedical research for life-saving experiments.

macaque monkey animal testing israel

The monkeys at Mazor Farm are kept in large outdoor corrals

Investigating further, I discovered that macaque monkeys are not used for cosmetic testing, as claimed by opponents, but only for biomedical research to save lives and prevent suffering. Furthermore, contrary to activists’ claims, cosmetic testing on animals is prohibited in Israel, as it is in almost every other country.

I discovered that research using monkeys at Mazor Farm resulted in:

For many years, scientists in Israel have been threatened by animal rights activists. We determined that the person behind the threats against Prof. Moshe Abeles, Director, Institute for Brain Research at Bar-Ilan University, was Anat Refua, who might be called an Israeli equivalent of U.S. activist Camille Marino.

I tried to join the Facebook pages of animal rights activist including “Together we close the Mazor Farm” to bring the real information to the attention of its readers, but it was a lost cause. I was soon censored and blocked from writing. Animal rights activists support “freedom of speech” only if it is theirs. So I created two pages “Uncensored truth about animal research and monkeys” and “animal research is saving lives” that are designed to tell the truth about what animal research is and what it has given us.

macaque monkey animal research israel

The large outdoor areas allow the animals to socialise and play

As a result of our successful activities, animal rights activists began to harass and try to frighten me. They published an image of my then-young daughter, and I had to file a complaint with the police to protect my family.

They set up a page with a similar name to our page (“uncensored truth about research”) and called it “The official page.” As a result, some people who are looking for our page accidentally go to their page and read more lies about animal research.

Top contributors to our page who are physicians, researchers, and medical students have received threats in their personal email accounts.

We are going through a period of a great struggle against opponents of animal research. The Israeli media has given a lot of publicity to the growing trend toward veganism, a practice that many activists share.

The previous Environment Minister of Israel, Gilad Ardan – whose office signs the permits needed to export monkeys from of Israel – has added restrictions as a result of pressure from activists. The new regulation will prohibit the export of monkeys for biomedical research starting in January, 2015, although there is no restriction on importing monkeys to Israel for research here. Mazor Farm is expected to close since Israeli research institutions need only around 30 monkeys per year.

Our investigation revealed what is behind this decision. A month before a hearing was held into the future of Mazor Farm, Environment Minister, Gilad Arden received a private donation from the chairman of Let the Animals Live (comparable to PETA), which was actively trying to close the farm. A State Control judge is now investigating this.

monkey animal experiment playingTwo years ago, Israel’s largest airline, El Al, succumbed to activist pressure and stopped transporting any animals for research and lifesaving biomedical research. As a result, research institutions in Israel must charter private flights at a cost of tens of thousands of euros (Israel has no land transportation option).

However as a result of the activists’ tactics, public feeling in Israel is turning against them. In academia, people are starting to wake up and try to counter the lies.

Many wrote to the new environment minister, Amir Peretz, asking him to change the regulation and allow the export of monkeys for biomedical research so that Mazor Farm can continue. Hundreds of Israeli researchers and doctors have signed a petition to this effect.

As result of our activity and the spread of factual information – the activists lost their “exclusive ownership” of the publicly available information. More and more people in Israel understand the importance of animal research and confront activists’ claims on Facebook and elsewhere.

In the UK, US and Italy, scientists and members of the public have stood up against animal rights misinformation. Through the Pro-Test movements, activists have been challenged on their lies and harassment – this is what Israel needs. This is why I am founding Pro-Test Israel, to bring people together to defend the research behind life-saving medical research. I hope many will join me. If you wish to find out more, click here (website in Hebrew).

I am optimistic that the activist tactics will not last long:

You can lie all the people some of the time,
You can lie to some of the people all the time,
But you cannot lie to all the people all the time.

Shaul Peretz

Animal rights fanatics offer stunts, not real solutions

This post is simulposted with the Unlikely Activist blog, run by this post’s author, David Jentsch.

