Tag Archives: monkey

Understanding addiction: NIDA article highlights contribution of animal research

Professor David Jentsch is a highly respected UCLA neuroscientist who specialises in the study of addiction, one of the most widespread and serious medical problems in our society today. Sadly, by devoting his career to finding out how to better treat a condition that ruins – and all too often ends – many millions of lives in the USA and around the world every year, David has found himself, his colleagues, and his friends and neighbors under attack from animal rights extremists whose tactics have ranged from harassment, stalking and intimidation, to arson and violence.

Did this extremist campaign persuade David to abandon his research?

No chance!

In 2009 David responded to the extremist campaign against him and his colleagues by helping to found Pro-Test for Science to campaign for science and against animal rights extremism at UCLA, and has been a key contributor to Speaking of Research, writing articles on the role of animal studies in the development of new therapies for addiction, what his studies on rodents and vervet monkeys involve, and how addiction research can help us to understand obesity.

Vervet monkeys involved in David Jentsch's research program live in outdoor social groups to ensure optimal welfare

Vervet monkeys involved in David Jentsch’s research program live in outdoor social groups to ensure optimal welfare

This week the NIH’s National institute on Drug Abuse (NIDA) has published an excellent article on David’s ongoing research entitled  “Methamphetamine Alters Brain Structures, Impairs Mental Flexibility”, which highlights the importance of non-human primate research in identifying how addiction alters the brain and why some individuals are more prone to develop damaging methamphetamine dependency than others. You can read the article in full here.

Human chronic methamphetamine users have been shown to differ from nonusers in the same ways that the post-exposure monkeys differed from their pre-exposure selves. The researchers’ use of monkeys as study subjects enabled them to address a question that human studies cannot: Did the drug cause those differences, or were they present before the individuals initiated use of the drug? The study results strongly suggest that the drug is significantly, if not wholly, responsible”

This knowledge of how drug use disrupts brain function will be crucial to development effective clinical interventions for methamphetamine addiction, and the huge scale and devastating impact of methamphetamine use makes it clear that such interventions are desperately needed, as David highlights in the article’s conclusion.

Methamphetamine dependence is currently a problem with no good medical treatments, when you say a disease like methamphetamine dependence is costly, it’s not just costing money, but lives, productivity, happiness, and joy. Its impact bleeds through families and society.”

At a time when animal rights activists in many countries are pushing to ban addiction research involving animals, the NIDA article on the work of David and his colleagues shows why this work is so valuable, and just what would be lost if animal rights extremists are allowed to have their way.

Speaking of Research

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First human stem cells created through cloning…thank Mitalipov’s macaques!

Today is one of those days that will go down in medical and scientific history, the day that scientists at Oregon Health and Science University led by Professor Shoukhrat Mitalipov announced that they had successfully created pluripotent human stem cells by cloning  skin cells. This is the first time that this has been accomplished in human cells, and is a major milestone in the developing field of regenerative medicine. It is also an achievement that rests on over a decade of careful studies of somatic cell nuclear transfer (SCNT) – the cloning technique they used - in monkeys by Professor Mitalipov and his colleagues.

A donor egg moments after injection of the skin cell nucleus. Image courtesy OHSU photos

A donor egg moments after injection of the skin cell nucleus. Image courtesy OHSU photos

An article on the ONPRC News highlights the importance of research in monkeys to overcoming the barriers that had foiled previous attempts to clone primate cells.

The Mitalipov team’s success in reprogramming human skin cells came through a series of studies in both human and monkey cells. Previous unsuccessful attempts by several labs showed that human egg cells appear to be more fragile than eggs from other species. Therefore, known reprogramming methods stalled before stem cells were produced.

To solve this problem, the OHSU group studied various alternative approaches first developed in monkey cells and then applied to human cells. Through moving findings between monkey cells and human cells, the researchers were able to develop a successful method.

The key to this success was finding a way to prompt egg cells to stay in a state called “metaphase” during the nuclear transfer process. Metaphase is a stage in the cell’s natural division process (meiosis) when genetic material aligns in the middle of the cell before the cell divides. The research team found that chemically maintaining metaphase throughout the transfer process prevented the process from stalling and allowed the cells to develop and produce stem cells.”

