Briefly, my position is based on the notion of graded moral status.  I believe we owe moral consideration to all living beings, but not in equal degree.  This idea is direct conflict with those that promulgate that all living beings have the same basic rights to life and freedom. Thus, it is no surprise that in a recent post, Rick Bogle, an animal rights proponent and former advisor to the Animal Liberation Front Press Office, takes aim at such ethical positions.

He should know it was not an animal researcher that concocted the idea of graded moral status. The notion is one that has been discussed by moral philosophers for some time.  It is a theory that is accepted as a valid and defensible position in the literature, and I cited the work of David DeGrazia as one example.

To the proponents of animal rights the notion of graded moral status cannot be accepted at any cost.  Any such acceptance would amount to accepting a version of animal welfarism.  Instead, they are of the belief that all living beings have the same basic rights to life and freedom.

Why?

Mr. Bogle explains:

It seems to me that in times of great danger, the desires and interests of humans and members of many other species are exactly the same. If threatened, we run or hide.

Concluding:

In these fundamental matters [...] our interests are identical.

In short, Mr Bogle thinks that any organism that runs or hides when threatened must be considered to have the same mental states, the same interests in life and freedom and, as a consequence, the same moral status as that of humans.

One may point out that that even single-cell organisms will “run away” from “threats” — such as the movement of bacteria by chemotaxis.  And one may wonder if Mr. Bogle believes that bacteria have the same moral status as a humans.

Indeed, he thinks we ought to give the bacteria the benefit of the doubt:

We don’t have a testable theory to explain mind. In the absence of such, all we have is observable behavior. When mollusks, bees, monkeys, or foreigners behave as if they are acting with intention, a consistent moral course demands that they be given the benefit of the doubt.

In other words, when a single cell moves towards glucose Mr. Bogle suggests we interpret the behavior as intentional: “the cell enjoys glucose and makes a voluntary decision to seek places where it can be found in high concentrations.”

Really?!

In a nutshell — Mr. Bogle demands society to stop all biomedical research with animals aimed at the continuing advancement of medical knowledge, human and non-human health because “it seems” to him that “the desires and interests of humans and members of many other species are exactly the same”.

And this is, of course, how he justifies his support of violence against scientists.

One of multiple articles where Bogle justifies the use of violence against scientists.

Mr. Bogle, at the same time, is also the Executive Director of Alliance for Animals, an organization that supposedly “advocates for non-violence and respect”.  And yet, he is neither non-violent nor respectful.

If your moral intuition and reason tell you to be suspicious of Bogle’s animal rights claims, you would be right to do so.  Given the serious implications that stopping the work would have on human and non-human suffering, scientists and the public are likely to demand a more reasonable objection. Specifically, those that oppose the research must justify the morality of inaction.

Understanding the range of existing outreach activities, current venues for public access to information, and level of participation in these various activities is the foundation for an informed evaluation and reasonable discussion of progress in this area. Reviewing some of those efforts is the subject of this initial post.

Those who engage in scientific outreach and education efforts find that members of the community welcome opportunities to hear from us and to learn about other views of animal research. The great majority are interested in knowing more about why we believe animal research is essential, how we treat animals in our care, and how our studies may contribute to improvements in human and animal health.  There is no shortage of public interest in learning more about animal research.

What are the sources of information about animal research that are freely available to the public? Among them are:

• Websites of research institutions, scientists, scientific societies, government agencies, advocacy organizations, educational organizations, laboratory animal research associations, and medical charities.
• Scientific papers and books in which animal researchers write not only about their findings and methods, but also about the rationale for their studies and why the findings are important.
• Publicly-available databases listing federal grant funding for animal research projects
• Facility records and inspection reports available via the federal agency charged with oversight of animal research, the United States Department of Agriculture.

In addition to these, there are a large number of materials that are available to the public via federal Freedom of Information Act requests or open records requests at the state level.  In fact, it is via this well-known and often-used avenue that animal activists obtain a range of documents that can then be placed on their websites in order to share with the broad community.  Although there is variance across the states, it is also true that in some state universities, the meetings of the committee (Institutional Animal Care and Use Committee) that evaluates each proposal for an animal research project are also open to the public.