Fanatical animal rights groups in the US love attention-getting stunts. PeTA creates video games extolling violence and propagates advertisements that exude adolescent sexuality. White Coat Waste uses Tea party rhetoric to insist federal investment in research is tantamount to borrowing money from China. And the Humane Society of the United States [HSUS] reels endless videos of sad animals on the television to raise money for their lobbying efforts, while tricking people into thinking their donations actually help animals in shelters.

An animal rights extremist group, White Coat Waste, uses Tea Party rhetoric in an attempt to undermine support for research investment

An animal rights extremist group, White Coat Waste, uses Tea Party rhetoric in an attempt to undermine support for research investment

These are stunts, nothing more – nothing less.

In Los Angeles, local animal rights zealots are trying hard to carve out their own niche in the “stunt” art form. They light candles during vigils on the beach, hand out post cards decrying UCLA researchers at art events and recite chants in eerie synchrony, while standing in front of our homes. In truth, the occasional bizarre chanting during these stunts is slightly less demented than their usual shrieks, threats and harassment.

Later this month, the ironically named anti-science group – Progress for Science – will mount an 11-day campaign to “honor” the 11 monkeys they believe are involved in scientific research projects at UCLA. They will probably once again come to my home and threaten my neighbors, while trying to make my life miserable.

But if Progress for Science truly has the respect for life than they claim they do, perhaps they should consider a different strategy. Perhaps before mounting their 11 day campaign for 11 hypothetical monkeys, they should find it in their hearts to lead initiatives for real people affected by real disease. For example, they could:

Lead a 930 day campaign for the number of Africans that have died from Ebola so far this year.

Initiate a 4,600 day campaign for the young people in our country who took their own lives last year, often due to mental illness.

Kick off a 1.1 million day campaign for the number of people living with HIV in the US.

Support a 2.2 million day campaign for the people suffering from or disabled by schizophrenia in this country.

Demand an 8.2 million day campaign for the number of people that will die from cancer in one single year, worldwide.

Health care providers and patients rally in support of mental health services

Health care providers and patients rally in support of mental health services

It is, of course, true that multi-million day campaigns are impossible, but biomedical researchers in many cases dedicate their entire working lives to addressing the harm in these diseases: our own life-long campaigns. Animal rights fanatics could contribute positively to these efforts, rather than standing in the way of progress, but they won’t do that because they are not actually interested in preserving life. They are interested in stunts.

If you are interested in preserving life, then please support biomedical research, including that which involves animals. This year alone, two Americans received a treatment for Ebola that was developed based upon animal research and that likely saved their lives. This is the promise of science. Stunts, on the other hand, contribute nothing, save no lives and end no suffering.

David J. Jentsch

Responsible Antibody Production

Antibodies Part 2 (read Part 1 here)

As noted in our previous post, there are many promising uses for antibodies. Therefore, it is no wonder that antibody production is big business. The Scientist reported that revenues from antibody sales were over $1.6 billion in 2011. In the United States, antibody producers that use regulated species of animals must comply with the Animal Welfare Act, just as research institutions that use animals must do.

Earlier this year, we reported that one large antibody producer, Santa Cruz Biotechnology (SCB), was accused by the United States Department of Agriculture (USDA) of numerous animal welfare violations. The company originally planned to address these allegations at a USDA administrative law hearing scheduled for the week of July 14, 2014. That hearing has since been postponed while SCB and the USDA try to reach a negotiated settlement on the alleged violations. We would welcome such a settlement if the end result is better animal welfare practices at SCB.

Mice in a Cage

“We would welcome such a settlement if the end result is better animal welfare practices at SCB.”

