Macaque study explores best route of oxytocin administration

Oxytocin is a natural brain peptide most commonly thought of as the “love hormone” for its role in social bonding: it spikes during social contact, play, cuddling, and sex. Because of extensive research in animals including prairie voles, sheep, and monkeys demonstrating that oxytocin promotes affiliative behaviors and social bonding1,2, oxytocin is increasingly being studied for its effects on humans3. The jury is still out here: some studies show that oxytocin has no effect on social behavior, whereas others show a negative effect. The most attention, however, is given to those studies showing a positive effect, particularly in individuals with social deficits like those with autism spectrum disorder (ASD)4.

Consequently, oxytocin nasal sprays are increasingly being advertised as treatments for ASD, despite the inconclusive results from clinical trials and a lack of studies showing their long-term efficacy and side effects. These sprays are available online without a prescription but they are not regulated by the FDA. Thus little is known about the quantity of oxytocin they contain, their efficacy, or possible side effects.

Though nasal sprays are commonly used in clinical trials for ASD, oxytocin is often administered intravenously (IV). In both cases, study designs differ in the amount of oxytocin they use, the duration of treatment, and the delivery method, so it is no surprise that they have yielded conflicting results. Thus, the mechanisms by which oxytocin administered in different ways may act in the brain are unclear.

Macaque Monkey

Image Credit: Amanda M. Dettmer

An important and timely study just published online in Psychoneuroendocrinology by researchers at the California National Primate Center and the University of California-Davis tackles some of these methodological questions. Rhesus monkeys were implanted with intrathecal catheters to allow for repeated sampling of cerebrospinal fluid (CSF) in awake animals, and were treated with either intranasal (IN) or IV oxytocin at three different doses in a randomized, crossover study design (meaning animals were randomly assigned to IN, then IV, or vice versa). Blood and CSF samples were collected from awake animals (thus eliminating possible confounds of anesthesia) pre-dose (0 minutes), and at 5, 15, 30, 60, and 120 minutes after oxytocin administration. Importantly, this is the first study to use awake monkeys for oxytocin administration and sample collection, to directly compare more than two different doses of oxytocin in the same subjects, and to collect five concurrent post-oxytocin blood and CSF samples in a relatively short period. These methods would be extremely difficult, if not impossible, to carry out in human subjects.

The researchers found that blood and CSF levels of oxytocin were higher after IV vs. IN administration. Furthermore, they found that IV-administered oxytocin elevated blood and CSF oxytocin for a period of up to 30 minutes, whereas IN oxytocin had no effect on blood levels of oxytocin, regardless of the dose – an unexpected finding because IV oxytocin does not cross the blood-brain barrier5. The authors postulate that elevated levels of oxytocin in the bloodstream after IV oxytocin treatment might result in the release of oxytocin in the brain (as observed in CSF) via mechanisms that have yet to be identified, but which studies using nonhuman primate models will be critical for disentangling. They also argue that humans can be instructed to inhale deeply during IN administration, whereas animals cannot, yielding important methodological implications for studies relying on animal models of human behavior. Finally, the group reported that blood oxytocin cannot be used as a reference for CSF oxytocin (thus supporting earlier findings), yet most human studies rely on measuring blood oxytocin after oxytocin treatment.

The authors conclude that, “…it is…critical to use nonhuman primate models to better evaluate the effectiveness of the delivery method most commonly used in human studies and clinical use – the nasal spray.”6 Indeed, studies like this one are critical for informing dosing regimens and administration methods of oxytocin in humans, as we cannot conduct such detailed studies without animal models. Ultimately, animals – specifically nonhuman primates – will be key for identifying and understanding the mechanisms by which oxytocin and other drugs act to affect brain and behavioral responses.

Amanda M. Dettmer

References

  1. Stoesz, Hare & Snow, 2013, Neurosci Biobehav Rev, 37(2):123-32.
  2. Lim & Young, 2006, Hormones & Behavior, 50:506-17.
  3. Kuehn, 2011, JAMA, 305(7):659-61.
  4. Young & Barrett, 2015, Science, 347(6224):825-26.
  5. Ermisch et al., J Cereb. Blood Flow Metab, 5:350-57.
  6. Freeman et al., 2016, PNEC, 66:185-94.