Beyond publicly-available information, there are also many efforts by individuals, institutions, and organizations to provide dynamic interactions and opportunities for dialogue. We’ve written previously about why public education and dialogue are important and about the many different paths to accomplish this goal.  Those include:

• Community and classroom programs
• Public discussion forums
• Televised debates
• Social media, including blogs
• Individual interactions

It is against this backdrop that the animal research community and research advocates reject the stock, broad criticism that there is little openness or engagement on this issue.  It is certainly the case that specific types of engagement, or specific forms of openness, that some animal rights activists desire are not supported, but that is a different complaint and discussion. Do all institutions exhibit adequate openness at all times? Probably not. But neither should sweeping complaints about researchers’ lack of engagement be accepted at face value.

There are a number of considerations that can influence differing perspectives on the need for, or the merit of, particular approaches to dialogue and information-sharing about animal research. Continuing to focus narrowly on specific requests, without acknowledging the many existing venues, efforts, and activities for exchange of information on animal research, works against the claim that activists are genuinely interested in dialogue. That narrow perspective also fails to consider that the goal of many of these efforts is to reach the larger audience and public that has broad interest in medical research in general, and is not just interested in the ethical debate over the use of animals in biomedical research.

On May 2nd 2012 the BiteBack extremist website reported that Riccó Alete, an Italian supplier of laboratory equipment, and SD Pellicceria, an Italian fur store, both had their websites defaced (apparently) by the notorious hacking group Anonymous.

Two days later, on May 4th 2012, Anonymous targeted  the website of Anlaids, an Italian non-profit organization which aims to tackle AIDS through information, research and funding.

However, this problem is not limited to Italy, or even Europe, on May 10th 2012 an American pet product company website was taken down by activists due to the activities of their sister-organization, Marshall BioResources, who supply equipment for laboratories.

Message left by hackers

Anonymous, for those who are unaware, is a loose collective of hackers from all over the world. Their effectiveness can be gauged from their high profile targets. They have (temporarily) crashed the websites of the Syrian Defence Ministry, the British Home Office, the US Department of Justice, Interpol and even the FBI.

Nonetheless, we should put this on perspective. As mentioned before, the number of anonymous members involved in the attacks on companies linked to animal research is very small – probably just one. The nature of anonymous is that anyone may carry out attacks in their name (it is a front group in this respect) and although they have a history of anti-establishment attacks, they do not have a history of targeting those linked with animal research.

Cheers

Tom

It is thus encouraging to read in Nature today an update on how these efforts by scientists have allowed a paralyzed patient to reach for a cup, bring it to her lips, and drink from it.

Critical milestones in the development of motor prosthesis for paralyzed patients

As explained in a nice News and Views piece by Andrew Jackson that accompanies the article, this type of work builds on decades of previous research on the neural mechanisms that control arm movements (here, here and here) (blue on the Fig above), on the development of chronic multi-electrode arrays (orange), their recording properties in animals, and on feasibility studies of neural interfaces in monkeys (here, here, here and here) (green), which opened the way to clinical studies in humans (here and here) (purple).

The value of animal research should not be difficult to grasp. The knowledge that allows us to “read out” the planned movements of the patient from different brain regions in order to guide the movement of the robot is critical in the design of the system.  And it is an indisputable fact that such knowledge has been (and continues to be) obtained by experiments in awake, behaving monkeys.

And for those that doubt the true motivation of scientists for doing their work, it is worth noting what Dr. Leigh Hochberg (one of the leading authors of the study) had to say about their results – “The smile on her face … was just a wonderful thing to see.”   Do you want to see her smile too?  Watch this:

Of course the BrainGate system used by Dr. Hochberg and Dr. John Donoghue - director of the Institute for Brain Science at Brown University - is not the only brain-machine interface system under development to restore function in paralysis. In 2008 we wrote about a similar brain implant developed by Dr. Andy Schwartz at the University of Pittsburgh which enabled monkeys to manipulate robotic hands with unprecedented dexterity. Last year we wrote about how Dr. Schwartz’s team had used a different technology known as electrocorticography to enable a paralysed man to manipulate a robotic arm, while Dr. Chet Moritz and colleagues at Wachington National Primate Research Centre, have coupled readings from individual nerve cells to a technology called functional electrical stimulation to restore control to temporarily paralysed muscles in monkeys, an approach that may eventually supersede the use of robotic arms in some patients. It will be fascinating to watch this technology progress into more widespread clinical use over the next decade, and thrilling to think that, impressive as it appears today, we have barely begun to tap the potential of brain-machine interface technology to change lives.