Meanwhile, the USDA recently announced a settlement with another antibody producer: Rockland Immunochemicals, Inc.  Rockland paid a $32,071 fine for multiple Animal Welfare Act violations in 2012 and 2013. It is noteworthy that all inspections of Rockland Immunochemicals by the USDA thus far in 2014 have indicated that the company was compliant with the Animal Welfare Act. Hopefully, Rockland has learned an important lesson: animal welfare matters

Neither Rockland Immunochemicals nor Santa Cruz Biotechnology discusses corporate responsibility or their commitment to animal welfare on their websites, but other antibody producers do. For example, the Aves Labs website plainly states its commitment to animal welfare and heralds the fact that the company voluntarily sought accreditation of its animal use program by the Association for the Assessment and Accreditation of Laboratory Animal Welfare (AAALAC).   Protocols describing the company’s use of animals for antibody production are also provided on its website.

Other examples of antibody producers with strong commitments to animal welfare and transparency in animal use include ImmunoPrecise, Pocono Rabbit Farm and Laboratory, EMD-Millipore, and Bethyl Laboratories.

We urge all antibody producers to establish corporate responsibility practices and transparency regarding their animal use programs. We also urge scientists and pharmaceutical companies to weigh the producers’ commitment to these important values in selecting which antibodies to use.

Alice Ra’anan and Bill Yates

Pregnancy Kits to Ebola Treatment: Medical Tests & Disease Treatments Depend on Animal Products

Antibodies Part 1

There has been considerable discussion on this website about the use of animal studies to develop new medical treatments. But some animal-derived products such as antibodies also play a crucial role in diagnostic tests for some diseases and targeted treatments for others. In the last week, antibodies hit the front pages of newspapers and websites with the news that the ZMapp serum given to 2 Americans aid workers stricken with the deadly Ebola virus was a cocktail of antibodies. Developed through research in mice, the two components of this experimental serum – ZMab and  MB-003 – had only previously been tried in monkeys, but the results were very promising. As of this writing, both aid workers’ conditions had improved.

Mice played a critical role in developing the antibodies used to treat aid workers with Ebola. Tweet this!

Antibodies are proteins the immune system produces to identify and neutralize foreign objects such as bacteria and viruses. Antibodies “recognize” specific proteins, a property that makes them highly useful for a variety of purposes. For instance, antibodies can be used in diagnostic tests to determine whether a protein associated with a particular disease or medical condition is present in a patient’s blood, urine, saliva, or tissues. The home pregnancy test is an example of a diagnostic test that relies on antibodies. These tests detect the hormone human chorionic gonadotropin, a protein that is only present during pregnancy.  Many other medical tests also utilize antibodies; a few examples are:

  1. Tests to look for heart proteins in the blood such as troponin that indicate that a heart attack has occurred.
  2. Tests for the presence of the HIV (AIDS) virus in the blood.
  3. Tests for proteins present in the blood of patients with Lupus, an autoimmune disease where the immune system attacks the body’s own tissues.

A diagram showing the characteristic Y shape of an antibody molecule. It is able to grab two of its target molecules with the ends of the two arms of the Y.

Antibodies can also be used to treat disease. Certain antibodies can neutralize toxins such as snake venom.  Other antibodies are coupled to a toxin or other chemical, such that it is delivered only to cells carrying the protein that antibody recognizes.  For example, some cancer cells generate unique proteins so antibody-coupled drugs can be used to deliver a toxic agent to the cancer cells without harming other cells in the body. Antibody therapies have been effective in treating a number of types of cancer, including Hodgkin lymphoma and non-Hodgkin lymphoma, some forms of skin cancer, and some forms of breast cancer. Now we learn that antibodies may also be effective in treating Ebola.

Unique cell surface proteins on a cancer cell, which can be detected using antibodies.

Unique cell surface proteins on a cancer cell, which can be detected using antibodies.

There are two types of antibodies used for medical diagnostics and treatments: polyclonal antibodies and monoclonal antibodies. Both require animals in their production.

