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Do Politics Trump Chimpanzee Well-being? Questions Raised About Deaths of US Research Chimpanzees at Federally-Funded Sanctuary

A number of countries have ended some types of research with chimpanzees over the past decades.  For example, the US National Institutes of Health announced in November 2015 that it would no longer support many types of chimpanzee research. In Europe, the fate of former research chimpanzees has depended upon a mix of private wildlife parks and zoos for the animals’ care and management. The outcomes in term of chimpanzee health and survival remain relatively unknown.

Photo credit: Kathy West

Photo credit: Kathy West

In the US, the American public, via public entities, has legislated long-term support and substantial funding for the construction and maintenance of a facility dedicated to the exclusive care of chimpanzees retired from research. However, the outcomes for retired chimpanzees have been the source of public discussion and increasing concern.

This month, Dr. Cindy Buckmaster, writing in Lab Animal (Vol 45, No 7, July 2016) in an article addressed to the National Institutes of Health Director and titled: “Dr. Collins, please save our chimps!” shared a powerful and very sad story about some of the chimpanzees, asking:

“…why Dr. Collins would force these animals to leave everything they have known and everyone they love to go to a strange place, filled with strangers who cannot care for them nearly as well as their family at MDAKC! Does he know that 69% (9 out of 13) of the chimps already moved from MDAKC to his chosen sanctuary have died? Does he know that most of these treasured family members died within a few months of their arrival at the sanctuary? Does he know how they suffered? Does he know their stories? What about Maynard, who had ‘the best play face and laugh ever,’ and loved playing with his human and animal family at MDAKC? Does Dr. Collins know that Maynard had a fatal heart attack in the sanctuary the day after he was introduced to a new group of chimpan­zees? Does he care? I’d like to believe that he does, but I don’t know him. If I did, I would ask him to visit the MDAKC chimps so he would know, beyond doubt, that retirement in place is the most loving thing he could do for these animals. And I would beg him to save our chimps.”

maynard

Photo credit: Kathy West

labanjulyBuckmaster’s plea echoes those of others with concern that unrelenting political pressure on the NIH from groups opposed to animal research has resulted in decisions about chimpanzees that may not be in the animals’ best interests. In the aftermath of a series of decisions by the NIH over the past several years and increasing pressure by opponents of animal research, NIH has mandated the transfer of chimpanzees from their homes, established social groups, and dedicated caregivers to the Louisiana facility (See: Where should US chimpanzees live; Chimpanzee retirement: facts, myths and motivations; and What cost savings: a closer look a GAPCSA 2011).

The result of the transfers has included injuries to chimpanzees as they are introduced into new social groups and to deaths of animals. As Buckmaster notes, for one recent group of 13 relocated chimpanzees, the result was a nearly 70% death rate for animals moved from dedicated research facilities with long-time experience in caring for the animals to the Louisiana sanctuary. As a result of a decades-old ban on breeding, all sanctuaries and research facilities housing chimpanzees are largely populated by aging animals. Yet, the number of chimpanzees that have died upon transfer from research facility to sanctuary contrasts with an average death rate for chimpanzees due to advanced age, health, or other causes for a given facility, an expected average of  3-4 individuals per year (http://www.gao.gov/products/GAO-16-392).

Bastrop chimps tool useResearch chimpanzees make up approximately 40% of the 1,650 chimpanzees estimated to live in the US, which includes chimpanzees not only in research facilities, but also sanctuaries, zoos, and other entertainment and breeding venues (see graph below). As recently announced, a large number of research chimpanzees housed at the New Iberia Research Center will retire to a private US sanctuary in northern Georgia.  The remaining US research chimpanzees are under 1/3rd of all chimpanzees housed in the US.

where us chimpanzees live 07.13.16

The chimpanzee deaths at Chimp Haven have increasingly raised significant questions in the communities that are concerned with ape well-being These concerns are the subject of considerable private discussion in the chimpanzee research community by those who have cared for the animals for decades. Public expressions of concern have been more constrained, but are emerging, as are calls for a re-examination of where the chimpanzees should live. For example, Buckmaster says:

“In fact, many of our chimps would fare better if they were allowed to retire in place. And several of these precious creatures have already suffered and died because the NIH would not allow them to do so. The MD Anderson Keeling Center (MDAKC) in Texas has been home to the healthiest, happiest chimpanzees in America for decades. Their living quarters are comparable to, or better, than any US sanctuary, and none of these sanctuaries can compete with the level of care provided to chimpanzees at MDAKC. The MDAKC staff includes ten full-time veterinarians with a combined total of 92 years of experience caring for chimpanzees; 6 are specially boarded primate veterinarians, 3 are specially boarded veterinary pathologists, and 3 are specially certified to provide laser and acupuncture therapies to supplement traditional treatment regimens. There are also 22 specially trained, full-time technicians devoted to the chimps’ husbandry, health and behavioral needs, including 3 night technicians. MDAKC also has a full-service clinical pathology laboratory on site that allows for the immediate diagnosis and treatment of animals with health concerns. No US sanctuary is staffed or equipped to care for chimpanzees like MDAKC, not one! In fact, the sanctuary that the NIH is forcing us to send our chimpanzees to currently is not even equipped to carry out its own diagnostic lab work. This is concerning, given the advanced age of many research chimpanzees. Honestly, it would make more sense for Dr. Collins to retire the nation’s research chimps to MDAKC! 

Buckmaster’s comments should resonate with all of those concerned with ape well-being. The US public has provided considerable support meant to give these chimpanzees retirement care—on the assumption that such care would be in the animals’ best interests and protective of their health and well-being in retirement. The federal commitment to ape retirement is unusual compared to other countries.It also reflects broad support from the research community as well as the public.

Chimp Haven, the first and only federal chimpanzee sanctuary in the US, was founded in 1995 by a NIH-funded behavioral scientist Dr. Linda Brent along with a group of primatologists and business professionals. Through federal legislation in 2000—the Chimpanzees Health Improvement, Maintenance, and Protection Act (CHIMP Act; 42 U.S.C. §§ 287a-3a)—a national chimpanzee sanctuary system was established and NIH was formally mandated to provide life-time funding for the research chimpanzees it retires. As a result, in 2002 the NIH awarded Chimp Haven a 10-year, cost-sharing contract in which the NIH provided roughly $19 million in total costs for retired chimpanzee care, as well as $11.5 million for initial construction of the sanctuary. Six years later, in 2008, federal sanctuary standards were established (see Fed. Register 73 FR 60423, Oct. 10, 2008: Standards of Care for Chimpanzees Held in the Federally Supported Chimpanzee System). These standards apply to Chimp Haven, but do not necessarily extend to other sanctuaries.

CC-BY-NC-SAThus far, the federal investment in sanctuary retirement exceeds $30M. An analysis by the Congressional Budget Office (CBO) in 2012 estimated an additional $56M cost to retire and maintain federally-funded chimpanzees for a 5 year period (not the animals’ lifespan). A 2016 Government Accounting Office report determined that the range of per day care costs paid by NIH for a chimpanzee housed in the four facilities NIH supports was between a low of $41 and a high of $61, or between $15,000 – $22,000 per chimpanzee per year. Thus, NIH’s total support for care and maintenance of its 561 chimpanzees each year may be between $8,415,000 – $12,342,000.  By extension, over a 5 year period, the cost would be between $42,075,000 – $61,710,000. NIH pays 75% of costs and Chimp Haven is required to provide matching funds via private donations and fundraising. Of critical note, the cost for chimpanzee care will also likely vary significantly with increasing medical and care needs as the population ages.

http://www.gao.gov/products/GAO-16-392In light of a complex mix of animal welfare, cost, and pragmatic concerns, a substantial number of NIH-owned research chimpanzees have not yet been transferred to Chimp Haven. The speed of transferring NIH-owned chimpanzees to sanctuaries remains a source of contention and was directly addressed by the 2016 GAO report. The report determined that: “Most of the 561 chimpanzees that NIH owned or supported as of January 15, 2016, had not been retired to Chimp Haven, which housed 179 NIH-owned chimpanzees at that time.” The agency concludes that NIH “has not developed or communicated a clear implementation plan to transfer the remaining chimpanzees, in part because of uncertainties about the available space at Chimp Haven. However, NIH has information about Chimp Haven’s current capacity and about anticipated space that will become available as a result of chimpanzee mortality. Absent a clear implementation plan, the four facilities that care for NIH-owned or NIH-supported chimpanzees may not have the information they need to care for the chimpanzees in the most cost-effective way that considers the timing of the transfers and the welfare needs of the chimpanzees. … Moreover, the absence of such a plan is inconsistent with federal internal control standards that call for effective communication of quality information.”