While this announcement, coinciding with publication of a scientific paper reporting their work that is published in the prestigious journal Cell (1), was a surprise, the fact that the team was led by Professor Mitalipov was not. Professor Mitalipov is one of the leading experts in reproductive biology, cloning and stem cell biology, and it was only back in March that we discussed how the technique of spindle-chromosomal transfer that he developed to prevent mitochondrial disease had been approved for human trails by the UK’s Human Fertilisation and Embryology Authority.

The key publication by Professor Mitalipov and his colleagues was in 2007 (2) when they reported that they has successfully produced two rhesus macaque embryonic stem cell lines through SCNT.  In their 2010 commentary “Cloning of non-human primate: the “road less travelled by” “ Professor Mitalipov and his co-authors describe this study and  subsequent modifications that they made to the SCNT technique to further improve its efficiency in primates. Their many modifications covered changes to the way in which the nuclei of the cells were visualised and manipulated, changes in the conditions under which the donor nucleus and enucleated egg are fused, and precise regulation of the reactivation of the fused cell. One key innovation was the use of the coat protein from the Sendai (HVJ-E) virus to improve the efficiency of cell membrane fusion between the skin cell nucleus and egg cytoplasm while prolonging the activity of a protein called  maturation-promoting factor (MPF) that keeps the egg in the correct cell cycle stage to allow the introduced nucleus to integrate. Avoiding premature activation of cell division in the egg turned out to be even more difficult  in human cells. Initially the technique they had used successfully in macaques failed to yield stable stem cell lines from cloned human cells, and the problem appeared to be that the eggs were still activating too quickly following fusion, but as Professor Robin Lovell-Badge of the MRC National Institute for Medical Research explained to the Science Media Centre earlier today, they were able to make an additional tweak to their method, by adding a shot of caffeine to the mix.

The idea of using caffeine came from previous experiments they had performed with monkey eggs. Caffeine inhibits certain protein phosphatase enzymes that are involved in the degradation of “maturation promoting factor (MPF)”, a factor that is essential for controlling the cell cycle machinery in the egg.”

It is worth noting that they found that while they could produce embryonic stem cell lines using this technique, macaque embryos created using it failed to develop normally when implanted into female macaques, indicating that while this technique is viable for therapeutic cloning it cannot be used for reproductive cloning.

Professor Mitalipov discusses the first macaque stem cells produced through cloning in 2007.

The potential uses for stem cells produced through this therapeutic cloning technique are myriad; the fact that you can take a person’s own adult cells and convert then into pluripotent cells that can differentiate into any cell type makes them ideal for many transplant purposes, ranging from bioengineered replacement tissues to genetically engineered cell transplants to cure inherited disorders, and of course stem cells created from cloned adult cells from people with a wide range of diseases can be used to create a huge range of in vitro disease models to improve our understanding of the biological process at work and hasten the development of new therapies.

Of course there is already another technology that allows scientists to reprogram cells to a pluripotent state, in 2006 induced pluripotent stem (iPS) cell technology burst onto the scene and quickly became the methodology of choice for many stem cell researchers, with the first clinical trial in human patients expected to start later this year. Has human therapeutic cloning missed the boat?  In an excellent commentary in Nature News on today’s announcement David Cyranoski points out that there is evidence (from studies comparing  SCNT with iPS cells in mice) that cells produced through SCNT are more completely reprogrammed to an embryonic state than iPS cells. So, it is likely that each technique will have its advantages and disadvantages depending on the goal of the research…and in scientific research it is always a good idea to have more than one horse in the race.

We congratulate Professor Mitalipov and his colleagues at OHSU on another stunning scientific achievement, one that will advance medicine, and no doubt be read about by students for many years to come!