Community Outreach: Talking about the animals

Many of us that work in biomedical research often are confronted with the dreaded question: “What do you do for a living?” The anxiety of the inevitable conversation about animal research can be palpable. One may ask, “Do I tell them the truth and get into a debate about the ethics of animal research? Or do I tell them that I am an accountant, thus avoiding any further conversation about my career?” Although distorting the truth works, but it does a great disservice to all those involved. How will people really understand animal research unless accurate, balanced information is provided? Historically, the majority of the information available is from science journals or biased animal rights groups. As a result, the bulk of the information is skewed to paint animal research as a vile, unethical institution that cares little about the animals. On the other hand, science journals describe the science, written for scientists. How does the lay person get that accurate information? That accurate information comes from you, the one that works in the industry.

It is important to note that I do not speak for all individuals in this field, but the sentiment behind my words is shared by the vast majority. Those of us that have chosen to work in this field have done so for very specific reasons:  Some of us do it to be a part of human and/or animal medical advances; others do it because they feel passionate about animal welfare and, of course, there will always be a few people who do it solely because they like having a steady job with a steady paycheck. Fortunately, the vast majority of people in the industry do not subscribe to the latter reason.

The fact that many people disapprove of animal research, but nearly all benefit from it, indicates that most people do not truly understand how biomedical research works. From food and drug production to vaccines, surgical and disease treatments, humans have benefited from animal research for hundreds of years. The sheer shock that the public has in reaction to animal research stories indicates that more education is needed. For example, the A.L.S. ice bucket challenge was all the rage last year, yet some people complained they did not want their charitable dollars to go towards animal research. The fact that some people did not know that all medical testing and treatments have or will go through animal testing before use in humans demonstrates the lack of education regarding the system. It is now time to explain it. When it comes to public opinion it is important to understand that people’s perception of complicated and controversial subjects is dramatically affected by the available information to which they are exposed. We can thank the biased animal rights groups for providing the bulk of the misinformation about research that exists today. They have had years to twist the truth and present their information in a way that immediately causes negative emotional responses in those that are subjected to this information. That is the same stance those of us in research must take. We must talk about what we do, but it should be made personal. This is the only way the lay person will be able to relate, at the personal level.

When I think of a personal story that describes the environment of research as well as the people and animals, I think of Duncan. Duncan was a chimpanzee I had the honor to know while working as a veterinary technician. Since he didn’t have a family group, he had to be housed singly, along with three other lone males. We were tasked to give them a little extra attention. Although I spent time with all of the males, Duncan was, by far, my favorite. I spent many hours over the years sitting next to his enclosure and talking to him. Of course, he would nod and grunt at me, not allowing me to feel too crazy speaking to an animal. One day, Duncan became sick. He had saculitis (inflammation of his air sacs) that was not responding to treatment.   After weeks of diligent care, Duncan succumbed to his disease. I was holding him and petting him the day he passed. As he lay breathing his last breath, I looked around me. All I saw was a family crying over the loss of a member. From care techs to managers and veterinarians, we all cried together. The loss of this amazing creature shook everyone to the core. This pain can only be compared to the loss of a human loved one. I felt great comfort in knowing that we all mourned Duncan and that we, as the caregivers that did more than just feed him, we loved him.   It is with stories like this, that the true face of biomedical research can be seen, from great love and compassion. These are the stories we need to tell.

CC-BY-NC-SA

Creative Commons BY-NC-SA: kathyweststudios@gmail.com

Once an individual is empowered to speak up about research and tell their story, as I was through Duncan, the next step is to determine the outlet and the audience. Anyone can get involved with outreach; locally or nationally. Some examples are: Institute of Animal Technology (IAT), American Association for Laboratory Animal Science (AALAS), technical schools, local career days, contributions to web sites publishing articles about science and, of course, casual conversation. Please see the end of this article for links to various avenues for outreach.

Regardless of the platform for outreach, the target audience should always be considered. Formulate your discussion, lecture, presentation or article around the individual that will be receiving the information. If the bulk of your audience is not science based, avoid scientific jargon- speak in plain terms. Most importantly, explain how your work has or may improve medicine as if you are speaking to someone with no knowledge of the inner-workings of research.