According to de Waal there are compelling ethical reasons to ban all invasive work on chimps, but he argues that one should “not throw out the baby with the bathwater by also curtailing non-harmful behavioral research” as well.  He defines ethically permissible research in chimps as “the sort of research I would not mind doing on human volunteers.”

While Prof. de Waal ought to be applauded for sharing his views on the use of chimps in scientific research, I think he moves too fast through weak and vague ethical reasoning to reach his main conclusion.

Opponents of animal research, for example, are likely to point out his definition of ethically permissible research should read instead “the sort of research [one] would not mind doing on human volunteers who also agree to live in captivity in the same conditions as the chimps.” 

They will also point out that human subjects that volunteer in scientific research, whether invasive or behavioral, provide their informed consent.  Moreover, human subjects retain a right to withdraw their participation at any point in time, and they are never deprived from their liberties and freedom.  Opponents of research will further argue harm comes to these animals by the mere fact they are forced to live in captivity.

It is unclear how de Waal would defend his work from the stated position in his perspective. Perhaps the “special moral status” de Waal wants to grant to chimps and other great apes is not meant to be interpreted as including the same basic rights to liberty and freedom as those enjoyed by humans.  If so, he should state this clearly.  His position is vague and confusing because in the same perspective he seems to approve some countries granting great apes legal rights.

There are other problems that emerge from de Waal ill-articulated ethical position.  He states the basis for awarding great apes special moral status is based on their high cognitive skills, as well as their capacity to display empathy and pro-social behavior. At the same time he believes the same intrinsic properties are present in varying degrees in other species – “there are many differences between chimps and monkeys in cognitive capacities, but we consider them mostly gradual differences.” Given such graded abilities it is not clear how de Waal would draw a line between those species that deserve such “special moral status” and those that do not.  Or if there are other morally relevant properties that he did not mention.

Finally, I think de Waal correctly points out that humans should not be allowed to blame nature to explain our history of violence, warfare, and male dominance.  The reason is that only humans are capable of reflecting on the question of how is that we should treat others, including non-human living beings.  Yes, we have a moral obligation to consider the interest of other living beings in our actions.  But, as Carl Cohen explained, we should not confuse our moral obligations to other living beings with them having basic rights. Rights entail obligations, but the reverse is not always true.

There is wide agreement (and I concur) that the interests of great apes deserve high moral consideration, more so than those of a mouse or a worm. But it is worth noting that such principle of graded moral status is already implicitly acknowledged in the NIH guidelines which require scientists to use the “lowest” possible species that can yield the information they seek.  In this regard, the IoM panel finding that there is only a minimal need to use chimps in scientific research is not a truly reflection of their inadequacy to model disease (chimps could certainly be used in many studies to answer good scientific questions), but of our existing recognition that they deserve high moral status and that they can only be used under the most  extreme circumstances.

This important public education initiative from The Kavli Foundation, the Gatsby Charitable Foundation, and the Society for Neuroscience is an exciting development.  Leading scientists from around the world form the editorial board who will provide an authoritative source of information on neuroscience research.

According to the web site its goal will be to inform the public about exciting discoveries related to brain structure and function; provide science educators with easy-to-use, fun, scientifically valid resources, to use in — and beyond — the classroom; explore the growing understanding about the biological foundations of neurological and psychiatric diseases that affect about one billion people worldwide; and spark dialogue about the progress, potential, and importance of neuroscience research.

BrainFacts.org will provide an authoritative source of information about brain research.

The site already contains useful information on the role of animals in brain research.  One section describes the steps and regulations in animal research, another explains the the use of animal models, and yet another gives specific examples on the advancement of medical knowledge that resulted from the use of animals in research.  Interviews with researchers exemplify how to communicate animal research to the public.  There is also information of particular interest to policymakers.  Finally, the site offers answers to some common myths about the brain, and if you have a question, you can always ask an expert.  A large coalition of scientific organizations will generate content for the site.

You can follow BrainFacts on both FaceBook and twitter.

Welcome BrainFacts!

David Abbott

I am a scientist leading a biomedical research program investigating the causes of polycystic ovary syndrome (PCOS) in women. I see a balanced consideration at the heart of the argument concerning our humane use of about 200 female rhesus monkeys in experimental procedures over the past 20 years in the service of reducing suffering in approximately 15 million American women who endure PCOS. Our systematic and responsible experimental investigation, which was approved after a thorough ethical evaluation by a University of Wisconsin Institutional Animal Care and Use Committee (IACUC), was the first to conclusively identify developmental origins for this women’s health disorder. It is also the first to provide epigenetic molecular insight into potential mechanisms underlying PCOS that can be targeted by future preventive therapies.