Speaking of Research

(1) Tachibana M. et al. “Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer” Cell, published online 15 May 2013 DOI:10.1016/j.cell.2013.05.006

2) Byrne J.A. et al. “Producing primate embryonic stem cells by somatic cell nuclear transfer.” Nature. 2007 Nov 22;450(7169):497-502. PubMed:18004281

Brain Awareness Week: The Role of Animals in Neuroscience

If you’re a regular reader of the Speaking of Research science blog you will know that we are very interested in neuroscience – in fact several of us are neuroscientists – so you won’t be surprised to learn that we have been following events during Brain Awareness Week (#brainweek on twitter).  Brain Awareness Week is a global campaign to increase public awareness of the progress and benefits of brain research that is organized every year by the Dana Foundation in partnership with over 100 research institutes, medical charities and universities around the world.

We thought it was a good opportunity to see what new resources on the use of animals in brain research are available from key organizations involved in Brain Awareness Week, and BrainFacts.org – a public information initiative whose launch we reported last May – delivered the goods. Brainfacts.org have been busy since we last reviewed their website, and their pages on animal research in neuroscience have grown into an excellent resource that covers a wide variety of topics including how animal research is planned, undertaken and regulated, and case studies of where animal research has made key contributions to advancing neuroscience.  Among the resources are articles written by neuroscientists and excellent videos.

The contribution of animal research to brain research has been highlighted by several recent media reports of important advances in brain science. These have ranged from a study in mice that demonstrated that high salt intake can increase the activity of a class or immune cells known as Th17 cells that have been implicated  in the early development autoimmune disorders such as Multiple Sclerosis, to a study that showed how brain implants could enable rats to sense infra red light with great potential for the development of sensory prosthetics to complement recent advances on the control of robotic limbs, to the identification in rats of a protein that plays a key role in enabling some brain cells to survive following a stroke and may lead to new therapies.

Today there was another great piece of research (1) to report as a team of stem cell researchers at UW Madison led by Professor Su-Chun Zhang  and Professor Marina Emborg chalked up another first, demonstrating for the first time that it is possible to transplant neurons generated using iPS cell techniques from a monkey’s own skin cells into their brain, where they develop into several types of mature brain cell.

GFR labelled neuron. Image courtesy of Yan Liu and Su-Chun Zhang, Waisman Center

GFR labelled neuron. Image courtesy of Yan Liu and Su-Chun Zhang, Waisman Center

The success of this study is enormously promising for the future of personalized stem cell therapies for Parkinson’s disease, stroke and other brain disorders, as the report in the University of Wisconsin Madison News makes clear.

Because the cells were derived from adult cells in each monkey’s skin, the experiment is a proof-of-principle for the concept of personalized medicine, where treatments are designed for each individual.

This neuron, created in the Su-Chun Zhang lab at the University of Wisconsin–Madison, makes dopamine, a neurotransmitter involved in normal movement. The cell originated in an induced pluripotent stem cell, which derive from adult tissues. Similar neurons survived and integrated normally after transplant into monkey brains—as a proof of principle that personalized medicine may one day treat Parkinson’s disease.

And since the skin cells were not “foreign” tissue, there were no signs of immune rejection — potentially a major problem with cell transplants. “When you look at the brain, you cannot tell that it is a graft,” says senior author Su-Chun Zhang, a professor of neuroscience at the University of Wisconsin-Madison. “Structurally the host brain looks like a normal brain; the graft can only be seen under the fluorescent microscope.”

Rhesus macaques play a key role in brain research...

Rhesus macaques play a key role in brain research…

It’s interesting to note that the development of green fluorescent protein (GFP) labelling that played a crucial role in allowing Profs. Zhang and Emborg’s team to distinguish transplanted cells from host cells in the monkey brain was made possible by research in the nematode worm Caenorhabditis elegans , a tiny worm that itself plays a perhaps surprisingly important role neuroscience.

...as do nematode worms!

…as do nematode worms!

These discoveries and advances impact on many areas of brain research, and have the potential to benefit those suffering from a wide variety of brain diseases and injuries, so it is fitting that in Brain Awareness week we salute the researchers whose ingenuity and hard work makes them possible.