Now that you have a story to tell, you may ask yourself: Why should I speak out? The answer is clear.   The people with the best knowledge of the inner workings of research are the best source of information. It is time that the research community counteracts the years animal rights groups have had to speak against research. The best way to counteract those effects is to be open about what we do and how we do it. We should inform the public by providing balanced information. Let them make their own decisions but with correct information, instead of skewed rhetoric that serves only to fuel the extreme views that all animal research is bad and managed by heartless people that do not care about animals or society. Each one of us should be proud of our careers. It is time to show your pride and tell the world what we do and why we do it. We, the research community, are in favor of ethical treatment of animals for biomedical research and would prefer a world where disease did not need to be studied. We would also prefer a world where there was effective and appropriate alternatives for animal research, however, none are currently available or reliable to use for all research. Until that day comes, we will continue to provide the best care we can- not only because it is the law but because it is the right thing to do.

James Champion

Speaking of Research accepts guest posts from researchers, technicians, veterinarians, and those involved in outreach. If you are interested in writing a post for us, please contact us.

Guest Post: Obama’s Cancer Initiative and Animal Research

This is the one of the first posts of a new FBR blog which aims to provide people with relevant, timely and scientifically substantive information about how biomedical research is saving lives. This post was originally posted here, and is reprinted with permission from the Foundation for Biomedical Research. This blog was posted for yesterday’s World Cancer Day.

During his recent 2016 State of the Union Address, President Obama took aim at cancer. Promising to “make America the country that cures cancer once and for all,” the President tapped Vice-President Biden to lead the national effort that will focus on immunotherapy, genomics, and combination therapies to “make a decade worth of advances in five years.”

While animal research is an essential part of biomedical research, it plays an even bigger role in the fight against cancer. What follows are highlights of some of the most promising discoveries and therapies.

cancer-vaccine2

Immunotherapy Drug Development

Immunotherapy is a form of treatment that recruits a patient’s own immune system to fight cancer. Recently, genetically modified animal models have led to a host of effective new immunotherapy drugs.

Glioblastoma Multiforme (GBM) is the “most dangerous and aggressive” type of brain cancer. A diagnosis means a median survival time of 14.6 months. Current therapies, such as specialized chemotherapy, can add 2.5 months to survival, but they only work for less than half of GBM patients.

Immunotherapy offers much promise in treating GBM cancer by modifying the immune response in a way that slows or stops the spread of cancer cells. Current immunotherapies for brain cancer fall into ‘six broad categories’; cancer vaccines, checkpoint inhibitors, oncolytic virus therapy, adoptive cell therapy, adjuvant immunotherapies, and monoclonal antibodies.’

Several new immunotherapies targeting GBM promise to increase the survival rate. One, Rindopepimut, recruits the immune system to attack cells harboring a specific protein that only appears on the tumor. Once clinical trials are finished we will learn all of the animal models used to develop Rindopepimut – public data at present shows that researchers used mouse models in the early phases of creating the drug.

Mice are not the only animal helping to advance GBM research – dogs, zebrafish and fruit flies are also important models of the disease. Dogs have a long history as a valuable partner in cancer research. Dogs can develop spontaneous GBM in a manner similar to people. Researchers are currently giving dogs who have developed GBM cancer spontaneously cutting-edge immunological treatments with the hope of extending their lives and gleaning insights into fighting GBM that could also help people. The University of Minnesota operates a program that has treated over 150 dogs and advanced therapies for both dog and human cancer.

There are also impressive immunological approaches being used to treat other forms of cancer.  Nivolumab, commercially known as Opdivo, is a drug that helps the immune system’s T cells fight cancer in the body. Results have  improved on prior treatments; some patients with highly advanced melanoma have even had their cancer eliminated entirely.

Development and testing of Nivolumab used animal models extensively. Much of the research relied on genetically modified mice, known as PD-1 knockout models. Other animals used include rats, rabbits, and cynomolgus monkeys.