PCOS is one of the most common health disorders affecting women. The PCOS ovary makes too much testosterone and supports increased hair growth on the face and body. The enlarged ovary also grows too many egg-containing follicles, thus providing the enigmatic appearance of the polycystic ovary. PCOS follicles usually fail to mature and frequently fail to release an egg at ovulation, hence the lack of menstrual cycles and infertility associated with the disorder. In addition, PCOS overly contributes to obesity, new cases of type 2 diabetes among young women, gestational diabetes, sleep apnea and metabolic syndrome. All of these increase a woman’s lifetime risk of cardiovascular disease. In the words of leading clinical experts in the field:

It has become increasingly clear over the past several years that PCOS is a complex genetic disease resulting from the interaction of susceptibility genes and environmental factors. The insight that prenatal exposure to androgens can reproduce most of the features of the human syndrome in primates has led to a paradigm shift in concepts about the pathogenesis of the disorder.”¹

Our PCOS-like monkeys provide insight into a potential origin for PCOS in women: exposure to too much testosterone during fetal life. This insight cannot be ethically gained from experimentation in humans. The inspiration to explore a fetal origin for PCOS, however, does come from humans. PCOS runs in families. Daughters born to women with PCOS are at increased risk for PCOS. So, I posed the question:  What if excess testosterone production, a hallmark of PCOS and its most heritable trait, is its cause? In other words, could too much testosterone produced by the fetal PCOS ovary reprogram multiple female organ systems as they develop, so that when mature, such widespread organ system dysfunction manifests the abnormalities we know as PCOS? Circumstantial evidence from genetic or tumor anomalies in humans indeed suggests that exposure of fetal girls to excess testosterone, alongside other abnormalities, results in PCOS. Humans, however, cannot ethically be used to test the hypothesis that fetal testosterone exposure, alone, causes PCOS.

A population of female rhesus monkeys housed at the Wisconsin National Primate Research Center at the University of Wisconsin, Madison, held the key to testing this possibility. Between about 1970 and 1985, these otherwise normal female monkeys were exposed to fetal male levels of testosterone during gestation when their mothers were given testosterone conjugate as part of other studies. Independent of this work, I collaborated with an Ob/Gyn specialist, as well as scientists from a variety of biological science disciplines, in a multidisciplinary research approach to examine whether testosterone-exposed female monkey offspring exhibit PCOS traits in adulthood. We proposed controlled and systematic experimental approaches in grant submissions to the National Institutes of Health, who funded this research.

Our work demonstrated that the ovaries of adult female monkeys exposed to testosterone during fetal life produce too much testosterone and, when enlarged, such ovaries grow too many follicles. The testosterone-exposed monkeys also ovulate infrequently, leading to intermittent or absent menstrual cycles. Eggs retrieved from the ovaries of testosterone-exposed monkeys, when fertilized in vitro, show impaired embryonic development. These results from monkey studies led to a human study that demonstrated eggs retrieved from the ovaries of PCOS women had altered gene expression. This was an unappreciated PCOS defect and provided an unexpected mechanism by which PCOS-related abnormalities could be passed from one human generation to the next.

Perhaps the most translatable lessons from the testosterone-exposed monkeys came from examination of their metabolic abnormalities. We found many of the metabolic derangements accompanying PCOS in women, including insulin resistance, impaired insulin response to glucose, type 2 diabetes mellitus (T2DM), hyperlipidemia and increased abdominal fat. As in PCOS women, monkey insulin and glucose impairments were reversed after six months of daily treatment with the insulin sensitizer pioglitazone. The insulin sensitizer approach was so successful that the Primate Center adopted it as the first treatment for all monkeys that developed T2DM naturally since this is known to accompany obesity and aging in monkeys, as well as in humans. Insulin sensitizer treatment of testosterone exposed monkeys also allowed us to normalize their menstrual cycles, demonstrating that insulin is involved in suppressing ovulatory cycles, which also occurs in PCOS women. Thus not only did fetal testosterone exposure create a remarkable mimic of PCOS in monkeys, it emulated a key part of the pathophysiological mechanism found in women with the disorder.