Speaking of Research

1) Marina E. Emborg, Yan Liu, Jiajie Xi, Xiaoqing Zhang, Yingnan Yin, Jianfeng Lu, Valerie Joers, Christine Swanson, James E. Holden, Su-Chun Zhang “Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain” Cell Reports, Published online 14 March 2013, DOI: 10.1016/j.celrep.2013.02.016

Safeguarding medical progress means supporting animal transport

The following guest post is from Eric Raemdonck, who has a background in the aviation transport industry. Eric recently launched the Advancing Animal Research blog, whose purpose is to ” establish bridges between the aviation world, the life sciences, health care, pharmaceutical, animal research industries,  educational institutions and their  affiliate or representative associations as well as Governmental organisations”.

Facing a virulent campaign by animal rights activists, a growing number of airlines around the world now refuse to transport certain species of research animals, chiefly non-human primates (NHPs).  This worrisome development not only threatens medical progress, but also puts the health and welfare of those animals at risk.

Animal rights extremists are trying to put a chokehold on the airline industry’s service to biomedical research via social media write-in campaigns, demonstrations at airline offices around the world, and even protests at the homes of airline executives.

Everyone concerned with the future of biomedical research must actively reject these tactics of intimidation and harassment, and stand in support of those airlines that continue to transport animals safely, comfortably and quickly to where they are needed to advance the quest for treatments and cures.

As a former secretary of the International Air Transportation Association’s Live Animals and Perishables Board, I can attest that airlines that transport animals employ highly skilled specialists and focus on finding the quickest routes possible to ensure the health of the animals en route to research institutions.

Animal research remains a small but vital component of the research and development process for new medicines.  Without the ability to move research models from one country to another, or from breeder to research institution, crucial scientific research seeking new treatments for heart disease, cancer, spinal cord injuries, epilepsy and numerous other ills could come to a halt.

As things stand, almost every commercial airline in the world, save but a handful, now refuses to transport non-human primates for research, even though many have policies in place allowing for the transport of NHPs for other purposes.

The United Kingdom has perhaps the most stringent laws and oversight on the use of animals in research, yet no U.K.-based air carrier is willing to transport NHPs destined for research into the country.  In the United States,  very few commercial carriers remain to do the job.  Airlines of other nations, upon which research institutions are increasingly relying for their animal transportation needs, are also feeling the pressure from activists and some have already given way to demands that they no longer carry laboratory animals.

Why is this happening?  Why are airlines targets?

As research institutions themselves become increasingly adept at blunting the impact of activists’ campaigns, leaders in the animal rights movement are now looking toward those companies with whom the research community works or relies upon for services.  ‘Stop research animal transportation and you stop animal research’ is the thinking behind the actions of animal rights extremists in targeting airlines.

Animal extremist campaigns against the airlines, such as the British Union for the Abolition of Vivisection’s Primate Cargo Cruelty and various Internet petitions attract thousands of signatures.   PETA also has an action alert on its web site, calling on readers to “Ask Airlines to Stop Shipping Monkeys to Be Tortured.”

Social media tools such as Facebook, YouTube and Twitter are used extensively in these campaigns to solicit support, donations, and calls for immediate action to change airline policy to include a ‘no-fly’ regulation for research animals.

The message to their followers is clear: only a few airlines remain, and by working together activists can put a stop to this practice.  The message to the airlines is equally clear: change your transportation policy or we will tell the public to no longer fly with you.  Through email campaigns alone,  some lasting only a few hours, several airlines have made the decision to stop transporting research animals.  This was done without any consultation with the companies involved and without  any notice.  This has occurred while airlines continue to transport animals for other industries and passengers.

Straightforward security steps taken by airlines and research institutions alike can blunt the impact of many of the activists’ campaign tactics, and protect the airlines and others involved in the global supply chain. Additionally, there are steps that concerned individuals may take to help ensure that safe and humane transport of laboratory animals will continue.

1/Stand by the airline industry and voice your support through associations such as AALAS – American Association for Laboratory Animal Science (www.aalas.org),   CALAS—Canadian Association for Laboratory Animal Science (www.calas-acsal.org) ICLAS – International Council for Laboratory Animal Science (www.iclas.org) and other scientific and professional organizations that advocate for both biomedical research and laboratory animal welfare.  Ensure that the issue of protecting humane research animal transportation is on their agendas.