Cell-Based Therapy

Cell-based cancer therapy is a unique strategy wherein a patient’s own T cells are collected from his or her blood and genetically manipulated to be more effective cancer fighters. In CAR T-Cell Therapy, the T cells are modified to recognize certain proteins that appear on cancer cells, then loaded back into the bloodstream, where they go to work to kill cancerous tumors.

CAR T-Cell Therapy was created and refined by scientists using mice, dogs, and monkeys. The research with dogs led researchers at the MD Anderson Cancer Center to develop CAR therapy for dogs with leukemia. In September of 2015, scientists announced that they had developed and tested a cell therapy that cured glioblastoma in half of the mice treated.

Epigenetic Therapy

Epigenetics is the study of cell traits variations that are not caused by encoded DNA but rather by external and environmental factors that can switch genes on or off and affect how a cell reads genes. Epigenetics is what allows stem cells to become specialized types of cells, but may also lead to cancer. Recently, researchers have developed increasingly successful drugs by targeting epigenetic enzymes that regulate the cell. Most cancer treatments seek to kill the cancerous cells; epigenetic drugs make the cancerous cells return to their normal state.

One of the most successful epigenetic drugs, called AG-221, recently put 25 out of 45 patients with acute myeloid leukemia (AML) into remission with minimal side-effects. AG-221 is still in FDA testing, so all of the species of animals used are not yet publicized, but it is known that mouse models were essential to the drug’s development.

Research in Metastasis

Metastasis is the process that causes some cancer cells to break off from the original tumor and take root in a different tissue. Metastasis causes nine out of ten deaths from cancer and there have been few advances in survival rates.

Years of research have led scientists to a better understanding of metastasis. They have identified genes and pathways that drive the spread of cancer and discovered survival methods it uses – and which may be turned against it in future therapies.

Animal models have played a large role in advancing metastasis research. Scientists at Cold Springs Harbor Laboratory used new techniques to create an advanced mouse model of metastatic prostate cancer. By precisely mimicking aspects of the illness, the mouse model will allow scientists to investigate the causes of the disease while also testing new therapies to treat it.

Similar specially-bred mouse models are also used in studying metastatic breast cancer, bone metastasis, and colon cancer metastasis, to name just a few.

Foundation for Biomedical Research

Open Letter to the Australian Senate regarding a proposed bill to ban the import of primates

The following letter has been sent to the Committee Secretary of the Senate Standing Committees on Environment and Communications regarding the Environment Protection and Biodiversity Conservation Amendment (Prohibition of Live Imports of Primates for Research) Bill 2015. This proposed bill would ban the Australian research community from importing primates for use in biomedical research. The following is a segment of the proposed amendment:

Australian Bill

We encourage the scientific community to leave comments of support for our letter in the comment section below.

Dear Committee Secretary,

Nonhuman primate research has played an important role in many medical breakthroughs, from the polio vaccine to the development of life support systems for premature babies.

Studies with nonhuman primates are a small fraction of basic, behavioural, and biomedical research; however, they are critical to scientific research that seeks to address health issues of grave concern to the public. Nonhuman primate research includes studies relevant to understanding, preventing, and treating a range of diseases including, Alzheimer’s, Parkinson’s, stroke, HIV/AIDS, hepatitis, anaemia and a multitude of mental health conditions.

Thanks to research on primates:

  • Polio has been eradicated from Australia, saving tens of thousands of children from crippling disability
  • Thousands of Australians have had Deep Brain Stimulation to alleviate the symptoms of Parkinson’s
  • Over 20,000 HIV positive Australians can live a relatively normal life thanks to the development of antiretrovirals
  • Australian children can be vaccinated against Hepatitis B, diphtheria, measles, mumps and rubella

Measures to constrain nonhuman primate research in Australia puts future medical breakthroughs in jeopardy.

Australian law already bans the use of wild caught nonhuman primates for research (as does the EU). Such laws should continue to be actively enforced to uphold animal welfare standards, but importantly, should not be expanded to prevent important nonhuman primate research being conducted.