The close replication of PCOS in monkeys prompted examination of what occurs during fetal and infant development before adult PCOS traits emerge, which opens the way to earlier targeting of treatment in humans. We found that testosterone injections given to pregnant monkey mothers actually impaired their ability to regulate blood glucose. In addition, the fatter the monkeys were before they conceived, the more susceptible they were to testosterone diminishing insulin regulation of glucose during pregnancy. As in humans, maternal inability to regulate blood glucose results in increased fetal exposure to glucose and increased fetal and neonatal growth. The infant monkeys previously exposed to testosterone and high glucose as fetuses exhibit high insulin responses to glucose that will likely cause insulin-induced accumulation of fat and muscle and relatively fat offspring beyond their heavier infant weight. Since these infants also have elevated androstenedione levels, reproductive- and metabolic-related antecedents of PCOS in monkeys are pronounced from birth. These findings encourage clinical studies aimed at establishing childhood biomarkers for subsequent adult PCOS, especially since PCOS mothers taking the insulin sensitizer metformin before and during pregnancy give birth to daughters who do not go on to develop ovarian hormonal abnormalities at 2-3 months of age.

More recently, with mapping of the rhesus monkey genome and collection of intra-abdominal (visceral) fat samples from infant and adult monkeys exposed to testosterone as fetuses, we quantified how fetal programming changed the methylation patterns of gene promoter sites, and thus increased or decreased relevant genes expression in a fat depot intimately involved in controlling insulin regulation of glucose. Pathway and network analyses revealed commonalities in changed DNA methylation between infants and adults, implicating altered signaling of transforming growth factor beta (TGF-beta) in determining PCOS-related traits. This is an exceptionally relevant molecular result because a gene variant determining a component of TGF-beta signaling, known as fibrillin 3, has been repeatedly associated with PCOS in women. Fibrillin 3 is also only prominently expressed in human ovaries at a gestational age equivalent to the age at which our monkeys were exposed to testosterone. One aspect of testosterone (and glucose) mediated changes in gene expression in monkeys may therefore provide a molecular mimic of the gene variant associated with PCOS in women. Such molecular mimicry establishes testosterone-exposed monkeys as unparalleled models for establishing preventative therapies targeted at PCOS.

Subsequent testosterone exposure studies on mice, rats and sheep by other scientific teams, undertaken because of the monkey results, emulate some or most of our original findings. While non-primate studies consolidated fetal testosterone exposure as an origin for PCOS traits in adulthood, they also caused fetal growth restriction, something that is not common in women with PCOS and is not found in testosterone exposed monkeys. Fetal growth restriction is caused by diminished placental supply of nutrients and leads to adult metabolic disease distinct from that of PCOS. Testosterone exposed monkeys are thus the most human-like animal model for PCOS and provide an established biological platform for therapy directed studies.

The insight thus gained into developmental programming of PCOS in approximately 15 million women in the US from over 20 years of humane, controlled and systematic use of about 200 rhesus monkeys is substantial and unique. Monkeys are such close human relatives that they best enable translation of research findings into human application. In our case, they permit exploration of insulin regulating therapies during pregnancy, such as metformin, as potential preventative therapies and they permit evaluation of consequences for offspring development, as monkey gestation and infant and juvenile development closely emulate the human. The quality of the scientific findings yielded by our studies was made possible by the highest standards of veterinary care, animal husbandry, nutrition, social housing and environmental enrichment that permit our monkeys healthy and well-cared for lives. Our research program is a humane and considered use of monkeys in the service of reduced suffering in women.

David Abbott, Ph.D.

Department of Ob/Gyn and Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI

1 Dunaif A, Chang RJ, Franks S, Legro RS. 2008. Polycystic Ovary Syndrome. Current controversies, from the Ovary to the Pancreas. Pp. vii. Humana Press, Totowa, NJ.

Dr. Shoukhrat Mitalipov, who led this research project, explains what the project involved and its implications

A press release from OHSU highlights the importance of the Rhesus macaque to this discovery about the inheritance of mitochondial genomes:

“This latest breakthrough, which was conducted in rhesus macaque monkeys because of their similarity to humans, demonstrates the specific stage of early embryonic development when genetic mutations are passed from mother to fetus. This stage, referred to by scientists as “the bottleneck,” occurs when an early embryo called blastocyst, transitions into a fetus.