2/Ensure that your elected officials appreciate the importance of animal research, and ask them to look into the problem of the declining pool of available airlines for the continued transport of research animals.

3/Inform others as to the humane and judicious nature of animal research, and why it is still needed.  Underscore its achievements and the medical progress to which it has contributed.  Information and links to resources to get you started are here on the Speaking of Research site, and on my Advancing Animal Research blog at http://research4drugdiscovery.blogspot.ca/

Eric Raemdonck

Bridging the gap: Monkey studies shed light on nature, nurture, and how experiences get under the skin

“Is it nature or nurture?”

“How does that work? How can social experiences actually change someone’s brain?”

“So early experiences matter, but how much?  Is it reversible? How long does it last? Is there a way to change the course?”

All of these are popular questions that I hear from students, community members, clinicians, and other scientists when I talk about my research with monkeys.  The nature vs. nurture question is one of high public interest.  It is one that is at the center of our understanding of who we are and how we come to be that way.  And it is a very old question.  Yet it is also one that continues to resonate and become even more intriguing as new discoveries rapidly change what we know about biology and genes, and illuminate with increasing specificity the ways in which nature and nurture together play dynamic roles in shaping the development of each individual.

For example, through research with humans, monkeys, rats, mice and other animals, we know that genes are not only involved in differences between individuals’ behavior, health, and biology, but also that an individual’s social environment and childhood experiences can actually change how genes behave and, in turn, have biological consequences.  In other words, those previous gray areas surrounding exactly how nature and nurture work together are now being filled in with a more specific understanding.

Why does this matter? There are many important reasons. Among them, it is this specific information that allows us to develop better prevention, intervention, and treatment strategies for those negative health outcomes that follow adverse experiences. One example of this can be found in our rapidly advancing knowledge of how brain neurochemistry, which plays a major role in mental health disorders, is affected both by genetic differences between individuals and also by early life experiences. This knowledge provides not only the basis for developing treatments that target the specific neurochemicals involved in a disorder, but also provides important clues for early identification and intervention for those at risk. At the same time, understanding that experiences have long-lasting consequences on biological pathways involved in lifetime health underscores the importance of public policies that work to promote better early environments.

I am one of the many scientists who are devoted to work aimed at better understanding how many different kinds of early experiences can influence a wide range of health outcomes during an individual’s lifespan. My own part of this work primarily includes non-invasive studies with monkeys and focuses on developmental questions about behavior, aspects of brain chemistry and development, and genetics. For example, I use neuroimaging (MRI) to look at how brain development can be affected by early life experiences and we have monkeys play videogames, solve puzzles, and respond to mild challenges so that we can better understand their learning, memory, cognition, and temperament.

Part of my work involves studying how middle-aged monkeys (15+ years old) who were raised in infancy with their mothers differ from monkeys nursery-reared in infancy with their peers. The two groups have the same experiences following the early life period, and during infancy and throughout their lives, both groups are housed in enriched environments with excellent diets, toys, and medical care. Although my current work is focused on a small number of nursery-reared animals, it does not involve creating new animals or a nursery. It depends on healthy animals who have been part of our work for many years and, as with all of our studies, we treat these animals humanely, with careful attention to providing them with healthy diets, environmental enrichment (e.g., a variety of toys, puzzles, fresh fruit and vegetables, and foraging opportunities), and excellent clinical care by veterinarians.  We do this because we care about the animals’ well-being and also because our studies depend upon healthy animals.

Adult rhesus macaque

There are less than a handful of studies concerned with how monkeys’ early rearing influences their behavior and other aspects of health in middle- and older-age. As a result, although we have a strong platform of knowledge about the effects of early life experience in younger animals, we know very little about whether these effects persist into older age, about what systems are affected, and the degree to which individuals vary.