Preventing researchers from importing nonhuman primates could prevent scientists from responding to public health issues or new areas of biomedical research in Australia and beyond. The domestic supply of nonhuman primates may be able to provide for most of the needs of the scientific community, but also risks constraining it. Any future Australian research would be limited to species of monkeys currently bred in Australia’s three breeding colonies, effectively restricting the animal models available to the biomedical community.

Research conducted with nonhuman primates is strictly regulated. All research must be approved by Animal Ethics Committees, who apply the 3 Rs framework to ensure that animal studies are Replaced wherever there is a non-animal alternative, Refined to ensure animal suffering is minimised, and Reduced to ensure that as few animals are used as is necessary to produce scientifically viable results. Animal welfare remains a high priority for the scientific community – with animal care personnel and veterinary staff providing round-the-clock care for their wards.

Yours faithfully,

Speaking of Research

Inês Albuquerque
Jeremy Bailoo, Ph.D
Prof Mark G Baxter
Prof Allyson Bennett
Paul Browne, Ph.D
James Champion
Paula Clifford
Amanda M. Dettmer, Ph.D
Prof Doris Doudet
Jazzminn Hembree RLATG
Tom Holder
Prof J. David Jentsch
Juan Carlos Marvizon, Ph.D
Kimberley Phillips Ph.D
Prof Dario Ringach
Simon R Schultz, DPhil

Background Briefing on Animal Research in Germany

Speaking of Research have now added a fourth background briefing on animal research to our list. We now have a German background briefing – in both English and German – to add to our briefings on the US, UK and Canada. We hope this briefing will offer journalists, politicians and the public a short, handy overview of the key facts. Our two-page summary provides information including the number of animals used for research purposes, the laws and regulations surrounding animal research, and some key questions people have.

Download our background briefing on animal research in Germany [or in German]

As with our previous briefings, we encourage those working in universities, pharmaceuticals, and other research institutions, to help share this document when contacting or responding to journalists about research stories relating to their institution. By attaching this background briefing to proactive stories, or reactive statements, it can help ensure that your research is understood within the context of the wider research environment.

We would like to thank Pro-Test Deutschland – particularly Renee Hartig, Florian Dehmelt and Jennifer Smuda – for their help in gathering information on the German legislation, and for translating the German-language version of the document.

The latest version of all our briefings can be found on both the Multimedia resources page, and in the menu system under Facts->Animal Research Briefings.

See a sample of the briefing below:

Briefing note on animal research in Germany

We permit anyone to redistribute this briefing providing it remain unchanged, and in whole, with credit to Speaking of Research.

We would also like to thank the Science Media Centre (in the UK), who’s “Briefing Notes on the Use of Animals in Research” provided the inspiration for our own.

Speaking of Research

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.

Please consider supporting the activities of Speaking of Research. We are asking our readers for small individual contributions (up to $15/€10) to help us pay our $150 website costs for 2016. See more here.

Animal Research Statistics for Northern Ireland 2014

While England, Scotland and Wales (collectively “Great Britain”*) are regulated by the UK Home Office and produce one set of statistics together, Northern Ireland is regulated by the Department of Health, Social Services and Public Safety in Northern Ireland, which produces its own statistics.

According to the Department of Health, Social Services and Public Safety in Northern Ireland, in 2014, there were 19,857 procedures on 18,889 animals*. Most of these were on mice (12,946), but there were also a significant number of pigs (690), sheep (781), cattle (1,661), birds (1,376), and rats (605). In 2014 there were 72 cats (down 17%), and 156 dogs used in research (up 113%) – mainly for translational/applied studies (though 57 dogs were used for regulatory purposes). No primates were used in either 2013 or 2014.

*animals are only counted the first time they are involved in research, so an animal which is used in different projects in both 2013 and 2014 is only included in the 2013 “number of animals”, but will be included in the “number of procedures” for both 2013 and 2014.

CC-BY: www.speakingofresearch.com

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Compared with the previous year, there were 3 fewer animals used, a relatively insignificant drop from 2013. Rats and fish both fell as a proportion of the total, but the number of procedures on birds rose.  Also, given the change from reporting the number of procedures in started studies, to reporting the number of procedures in completed studies, comparisons to previous years should be taken with a pinch of salt.