Polyclonal antibodies are produced by injecting the protein of interest (or part of it, called an antigen) into an animal.   Since this is a foreign substance, the animal’s immune system reacts to it by generating antibodies to fight off the intruder. Later, samples of the animal’s blood are removed and the antibodies isolated. Larger animals such as sheep, goats, and rabbits are often used for antibody production because they have enough blood in their bodies that large blood samples can be removed without harming them. Antibodies generated using this method are called “polyclonal,” because they came from many different immune cells known as B cells or B-lymphocytes.

Process for producing polyclonal antibodies

Process for producing polyclonal antibodies

To produce monoclonal antibodies, an animal (often a mouse) is injected with the partial protein or antigen of interest. Antibody-producing cells are later isolated from the animal, often from its spleen. Fast-growing but harmless tumor cells are cultivated in the lab and fused with the isolated antibody-producing cells. This produces a new cell type called a hybridoma that can be grown in the lab. Once it is confirmed that the hybridomas are generating antibodies against the right antigen, these hybrid cells can serve as factories to grow large numbers of pure monoclonal antibodies in the lab.

From: FASEB’s Breakthroughs in Bioscience Series.  Used by permission.

Monoclonal antibody production process

Alice Ra’anan and Bill Yates

To learn more about the role of animal research in advancing human and veterinary medicine, and the threat posed to this progress by the animal rights lobby, follow us on Facebook or Twitter.

Behaviourists Defend Basic Science

The August issue of the journal Animal Behaviour contained a commentary “Time to step up: defending basic science and animal behaviour.” The authors, Dr. Patricia Brennan, Dr. Rulon Clark and Dr. Douglas Mock begin by providing a history of how it became politically fashionable to ridicule basic scientific research. The Golden Fleece Awards were started in 1975 by Senator William Proxmire to provide examples of frivolous spending. Unfortunately, several federally funded research projects fell under Proxmire’s scrutiny and had small pieces of information exaggerated or distorted to seem completely ridiculous. The practice continues to this day and was last written about here in 2010. The mocking of basic science provided some people short-term political gains with unknown long-term national costs.

The bitter partisanship existing within the USA and challenges over budget appropriations the authors discuss strategies for how scientists can defend their work if they are the focus of unwarranted political or media attention.   The commentary outlines what researchers can do before or after one is targeted. Who should be informed, what to say and nine talking points to drive home the importance of basic science.

Talking points

  1. Basic science is the foundation of all applied science. Because we cannot predict which basic science projects will turn into an application, we must cast a wide net.
  2. The connection between basic and applied science is seldom a straight line; more often, it involves a network that connects novel ideas, methods and data in a new way, leading to innovations.
  3. The government must fund basic science because its potential economic gains are unpredictable and generally long term. No private investing company can invest under those conditions.
  4. Government investment in science guarantees that at least some of our discoveries are free of special interests, and therefore it protects the integrity of the scientific process. Federal investment in research and development was only 24% of all U.S. science investment in 2008 .
  5. Funding decisions at NSF, NIH and other agencies are made by panels of scientists who judge projects on the basis of their intellectual merit and impact to society.
  6. These agencies are severely underfunded and, as a result, many high-priority projects do not get funded.
  7. The return on investment estimated from government funding of science is enormous. Not all projects turn a profit, but when they do, they can transform society: think Google, Taq polymerase and green fluorescent protein (GFP).
  8. Federally funded basic science projects are the engine of many research universities. Without these projects, universities could not train the next generation of scientists. Involvement in basic research is often the highlight of a student’s undergraduate experience and provides training that cannot be replicated through coursework.
  9. Organisms are exquisitely adapted to their environment and the study of these adaptations has allowed us to make great strides in medicine and technology.

“Not responding to politically motivated attacks is likely to be the wrong strategy. Silence may further erode public confidence in science, as it may be interpreted as implicit acceptance that there is something wrong with your project.”