This study, like those of others who study the effect of different early life experiences on a range of health outcomes, is aimed at uncovering the biological basis of a key finding relevant to human health. We know from human studies that a wide range of early experiences, including not only childhood neglect and abuse, but also poverty and other types of adversity, are associated with negative health outcomes later in life. In humans, however, it is impossible to truly disentangle the effects of early adverse life experiences from differences in diet, environment, access to medical care, and other factors that vary across the lifespan. Animal studies allow us to control many of the factors that vary widely in humans and have consequences on health. For example, animals with different early experiences have the same environment and experiences afterwards, including healthy diets and excellent medical care. As a result, when we find significant differences in behavior, brain chemistry, brain structure, and immunology between animals with different early experiences we know that these differences are not due to disparity later in life.

Early experiences do not tell the whole story, however, as we know from the common observation that two individuals who experience the same early environment or challenging experiences, may wind up with very different health pathways.  Part of the obvious reason for this is genetic variation. Understanding how differences in genes contribute, however, and which biological pathways are affected or how permanent those effects may be, are now the real questions that remain to be fully answered. Animal studies provide one of the critical ways to view the interplay and roles of genes, environments, and experiences. This is because, unlike in human studies, animal studies can make use of strong experimental control and mechanistic approaches in order to compare the biological and behavioral responses of individuals who have similar genes and different environments, or individuals with different genes in the same environment.

Another part of my research involves studying how genes affect an individual’s response to the environment and how that occurs at a biological level.  The kinds of questions that we address include:  When two individuals experience the same stress, or the same environment, why are some relatively unaffected (resilient) and others more vulnerable?  What genes play a role in this difference?  What biological systems?  My work, along with that of my colleagues, has demonstrated that genetic factors play a crucial role in how individuals differ in terms of their resilience or vulnerability to early adversity. It is through studies with monkeys that my colleagues and I were able to first identify how interplay between specific genetic variation and early experiences together influence brain chemistry that influences a wide range of behaviors and aspects of health.  This finding in monkeys preceded and spurred subsequent similar studies in humans that continue to show that for most complex traits, genes do not always predict an individual’s destiny; environments have tremendous influence; and understanding individual differences requires consideration of both nature and nurture. As a result, we not only now know more about the genetic and biological underpinnings of individual differences in vulnerability to early life stress, but we also can move forward in identifying the specific ways that this occurs.

In all of these studies, our goal is to produce new understanding about how early experiences affect individuals throughout their lives.  Furthermore, like other biomedical animal research, our goal is to produce information that is relevant to human health and to address questions that are raised by challenges to human health but that cannot be addressed in studies of humans. In other words, aspects of similarity between human and nonhuman primate genetics and biological response to experiences are central to the rationale and success of the research. Studies with monkeys are a small, but important, part of the research aimed at uncovering how early experiences affect health.  As with most areas of research, new understanding and progress depend upon bridges between studies that use different populations (both human and other animal) and that draw from many different areas of expertise. Work in this area has progressed through the efforts of psychologists, neuroscientists, behaviorists, geneticists, molecular biologists, immunologists, physicians, population epidemiologists, sociologists, and others. In other words, the question is of interest from many perspectives and is addressed with interdisciplinary approaches that make it possible to build connections between findings so that the results of basic research can provide useful evidence to inform better health practices, clinical care, and public policy.

Why are these studies and findings important?  In short, because they provide us with a way to better understand the specific biological mechanisms by which early life events affect health.  As a result of decades of research in both humans and other animals, we know some of the specific biological, neural, immunological, and genetic pathways that are affected. These studies have informed progress in our understanding of the importance of early childhood experiences for lifelong health, the biological basis of mental health disorders, and the potential to change health trajectories through early identification of risk and appreciation of individual differences. Through the combined force of basic and clinical studies, we will continue to progress in understanding how genes, experiences, and biology interact. In turn, this understanding will continue to help in pinpointing mechanistic targets and shedding new light on those avenues for prevention, intervention, and treatment that improve human and animal health.

Allyson J. Bennett, Ph.D.

Not Difficult To Grasp

Paralysis can have tremendous negative consequences for a person’s quality of life.  In the US alone, there are more than 200 thousand people living with chronic spinal cord injury, which is a cause of immense suffering to them and their families.  The disease generates economic burden for society as well.   Thus, there has been a lot of interest in using our knowledge of how movement is coded in the brain to allow patients to bypass nerve injuries and communicate directly with the environment.  Moreover, when asked about their priorities in terms of regaining motor function the vast majority of patients rank regaining arm and hand function as most important.