CC-BY: www.speakingofresearch.com

Click to Enlarge

Other things to note from the statistical release:

  • Creation and breeding of genetically altered animals not used in experimental procedures accounted for 15% of all procedures, much lower than the 60%+ in the rest of the UK. Most procedures (49%) were for basic research, followed by Applied/Translational Studies (30%) and Regulatory (4%). [Table1]
  • 69% of research went on in Universities and medical schools, 25% was in non-profit-making organisations and 6% were in commercial organisations. [Table 11]
  • For the first time the Northern Ireland statistics include retrospective reporting of suffering. Rather than just submitting licence proposals to the DHSSPSNI that include estimated levels of suffering, the researchers now have to report on what was actually seen (using a variety of measures). Unfortunately the statistics put these in two separate tables (Table 3 and 8). So we have combined them to get severity for all procedures in 2014. We can see most experiments are sub threshold (4%; less than the introduction of a hypodermic needle) ormild (62%), with remainder as moderate (28%), severe (6%) or non-recovery (0.3%; the animal never awakes from anaesthesia). [Tables 3 and 8]

CC-BY: www.speakingofresearch.com

It should be noted that despite Northern Ireland using over 100 times fewer animals than the rest of the UK, is still holds itself to the same high quality of statistical reporting.

Lastly, by adding the statistics for Great Britain (3,867,439) to those of Northern Ireland (19,857), can see that 3,887,296 procedures on animals were conducted in the United Kingdom in 2014. Nonetheless, when referring to the UK stats throughout most of the website, we will actually be referring to Great Britain.

We are hoping to see 2014 reports for Denmark, the Netherlands, New Zealand and Poland soon.

Speaking of Research

*The statistics for Great Britain tend to be referred to as the “UK Stats”. While this is not technically correct, it is perhaps not too surprising, given that Great Britain accounts for over 99.5% of the UK’s animal experiments.

See the full Northern Ireland statistics here: https://www.dhsspsni.gov.uk/sites/default/files/publications/dhssps/asp-statistics-of-scientific-procedures-on-living-animals-ni-2014.pdf

Read last year’s release here:

http://speakingofresearch.com/2014/11/25/animal-research-statistics-for-northern-ireland-2013/

PR, ethics, and the science of head transplants

There has been a lot of media coverage on the recent claims by Dr. Sergio Canavero that he has successfully transplanted the head of a monkey on to a donor body of another monkey. This story, originally posted by the New Scientist, has since gone viral with some touting miracle cures for paralysis, while others have publicly expressed outrage and disgust. As pointed out by the New Scientist, this is not science, or at the least, not yet. Until the veil of secrecy concerning the conduct of this study is made transparent – no formal conclusions can be made and one can only speculate in regards to the quality of the experiment that was performed. Moreover, as this work still has to pass through the peer-review process, it remains unclear whether this is simply an attempt at publicity. As Arthur Caplan, a New York University bioethicist told New Scientist:

It’s science through public relations. When it gets published in a peer reviewed journal I’ll be interested. I think the rest of it is BS”

So far, the only evidence that Dr Canavero has produced is a picture of a monkey which appears to have had a head/body transplant, as well as a short video of a mouse moving around (despite significant impairments), which also appears to have a transplant (but how long did they live for? When Dr Canavero’s colleague Dr Xiaoping Ren of China’s Harbin Medical University carried out similar head transplants in mice in 2015 they all died within a few minutes of being revived after surgery). While the monkey “fully survived the procedure without any neurological injury of whatever kind”, according to Canavero, it was euthanized after 20 hours for “ethical reasons”. The media storm surrounding this story appears to play up to the researcher’s aims – to find financial backing to continue his research and then move it into humans.