They also include several examples of fundamental behaviour research that have had unanticipated significant impacts. For example:

The Sexual Behaviour of the Screwworm Fly

One of the recipients of a Golden Fleece Award was E. F. Knipling for his research into the sex life of parasitic screwworm flies. Knipling developed the sterile male technique to eradicate this cattle pest, based on observations during the 1930s that male screwworm flies will mate with many females, while females will mate only once. He used this information to devise a male sterilization strategy using X-rays. He released sterile males into the population and in a few generations completely eradicated this parasite. Knipling’s $250,000 grant from the Department of Agriculture led directly to a program estimated to have saved at least $20 billion for U.S. cattle producers. The sterile male technique is currently used as a standard eradication technique on many agricultural pests.

Screwworm Fly

Neuroplasticity and Neurogenesis in the Brain

The discovery that humans can grow functional neurons in the brain during adulthood is revolutionizing the understanding of learning and memory, recovery from brain injury and disease, and the effects of addiction and neurodegenerative diseases. Several of the most influential early studies that discovered adult neurogenesis in the brain were conducted by Fernando Nottebohm, who showed that seasonal changes in the song nuclei of male canaries, Serinus canaria, were explained by recruitment of new neurons and death of old ones. Nottebohm also showed that black-capped chickadees, Poecile atricapillus, grow neurons associated with spatial memory in the brain during the autumn, perhaps to facilitate finding their food caches during the winter months, further supporting a role of learning on neurogenesis. Nottebohm was an avid birder from childhood and his interests were centred on understanding how and why birds sing. When Nottebohm published his first papers on neurogenesis in the avian brain, the central dogma of neurobiology was that no new neurons grew in adult brains, but his careful and continued work served as a platform to develop new ideas on neurogenesis and neuroplasticity.

Atlantic Canary

Host Manipulation by Parasites

Studies of host manipulation by parasites were not begun by behavioural ecologists, but they have embraced this field in the last two decades, rapidly advancing the grasp of how parasites change host behaviour. The study of parasite manipulations has important applications to conservation, agricultural production and medicine. One of the iconic examples involves infection of carpenter ants by the trematode Dicrocoelium denditricum, which affects wild and domestic ruminants. Ants are the intermediate host of this trematode, and the larvae form cysts that make the ants climb grass blades and grasp the top securely until a grazer comes by and eats it, thereby completing the parasites’ life cycle. In humans, toxoplasmosis infection has been linked to a variety of mental disorders, and this link has been particularly well studied in schizophrenia. Many studies have shown that schizophrenic individuals are more likely to be seropositive for antitoxoplasma antibodies. Moreover, Toxoplasma gondii appears to have major effects on human behaviour, including several personality traits.

The authors finish their commentary by stressing the need to educate the public, engage the younger generation, increase social media presence, train scientist to communicate science to the general public and support them actively communicating their findings. The recommendations to defend the need for basic science presented in the current edition of Animal Behaviour are relevant not only to this field but all scientific diciplines across the world.

Michael Brunt

Harlow Dead, Bioethicists Outraged

harlow plaque jpeg (2)

The philosophy and bioethics community was rocked and in turmoil Friday when they learned that groundbreaking experimental psychologist Professor Harry Harlow had died over 30 years ago. Harlow’s iconic studies of mother and infant monkeys have endured for decades as the centerpiece of philosophical debate and animal rights campaigns.  With news of his death, philosophers worried that they would now need to turn their attention to new questions, learn about current research, and address persistent, urgent needs in public consideration of scientific research and medical progress. Scientists and advocates for a more serious contemporary public dialogue were relieved and immediately offered their assistance to help others get up to speed on current research.

To close the chapter, psychologists at the University of Wisconsin provided the following 40 year retrospective on Harlow’s work and its long-term impact (see below).

Internet reaction to the scientists’ offering was swift, fierce, and predictable.

“We will never allow Harlow to die,” said one leading philosopher, “The fact is that Harlow did studies that are controversial and we intend to continue making that fact known until science grinds to a halt and scientists admit that we should be in charge of all the laboratories and decisions about experiments. It is clear to us that we need far more talk and far less action. Research is complicated and unpredictable–all that messiness just needs to get cleaned up before research should be undertaken.”