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.

Tom talks nerdy to Cara Santa Maria about monkeys, prosthetic hands and brain machine interfaces.

Speaking of Research founder Tom Holder was  recently interviewed by the Huffington Post’s new science correspondent Cara Santa Maria for her blog “Talk Nerdy To Me” .

In her latest post Cara examines whether research performed on monkeys by a Chinese group with the aim of developing improved brain-machine interface technology to control a prosthetic hand is justifiable.

It is worth noting that in addition to preventing the monkey from pulling the wires out of the electrodes by accident, the restraint chairs – in which the monkeys are only kept for short periods – also prevent the monkey from simply reaching out and grabbing the juice, obliging it to use its brain instead.

This is field of research we have discussed on several occasions since Speaking of Research was founded, most recently in a post last October when we took a look at a successful early clinical trial of a brain machine interface developed through research in monkeys by scientists at the University of Pittsburgh, which allowed a paralyzed man to control a robotic arm.

We also discussed research being undertaken at Duke University , where scientists are developing a system that they hope will allow patients to feel what their prosthetic limb is touching, allowing for much finer control and dexterity. The electrodes implanted in the brains of the human patients are essentially the same as those used in the monkey studies, and they are painless once implanted, and are implanted under anesthesia – general anesthesia for monkeys but usually local anesthetic  for humans (so the patient can help position the implant).

STOP lying about research at the University of British Columbia

In a post a couple of weeks ago entitled “End of primate research at the University of Toronto?” Allyson Bennet wrote about the truth behind the spin that primate research has ceased at the University of Toronto (UT), commenting that:

 If nothing else, those inclined to dodge should consider that they are deriving benefit from the work of their colleagues at the institutions still willing to assume the risk and responsibility.”

It hasn’t taken very long for other animal rights groups in Canada to pick up on UT’s perceived change of policy, with a Vancouver-based group named STOP UBC Animal Research (STOP) quick to demand that the University of British Columbia (UBC) follow UT’s example.

For more than a year now STOP have been engaged in a high-profile campaign against animal research at UBC, prompting UPC to respond by providing information about the animal research they undertake. One of their main targets has been Professor Doris Doudet, who employs advanced imaging modalities such as positron emission tomography (PET) for the evaluation of functional, neurochemical, and anatomical changes in the brains of animal models of Parkinson’s disease.

In a paper published online last November in the Journal of Cerebral Blood Flow and Metabolism Professor Doudet and her colleagues reported that they had used PET to confirm that abnormal metabolic patterns recently observed in the brains of Parkinson’s disease patients are also found in the brains of monkeys which have been treated with the drug MPTP to kill the dopamine producing neurons in the brain and induce Parkinsonism. This result both confirmed the close similarity between MPTP-induced Parkinsonism and Parkinson’s disease, and provides another useful way in which the effects of candidate therapies for the treatment of Parkinson’s disease can be evaluated in this much-used animal model of Parkinson’s disease.

Unfortunately in the course of the experiment four of the eleven monkeys treated with MPTP developed an unusually severe response, and rather than recovering after the experiment – as is usually the case with monkeys treated with MPTP – they had to be euthanized. The Journal of Cerebral Blood Flow and metabolism paper makes it clear that Prof. Doudet and her team responded quickly and correctly to the unexpected situation to minimize any suffering the animal’s experienced.

Not surprisingly STOP are seeking to make capital out of this event…but this is where animal rights propaganda parts company with the facts.

In a statement to the UBC student newspaper Ubyssey STOP claim that far from being accidental the four monkey deaths were planned:

a 2010 progress report on Doudet’s study indicated four monkeys were to be “sacrificed to neuropathology”—two at the six-month mark after showing mild symptoms of Parkinson’s, and the final two after twelve months.

“Animals should be able to recover from the Parkinsonism that researchers inflict on them,” Birthistle said. “She’s intending to kill them all along, and then they’re talking about it as being unforeseen circumstances.””