At the same time, active public discussions are continuing about whether NIH-owned chimpanzees should be retired in their current settings (in situ retirement), or if substantial funds for new construction should be made available in order to provide for their transfer to the federal sanctuary. Among the arguments for retiring the chimpanzees in their current homes is that the research facilities can offer the same level of care as the federal sanctuary, particularly given the new requirement for ethologically-relevant standards of care. From the animal welfare perspective, retirement in place would also have the advantage of protecting the chimpanzees—many of whom are aged— from the stress of relocation and disruption of stable social groups. For example, in an earlier interview about movement of chimpanzees, veterinarian and director of the MD Anderson Keeling Center for Comparative Medicine, Dr. Christian Abee:

“praised Chimp Haven’s facilities, but he said the stress of moving can take a fatal toll on older, more frail chimpanzees. Of the 13 chimps his facility had transferred this year to Chimp Haven, four died or were euthanized within the first three months, he said. Chimpanzees, an endangered species native to West and Central Africa, can live to 60 years in captivity. I don’t mean this as a criticism of Chimp Haven, but we uprooted them, took them from their family groups, we moved them cross country, we put them in unfamiliar settings with caregivers who didn’t know them, and four died,” Abee said. “We would not have anticipated those four to die if they had stayed here” (Walters & Knowles, 2015).

CC-BY-NC-SAFrom the perspective of the individual animal’s health and well-being, the type of facility in which he or she lives is only relevant insofar as it affects the provision, stability, and type of care, housing, and other aspects of daily life. In other words, whether the facility is a sanctuary, zoo, or research institute may be irrelevant if the standards for care, housing, and living conditions are substantively similar across settings. Ultimately, from the available data and the chimpanzee deaths that have occurred following their relocation to the federal sanctuary, it may appear that NIH and others advocating for transfer of the animals from their current homes and social groups to the sanctuary may be making a mistake. It is a mistake that is counterproductive to the animals’ welfare. It is one that appears to prioritize political considerations and appeasement of opponents of animal research over the interests of the animals themselves. In short, political expediency seems to be trumping animal welfare for chimpanzees and this serves no one well.

Speaking of Research

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Portions of this post are excerpted from Bennett, A.J. & Panicker, S. (in press). Broader Impacts: International Implications and Integrative Ethical Consideration of Policy Decisions about US Chimpanzee Research. Am J Primatology.

Zika research in nonhuman primates critical as fears among pregnant women, families grow

Jordana Lenon, B.S., B.A., is the outreach specialist for the Wisconsin National Primate Research Center and the Stem Cell & Regenerative Medicine Center, both at the University of Wisconsin-Madison. In this guest post Jordana talks about WNPRC research on Zika virus.

Wisconsin National Primate Research Center scientist David O’Connor is emphasizing using “as few animals as possible” to answer research questions that desperately need answers as the world watches Zika virus cause birth defects and raise fears among pregnant women and their families across the warmer Americas. These answers, O’Connor expects, will move him and his collaborators at the University of Wisconsin-Madison, Duke University, in Brazil and beyond forward as they learn more each day how Zika virus may be operating inside of infected pregnant women and their newborns, and could cause potential lifelong impairments we don’t even know about yet.

Researchers at the Wisconsin National Primate Research Center perform a fetal ultrasound on a pregnant rhesus macaque, in their quest to learn more about the link between the Zika virus and birth defects. (Images by Justin Bomberg, UW-Madison Communications)

Thanks to research using rhesus macaques, whose immune, reproductive and neurological systems are very similar to ours, the answers are starting to come in. Furthermore, O’Connor and his Zika Experimental Science Team, or “ZEST are sharing their raw research data through an online portal with the public – including of course and very importantly other Zika researchers. Their goal is to share data openly, to eliminate as many impediments as possible to spurring collaborative work around the globe to solve the Zika crisis.