Animal rights activists agreed, saying:

“For many decades Harlow and his monkeys have been our go-to graphics for protest signs, internet sites, and articles. It would simply be outrageously expensive and really hard to replace those now. Furthermore, Harlow’s name recognition and iconic monkey pictures are invaluable, irreplaceable, and stand by themselves. It would be a crime to confuse the picture with propaganda and gobbledygook from extremist eggheads who delusionally believe that science and animal research has changed anything.”

Others decried what they viewed as inappropriate humorous responses to the belated shock at Harlow’s passing.

“It is clear to us that scientists are truly diabolical bastards who think torturing animals is funny. Scientists shouldn’t be allowed to joke. What’s next? Telling people who suffer from disease that they should just exercise and quit eating cheeseburgers?” said a representative from a group fighting for legislation to outlaw food choice and ban healthcare for non-vegans and those with genetic predispositions for various diseases.

A journalist reporting on the controversial discovery of Harlow’s death was overheard grumbling, “But what will new generations of reporters write about? Anyway, the new research is pretty much the same as the old research, minus all the complicated biology, chemistry, and genetic stuff, so it may as well be Harlow himself doing it.”

A fringe group of philosophers derisively called the “Ivory Tower Outcasts” for their work aimed at cross-disciplinary partnerships in public engagement with contemporary ethical issues made a terse statement via a pseudonymous social media site.

“We told you so. Harlow is dead. Move on. New facts, problems require thought+action (ps- trolley software needs upgrade, man at switch quit)”

Harlow himself remained silent. For the most part, his papers, groundbreaking discoveries, and long-lasting impact on understanding people and animals remained undisturbed by the new controversy.

Statement from Psychologists:

Harlow’s career spanned 40+ years and produced breakthroughs in understanding learning, memory, cognition and behavior in monkeys1 (see Figure 1). In a time period where other animals were generally thought of as dumb machines, Harlow’s work demonstrated the opposite — that monkeys, like humans, have complex cognitive abilities and emotional attachments. Harlow and his colleagues developed now classic ways to measure cognition2,3. For example, the Wisconsin General Test Apparatus (WGTA; see Figure 1), in which monkeys uncover food beneath different types of colored toys and objects, allowed scientists to understand how monkeys learn new things, remember, and discriminate between different colors, shapes, quantities, and patterns.

The discoveries of Harlow and his colleagues in the 1930s and forward provided the foundation not only for changes in how people view other animals, but also for understanding how the brain works, how it develops, and –ultimately–how to better care for people and other animals.

Figure 1

Figure 1

In the last decade of his long career, Harlow, his wife Margaret– a developmental psychologist, and their colleagues, again rocked the scientific world with a discovery that fundamentally changed our biological understanding.3 Contrary to prevailing views in the 1950s and before, the Harlows’ studies of infant monkeys definitively demonstrated that mother-infant bonds and physical contact—not just provision of food—are fundamentally important to normal behavioral and biological development. Those studies provided an enduring empirical foundation for decades of subsequent work that shed new light on the interplay between childhood experiences, genes, and biology in shaping vulnerability, resilience, and recovery in lifespan health.

For a brief time at the very end of his career, Harlow performed a small number of studies that have served as the touchstone for philosophers, animal rights groups, and others interested in whether and how animal research should be done. The most controversial of the studies are known by their colloquial name “pit of despair” and were aimed at creating an animal model of depression. In this work, fewer than 20 monkeys were placed in extreme isolation for short periods (average of 6 weeks) following initial infant rearing in a nursery.