To conduct the research, Mitalipov and colleagues needed to design a way to mark and track specific mitochondrial genes as they transitioned from egg, through fertilization, to embryo and then to fetus. This was accomplished by combining two separate mitochondrial genomes into one egg cell. More specifically, one-half of an egg cell from a species of Indian-continent rhesus macaque monkey was merged with one-half of an egg cell from a Chinese-continent monkey. Because these animal species have distinct mitochondrial gene sequences (like breeding two distinct species of dogs), their genetics could be tracked closely.

The microscopic manipulation of splitting and uniting two halved egg cells takes specialized skills and expertise, which the Mitalipov lab has developed over a period of several years.

By studying the development of these joined and then fertilized eggs, scientists were surprised to see that eggs transitioned from containing a 50/50 split of genetics to a fetus that contained a nearly 100 percent either Indian or Chinese-based genome.

 We discovered that during early development, each individual cell in the eight-cell embryo would contain varying percentages of the Indian and Chinese rhesus genes. Some would be a 50/50 split. But others would be 90/10 and so on,” explained Mitalipov. “When these percentages were combined as a whole embryo, the average genetic split between the two species was about equal as initially created. However, later during the transition from a blastocyst to fetus, the genetics would swing one way or another. The resulting offspring would have always a genome that is predominantly Chinese or Indian. Our study tells us precisely when this mitochondrial gene switch occurs and how this can lead to disease.”

This finding raises significant questions about validity of currently methods for genetic diagnosis in early embryos, when a woman is known to carry a mitochondrial gene mutation may pass a disease to her children.

The current pre-implantation genetic diagnosis method is to examine genetic disease risk is by taking one cell from an early eight-cell embryo, and then looking for mutations in that one particular cell. This is done to predict if the remaining embryo is mutation-free,” explained Mitalipov.

The problem with this approach is that you may choose a cell that may not have mutations. But that does not mean the remaining cells in an embryo are mutation-free. Our research suggests that such approach could be flawed because diagnosis takes place prior to the stage when an offspring’s mitochondrial genetics is truly established.”

With this new information and with additional data gathered through further research, Mitalipov and colleagues believe that new methods for genetic diagnosis for mitochondrial disease should be located. The research also demonstrates that the Mitalipov lab’s previously developed method for preventing the passing of mitochondrial mutations from mother to child is highly successful.”

It’s an important discovery, one with important implications for preimplantation genetic diagnosis, and we congratulate Dr. Mitalipov and his colleagues at OHSU on their success!

Lee, H., Ma, H., Juanes, R., Tachibana, M., Sparman, M., Woodward, J., Ramsey, C., Xu, J., Kang, E., Amato, P., Mair, G., Steinborn, R., & Mitalipov, S. (2012). Rapid Mitochondrial DNA Segregation in Primate Preimplantation Embryos Precedes Somatic and Germline Bottleneck Cell Reports DOI: 10.1016/j.celrep.2012.03.011

Notice the use of clicker training to get the animals to do simple tasks such as jump on the weighing scales – this reduces any stress that might be caused by trying to force the beagle to do this unwillingly. This is just one of the many enrichment techniques used to improve animal welfare in laboratories around the world.

An excellent example of the value of dogs in biomedical research is provided by a BBC report “‘Heart shrinking’ trial to combat heart failure to begin” on the launch of a multi-centre trial (see clinicaltrials.gov for details) to evaluate whether electrical stimulation of the vagus nerve can reduce cardiac hypertrophy and arrhythmia, and improve heart function in patients with heart failure. The BBC report acknowledges that “The technique is being trialled in humans after it was shown to keep rats and dogs alive for longer” and links to a 2003 paper which found that electrical stimulation of the vagus nerve increases survival in a rat model of cardiac hypertrophy.

This  technique is based on a discovery made in 1984 (1), when scientists showed that an imbalance in the autonomic nervous system – part of the nervous system that acts as a control system functioning and is comprised of parasympathetic nervous system (PSNS) and sympathetic nervous system (SNS) – has a critical role in the induction of lethal ventricular arrhythmias in dogs following heart attack, with an increase in SNS activity leading to abnormal heart rate, heart tissue growth, and heart failure. Over the past decades several drugs have been developed to treat heart failure by reducing heart tissue growth – the ‘heart shrinking’ referred to in the BBC report – and heart rate, for example Ivabradine whose development we discussed recently, but more recently another approach has received attention, modulating the PSNS through stimulation of the vagus nerve in order to rebalance the autonomic nervous system inputs into the heart.