David O'Connor, professor in the Department of Pathology and Laboratory Medicine at the University of Wisconsin-Madison, is pictured on April 19, 2016. (Photo by Bryce Richter / UW-Madison)

David O’Connor, professor in the Department of Pathology and Laboratory Medicine at the University of Wisconsin-Madison, is pictured on April 19, 2016. (Photo by Bryce Richter / UW-Madison)

Just how severe a problem are we looking at? O’Connor gave some perspective during a public lecture on the UW-Madison campus this week. While HIV – another pandemic virus he has studied exhaustively over the past 20 years – costs society about $400,000 per patient over their life spans, Zika virus impairments in newborns could cost between $1-10 million per patient (using US dollar estimates) over their life spans. Recent studies in macaques found that the Zika virus persisted for up to 70 days in the blood of pregnant female monkeys – much longer than the 10 days it remained in either males or non-pregnant females – this increases the chance of severe birth defects being found in babies.

There are already more than 300 pregnant women in the US with laboratory evidence of Zika. This number is growing daily. Infections in the US are largely being attributed to pregnant women picking up the virus while traveling outside the country: Zika is hitting hard right now in Puerto Rico, infecting nearly 50 pregnant women per day, as Aedes aegypti mosquitos, which can transmit viruses such as dengue and Zika, spread and move northward this summer from South to Central America, to the Caribbean and into the United States. Because Zika is also sexually transmitted, its borders of infection are not limited to places where the mosquitos live and bite.

Mother and infant rhesus monkeysThere is hope, however. A new experimental vaccine has shown to protect mice with just a single dose. Scientists from Walter Reed Army Institute of Research, the Beth Israel Deconess Medical Center and Harvard Medical School found two different vaccines effectively protected 100% of mice from the virus. This compares to a control group which were unprotected and all caught Zika after being exposed to the virus.

Jordana Lenon

See the team’s latest research updates on the ZEST web portal site.

View the Wednesday Night at the Lab lecture on Zika virus that Dr. O’Connor gave July 6 on the UW-Madison campus, including his responses to several questions about the virus, immunity, pregnancy, and vaccine development.

Santa Cruz Biotechnology and the USDA

Speaking of Research have been troubled by the events which have unfolded at Santa Cruz Biotechnology (SCBT), including (but not limited to) the recent actions taken against the organization by the USDA. As an organization that strongly supports and advocates for the humane and responsible treatment of laboratory animals, Speaking of Research is critical of any organisation that does not meet its obligation to ensure the welfare of its animals, as well as any efforts to subvert the regulatory process. If the allegations against SCBT are true, their conduct is reprehensible. SR has written about these allegations in the past in the article’s “Santa Cruz Biotechnology: Dealing with Bad Behaviour” and “Caveat Emptor“. The following article is reprinted, with permission, from the American Physiology Society (images are not from the original article).

On May 19, 2016, antibody producer Santa Cruz Biotechnology (SCBT), Inc. reached an agreement with the USDA to resolve allegations of numerous Animal Welfare Act (AWA) violations. Under the terms of this agreement, SCBT neither admitted nor denied wrongdoing. Nevertheless, the company agreed that by May 31, 2016 it would pay a record $3.5 million fine. SCBT also agreed that as of May 31, 2016, it would cease antibody production involving USDA-regulated species and relinquish its registration as a research facility. SCBT also agreed to allow USDA to revoke its license as a dealer as of December 31, 2016, after which it can no longer sell antibodies made from USDA-regulated species.

Photo credit: Dan Coyro -- Santa Cruz Sentinel

Photo credit: Dan Coyro — Santa Cruz Sentinel

USDA filed three formal complaints against SCBT between July 12, 2012 and August 7, 2015 based upon the observations of inspectors from the agency’s Animal and Plant Health Inspection Service (APHIS) during multiple unannounced visits. The USDA complaints alleged that the company repeatedly violated the AWA in its treatment of goats used for antibody production. (For more about the USDA’s case against SCBT, see Caveat Emptor.) The complaints included allegations that SCBT failed to provide appropriate veterinary care to sick and injured animals; that its staff handled animals improperly; and that the company’s institutional animal care and use committee failed to ensure that animals were housed under appropriate conditions and that the animals’ pain and distress were minimized during antibody production. In its third complaint dated August 7, 2015, USDA also alleged that SCBT “demonstrated bad faith by misleading APHIS personnel about the existence of an undisclosed location where respondent housed regulated animals.” This “undisclosed location” was a barn where some 841 goats—including sick ones—were housed.