At the time, the late 1960s, the presence of brain chemicals had recently been identified as potentially critical players in behavior and mental illnesses like depression and schizophrenia. New understanding and treatment of the diseases was desperately needed to address the suffering of millions of people. Available treatments were crude. They included permanent institutionalization– often in abject conditions, lobotomy (removing part of the brain), malaria, insulin, or electric shock therapies. As some scientists worked to uncover the role of brain chemicals in behavior and mood, others worked to produce drugs that could alter those chemical networks to relieve their negative effects. In both cases, animal models based on similar brain chemistry and biology were needed in order to test whether new treatments were safe and effective. It was within this context that Harlow and his colleagues in psychiatry studied, in small numbers, monkeys who exhibited depressive-like behaviors.

By the 1970s and over the next decades, scientists produced medications that effectively treat diseases like schizophrenia and depression for many people. The therapies are not perfect and do not work for everyone, which is why research continues to identify additional and new treatments. Regardless, there is no question that the suffering of millions of people has been reduced, and continues to be alleviated, as a result of new medications and new understanding of the biological basis of disease.

Infant rhesus monkeys playing in nursery.  Wisconsin National Primate Research Center. @2014 University of Wisconsin Board of Regents

Infant rhesus monkeys playing in nursery. Wisconsin National Primate Research Center. @2014 University of Wisconsin Board of Regents

Looking back while moving forward

Nearly 50 years later, it is difficult to imagine the time before MRI and neuroimaging and before the many effective treatments for depression, schizophrenia and other diseases. It is perhaps even more difficult to imagine a time in which people believed that genes and biology were destiny, that other animals were automatons, or that mothers were only important because they provided food to their children. Casting an eye back to the treatment of monkeys, children, and vulnerable human populations in medical and scientific research 50 years ago, or even 30 years ago, is difficult as well. Standards for ethical consideration, protections for human and animal participants in research, and the perspectives of scientists, philosophers, and the public have all continued to change as knowledge grows. Yet, what has not changed is an enduring tension between the public’s desire for progress in understanding the world and in reducing disease and the very fact that the science required to make that progress involves difficult choices.

There are no guarantees that a specific scientific research project will succeed in producing the discoveries it seeks. Nor is there a way to know in advance how far-ranging the effect of those discoveries may be, or how they may serve as the necessary foundation for work far distant. In the case of Harlow’s work, the discoveries cast a bright light on a path that continues to advance new understanding of how the brain, genes, and experiences affect people’s health and well-being.

Mother and infant swing final

Mother and juvenile rhesus macaque at the Wisconsin National Primate Research Center. @2014 University of Wisconsin Board of Regents

 

 

 

 

 

 

 

In the 30 years since Harlow’s death, new technologies and new discoveries—including brain imaging (MRI, PET), knowledge about epigenetics (how genes are turned on and off), and pharmacotherapies—have been made, refined, and put into use in contemporary science. As a result, scientists today can answer questions that Harlow could not. They continue to do so not because the world has remained unchanged, or because they lack ethics and compassion, but because they see the urgent need posed by suffering and the possibility of addressing global health problems via scientific research.

Harlow’s legacy is a complicated one, but one worth considering beyond a simple single image because it is a legacy of knowledge that illustrates exactly how science continues to move forward from understanding built in the past. An accurate view of how science works, what it has achieved, what can and cannot be done, are all at the heart of a serious consideration of the consequences of choices about what scientific research should be done and how. Harlow and his studies may well be a touchstone to start and continue that dialogue. But it should then be one that also includes the full range of the work, its context and complexity, rather than just the easy cartoon evoked to draw the crowd and then loom with no new words.

Allyson J. Bennett, PhD

The author is a faculty member at the University of Wisconsin-Madison.  The views and ideas expressed here are her own and do not necessarily represent those of her employer.

Suomi SJ & Leroy, HA (1982) In Memoriam: Harry F. Harlow (1905-1982). American Journal of Primatology 2:319-342. (Note: contains a complete bibliography of Harlow’s published work.)

2Harlow HF & Bromer J (1938). A test-apparatus for monkeys. Psychological Record 2:434-436.

3Harlow HF (1949). The formation of learning sets. Psychological Review 56:51-65

4Harlow HF (1958). The nature of love. American Psychologist 13:673-685.