Following a series of studies which demonstrated that stimulation of the vagus nerve could prevent death and improve heart function in a variety rat and dog models of cardiac dysfunction and heart failure (including the study mentioned by the BBC above), scientists demonstrated in that the beneficial effect of vagus nerve stimulation was additive when combined with drugs to treat heart failure in dogs. An open access review of these studies published in 2010 (2) by Professor Peter J Schwartz of the University of Pavia notes that:

An impressive aspect of these experimental studies is that they provide an unusually uniform picture of significant positive effects produced by chronic vagal stimulation in the failing heart. Furthermore, they also provide evidence for the important concept that the mechanism(s) underlying the protective effect of vagal stimulation involve something at least in part independent of the heart rate slowing.”

This result supported a decision to launch the first small phase I clinical trial of this technique in patients with heart failure, led by Professor Schwartz (3), which demonstrated the safety of the technique, and provided early hints of its effectiveness in 8 human patients. The much larger study whose launch was by the BBC uses a device manufactured by Boston Scientific rather than the BioControl Medical device used in the earlier study led by Prof. Schwartz, but is development was equally dependent on the same careful research in dog models of cardiac disease and heart failure.

It’s just one of many examples of why lab such as the one  in the Understanding Animal Research video are so valued by the medical research community.

Regards

Tom Holder

1)      Schwartz PJ, Billman GE, Stone HL. “Autonomic mechanisms in ventricular fibrillation induced by myocardial ischemia during exercise in dogs with healed myocardial infarction. An experimental preparation for sudden cardiac death.” Circulation. 1984 Apr;69(4):790-800.PubMed: 6697463

2)      Schwartz PJ.”Vagal stimulation for heart diseases: from animals to men. – An example of translational cardiology.-.” Circ J. 2011;75(1):20-7. PubMed: 21127379.

3)      Schwartz PJ, De Ferrari GM, Sanzo A, Landolina M, Rordorf R, Raineri C, Campana C, Revera M, Ajmone-Marsan N, Tavazzi L, Odero A. “Long term vagal stimulation in patients with advanced heart failure: first experience in man.” Eur J Heart Fail. 2008 Sep;10(9):884-91. PubMed 18760668

Schwartz, P. (2011). Vagal Stimulation for Heart Diseases: From Animals to Men Circulation Journal, 75 (1), 20-27 DOI: 10.1253/circj.CJ-10-1019

Then I noticed that Kat Arney at the Cancer Research Science Blog had beaten me to it, with an excellent overview of the study and its implications. I recommend that you go straight over and read her blog post.

The Nature paper describing this study can be read here.

A fascinating aspect of this work is that human genetic studies had failed to reveal the role of the Usp9x gene in pancreatic cancer, and it was only when the GM mice studies were undertaken that its importance became clear.  Does this mean that the human genetic studies were misleading? Does it mean that they were useless? Well, that would be thinking like an anti-vivisectionist.  While it’s true that the human genetic studies were initially misleading about Usp9x in pancreatic cancer, it was by combining the information from human genetic studies with that from the GM mouse studies, and the additional information from in vitro studies, that the mechanism through which Usp9x suppression contributes to the development of pancreatic cancer was revealed.

This is yet another example of the important role played by animal studies alongside  many other approaches in medical research, and I hope that it soon leads to much -needed improvments in therapy for pancreatic cancer.

There’s another aspect to this story that is almost as interesting as the science itself.  Many animal rights activists like to claim that leading medical research charities conceal their funding of animal research, indeed just the other week the animal rights activist Peter Tatchell wrote a truly execrable article in the Huffingdon Post which included the claim that:

A disturbing desire for secrecy about animal experiments is shared by a number of respected, high-profile medical charities, including the British Heart Foundation, Cancer Research UK and the Alzheimer’s Society. “

Several comments quickly pointed out that this (along with most other aspects of the article) was factually incorrect, indeed it is difficult to see how the British Heart Foundation could be more open about their animal research. So far as Cancer Research UK is concerned, perhaps somebody should ask Peter Tatchell how issuing a press release, and then discussing their animal research with the BBC and in more detail on their science blog is compatible with “desire for secrecy about animal experiments “.  I guess that Peter Tatchell isn’t one to let the facts ruin a good spin!

Paul Browne