Canavero at TEDx

Two pieces of information in the article by the New Scientist bear scrutiny. The first is that Canavero is quoted as saying “this experiment, which repeats the work of Robert White in the US in 1970, demonstrates that if the head is cooled to 15°C, a monkey can survive the procedure without suffering brain injury.” Second, Sam Wong, author of the article in the New Scientists stated “they connected up the blood supply between the head and the new body, but did not attempt to connect the spinal cord.” Careful reading highlights a simple fact, this study is not novel in any regard – this is a replication of the work by Robert White and is quite simply a “head transplant”. Thus, the same criticisms that were levied in regards to the original experiment by Robert White apply here. As Stephen Rose, director of brain and behavioural research at Open University can be quoted as saying in 2001:

This is medical technology run completely mad and out of all proportion to what’s needed. It’s entirely misleading to suggest that a head transplant or a brain transplant is actually really still connected in anything except in terms of blood stream to the body to which it has been transplanted. It’s not controlling or relating to that body in any other sort of way. It’s scientifically misleading, technically irrelevant and scientifically irrelevant, and apart from anything else a grotesque breach of any ethical consideration. It’s a mystification to call it either a head transplant or a brain transplant. All you’re doing is keeping a severed head alive in terms of the circulation from another animal. It’s not connected in any nervous sense.”

And so, it is worth reflecting at this juncture on the moral and ethical issues surrounding this controversial procedure. Let us assume for a moment that this procedure is in fact feasible. In the original studies by Robert White and Vladimir Demikov, it was made clear that these experiments were lethal for the animal. Simply put, while the head of the animal was capable of “seeing, hearing, tasting, smelling”; none of the other regulatory processes were intact (e.g. breathing) as there was no control over the donor body. Furthermore, like many tissue transplants, rejection of the donor body from the immune system is a large possibility, immunorejection was after all the cause of death in the monkey whose head Dr White transplanted in 2001. Indeed, Canavero has yet to demonstrate any kind of proof of principle with regeneration of nervous tissue with any meaningful metric of control of the donor body.

Perhaps the most interesting insight into Canavero’s thinking comes from a quotation in the New Scientist article where he says:

Gene therapy has failed. Stem cells, we’re still waiting. Even if they come now, for these patients there is no hope. Tetraplegia can only be cured with this. Long term, the body decays, organs decay. You have to give them a new body because even if you take care of the cord, you’re going nowhere.”

These remarks by Canavero are somewhat naive as both gene therapy and stem cell therapy have made substantial advances in recent years, with many therapies now in clinical trials. Furthermore, the claim that “Tetraplegia can only be cured with this [head transplant]” flies in the face of evidence from recent successful animal and clinical trials on a variety of innovative therapies for paralysis, including epidural stimulation, intraspinal microstimulation, neuroprosthesis, and stem cell therapy.

There have recently been a series of major advances in treating paralysis, including epidural stimulation.

There have recently been a series of major advances in treating paralysis, including epidural stimulation.

While there is mounting evidence from studies in rodents that the polyethylene glycol (PEG) implantation approach favored by Canavero may be able to promote repair of injured spinal cord and recovery of motor function in paralyzed limbs, his casual dismissal of the work of other scientists – while often simultaneously citing their work in support of his own approach – exemplifies his arrogance. He would be better off lending his expertise to the work of others who are exploring the potential for PEG in spinal cord repair, work that has the potential to benefit millions of people, but instead appears set on a self-aggrandizing PR campaign in support of an approach that if successful – which seems highly unlikely even if the surgery is a technical success – can only benefit a tiny number of people…potentially at the cost of depriving many other transplant patients of much needed organs.

The reality, however, remains that the procedure exposes the patient (be it mouse, monkey or human) to far greater risks compared to the potential benefits. Indeed, these experiments would never be approved in countries which have strict review criteria, with a clear harm/benefit analysis needing to be performed before such a study is given approval. In these circumstances, the news that leading experts in animal research in China are currently undertaking a major revision to the country’s national regulation on the management of laboratory animals is timely.

But these issues are not unknown to Dr. Canavero. Indeed, as can be seen here (scroll to see response), and in what can only be described as derision and a willful skirting of the law, Dr. Canavero remains set to push forward with his ideas regardless of the consequences. For these reasons we have the gravest of reservations about the course being followed by Dr. Canavero and his colleagues, and call on them to halt this research until a full independent review of the scientific evidence and impact on potential patients can be undertaken.

Jeremy Bailoo and Justin Varholick

The opinions expressed here are our own and do not necessarily reflect the interests of the the University of Bern or the Division of Animal Welfare at the University of Bern.