Top antibody suppliers in the US in 2012. Image from The Scientist

Top antibody suppliers in the US in 2012. Image from The Scientist

SCBT initially contested the USDA’s allegations and sought a hearing before an administrative law judge. After several delays, a hearing where both sides could present evidence case took place August 18–20, 2015 before Administrative Law Judge Janice Bullard. The hearing was suspended on the morning of August 21 with no explanation given. It was later scheduled to resume on April 5, 2016 and then postponed again until August 15, 2016.

The settlement agreement gives SCBT until the end of 2016—when its license will be revoked—to sell antibodies made from blood and serum it collected from regulated animals prior to August 21, 2015. However, SCBT had to stop producing antibodies from this blood and serum by May 31, 2016 when it agreed to cancel its registration as a research facility. Since the AWA does not regulate rodents bred for research, SCBT can continue to sell antibodies produced in mice.

Antibodies play an important role in both clinical medicine and research because they react to the presence of specific proteins. Antibody production starts by injecting an animal with a protein. This activates the immune system, which generates antibodies to identify the invading protein. Some types of antibodies are purified directly from blood collected from animals injected with a protein. Other types can be produced in a laboratory with cell lines created by fusing an initial batch of purified antibodies to harmless cancer cells. Antibodies target either one region of a protein (monoclonal antibodies) or several regions (polyclonal antibodies).

Why did the SCBT case take almost four years to settle? From a legal perspective, APHIS inspections findings represent allegations of AWA violations, and our system guarantees due process: Those accused of violating the law are entitled to their day in court. Kudos should go to USDA for its persistence in marshaling sufficient evidence to convince SCBT to agree to this settlement.

American Physiological Society

USDA publishes 2015 Animal Research Statistics

Congratulations to the USDA/APHIS for getting ahead of the curve for a second time and making the US the first country to publish its 2015 animal research statistics. Overall, the number of animals (covered by the Animal Welfare Act) used in research fell 8% from 834,453 (2014) to 767,622 (2015).

These statistics do not include all animals as most mice, rats, and fish are not covered by the Animal Welfare Act – though they are still covered by other regulations that protect animal welfare. We also have not included the 136,525 animals which were kept in research facilities in 2015 but were not involved in any research studies.

USDA Statistics_2016_A

The statistics show that 53% of research is on guinea pigs, hamsters and rabbits, while 11% is on dogs or cats and 8% on non-human primates. In the UK, where mice, rats, fish and birds are counted in the annual statistics, over 97% of research is on rodents, birds and fish. Across the EU, which measures animal use slightly differently, 93% of research is on species not counted under the Animal Welfare Act (AWA). If similar proportions were applied the US, the total number of vertebrates used in research in the US would be between 11 and 25 million, however there are no statistics to confirm this.

USDA Statistics_2016_B

If we look at the changes between the 2014 and 2015 statistics we can see a drop in the number of studies in hamsters, rabbits, cats and the “all other animals” category. Notably, there was a 7.3% rise in the number of non-human primates used although this comes the year after a 9.9% fall in their numbers.

USDA Statistics_2016_C

There has been a downward trend in the number of AWA-covered animals used in the last three decades, with a 64% drop in numbers between 1985 and 2015. It is also likely that, similar to the UK, a move towards using more genetically altered mice and fish has reduced the numbers of other AWA-covered species of animals used. In the UK this change in the species of animals studied has contributed to an overall increase in the numbers of animals used in research in the past 15 years.

Rises and falls in the number of animals used reflects many factors including the level of biomedical activity in a country, trending areas of research, changes to legislations at home and abroad, outsourcing research to and from other countries, and new technologies (which may either replace animal studies or create reasons for new animal experiments).