So what is this “2010 progress report? Well, another statement by STOP quoted in a Vancouver newspaper explains that they are referring to a study named “L91”.

So what is L91 all about?

It’s not the first time that STOP have complained about study L91, back in January of last year they staged a protest against it. L91 is a project planned by Prof. Doudet to use PET to study the effect of injection of the proteasome-inhibitor Lactacystin on the brain function of four macaques, and a description of the proposed project can be found on page 25 of this TRIUMF publication. Lactacystin injection is a relatively new animal model of Parkinson’s disease, recreating the damage to the proteasomes of the dopamine secreting neurons of the substantia nigra region of the brain observed in Parkinson’s disease patients, and has the potential to become a valuable resource for evaluation new therapies.

So it’s abundantly clear that the proposed study L91 is NOT the same as the study published last November in the The Journal of Cerebral Blood Flow and Metabolism, as the former plans to use lactacystin to induce Parkinsonism while the latter used MPTP. It is equally clear that STOP are well aware that these are not the same study, as they have access to all the relevant documents.

Yet, not only to STOP repeatedly and dishonestly claim that these are the same study, but on the basis of this claim they go on to make false allegations of professional misconduct against Prof. Doudet and demand that UBC suspend her from her duties and carry out a full investigation.

And I’ll bet that they will express surprise and outrage when UBC refuses to comply with their demands!

Before leaving this subject it’s worth addressing the importance of the role of animal research in Parkinson’s disease research, something that we are well aware of thanks to Pro-Test’s own Prof. Tipu Aziz, whose research using the MPTP model of Parkinsonism made major contributions to making deep brain stimulation (DBS) for Parkinson’s disease the success it is today.  I’ll value the views of the neuroscience community as a whole – including great neuroscientists such as the physician-scientist Prof. Alim-Louis Benabid, pioneer of DBS for Parkinson’s disease – over those of the few fringe scientists that STOP can scrape together.  Prof. Benabid and other genuine experts on Parkinson’s disease recognize that while Parkinsonism models such as the MPTP monkey do not recreate every aspect of Parkinson’s disease they play a vital role alongside clinical research in uncovering the process that cause the disease and its symptoms, and in the development of new therapies for Parkinson’s disease.

As Prof. Benabid wrote in a review in 2004:

The knowledge of the functional changes of basal ganglia activity in the parkinsonian state as it emerged from extensive experimental studies on animal models has provided the theoretical basis for surgical therapy in PD. The 6-hydroxydopamine (6-ODHA) rat model and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of PD provided powerful research tools for uncovering the pathophysiology of changes in functional basal ganglia activity in PD. “

and in a review published this year

The specific effect of DBS at high frequency, discovered during a VIM thalamotomy, was extended to the older targets of ablative neurosurgery such as the pallidum, for tremor in Parkinson’s disease (PD), dyskinesias, essential tremor, as well as the internal capsule to treat psychiatric disorders (OCD). A second wave of targets came from basic research (in this instance animal research –PB), enabled by the low morbidity, reversibility, and adaptability of DBS. This was the case for the subthalamic nucleus (STN) which improves the triad of dopaminergic symptoms, and the pedunculopontine nucleus (PPN) for gait disorders in PD. “

As with so many areas on medicine it is the confluence of animal and clinical researhc that is driving advances in the treatment of Parkinson’s disease.

Rather ironically animal rights organizations like STOP and their supporters are very quick to claim that Prof. Benabid’s serendipitous discovery that electrical stimulation of the ventralis intermedius could reduce the tremor associated with Parkinson’s disease demonstrates that research using the MPTP model is unnecessary. They seek to co-opt his stature as a leading neuroscientist while simultaneously ignoring the fact that he not only recognizes the importance of animal models of Parkinson’s disease but himself undertakes studies with the MPTP Monkey model and other animal models of Parkinson’s disease.

So, the question is who you are going to believe, leading neuroscientists like Prof. Doudet and Prof. Benabid, or STOP? Somehow I doubt it will take you long to come to a decision!

Paul Browne