It is important to note that the number of animals cannot be tallied across years to get an accurate measure of total number of animals. This is because animals in longitudinal studies are counted each year. Thus, if the same 10 animals are in a research facility for 10 years, they would appear in the stats of each year – adding these numbers would incorrectly create the illusion of 100 animals being used.

Speaking of Research welcomes the open publication of these animal research statistics as offering the public a clear idea of what animal research goes on in their country.

We mightn’t like it, but there are ethical reasons to use animals in medical research

Trichur Vidyasagar, University of Melbourne

The media regularly report impressive medical advances. However, in most cases, there is a reluctance by scientists, the universities, or research institutions they work for, and the media to mention animals used in that research, let alone non-human primates. Such omission misleads the public and works against long-term sustainability of a very important means of advancing knowledge about health and disease.

Consider the recent report by Ali Rezai and colleagues, in the journal Nature, of a patient with quadriplegia who was able to use his hands by just thinking about the action. The signals in the brain recorded by implanted electrodes were analysed and fed into the muscles of the arm to activate the hand directly.

When journalists report on such bionic devices, rarely is there mention of the decades of research using macaques that eventually made these early brain-machine interfaces a reality for human patients. The public is shielded from this fact, thereby lending false credence to claims by animal rights groups that medical breakthroughs come from human trials with animal experiments playing no part.

Development of such brain-machine interfaces requires detailed understanding of how the primate brain processes information and many experiments on macaques using different interfaces and computing algorithms. Human ethics committees will not let you try this on a patient until such animal research is done.

Image: Understanding Animal Research

Image: Understanding Animal Research

 

These devices are still not perfect and our understanding of brain function at a neuronal level needs more sophistication. In some cases, the macaque neural circuitry one discovers may not quite match the human’s, but usually it is as close as we can get to the human scenario, needing further fine-tuning in direct human trials. However, to eliminate all animal research and try everything out on humans without much inkling of their effects is dangerous and therefore highly unethical.

The technique Dr Rezai’s team used on human patients draws heavily upon work done on monkeys by many groups. This can be seen by looking at the paper and the references it cites.

Another case in point is the technique of deep brain stimulation using implanted electrodes, which is becoming an effective means of treating symptoms in many Parkinson’s patients. This is now possible largely due to the decades of work on macaques to understand in detail the complex circuitry involved in motor control. Macaques continue to be used to refine deep brain stimulation in humans.

Ethical choices

The number of monkeys used for such long-term neuroscience experiments is relatively small, with just two used in the study above. Many more are used for understanding disease processes and developing treatment methods or vaccines in the case of infectious diseases such as malaria, Ebola, HIV/AIDS, tuberculosis and Zika.

Approximately 60,000 monkeys are used for experiments for all purposes each year in the United States, Europe and Australia.

However, if one looks at what is at stake without these experiments on non-human primates, one must acknowledge a stark reality. In many cases, the situation is similar to that which once existed with polio. Nearly 100,000 monkeys were used in the 1950s to develop the polio vaccine. Before that, millions of people worldwide, mostly children, were infected with polio every year. Around 10% died and many were left crippled.

Now, thanks to the vaccine, polio is almost eradicated.

Similarly, about 200 million people contract malaria every year, of whom 600,000 (75% being children) die, despite all efforts to control the mosquitoes that transmit the disease. Development of a vaccine is our best chance, but again primates are necessary for this, as other species are not similarly susceptible to the parasitic infection.

Circumstances are similar with other devastating ailments such as Ebola, HIV and Zika. The ethical choice is often between using a few hundred monkeys or condemning thousands or more humans to suffer or die from each one of these diseases year after year.

image-20160505-19765-sm1aov

Reports of medical breakthroughs conveniently leave out animals used in the process.
Novartis AG/Flickr, CC BY

In the popular press and in protests against primate research, there is sometimes no distinction made between great apes (chimpanzees, bonobos and gorillas) and monkeys such as macaques, leading to misplaced emotional reactions. To my knowledge, invasive experiments on great apes are not done anywhere, because of the recognition of their cognitive proximity to humans.

While the ape and human lineages separated six million years ago, there is an additional 20 to 35 million years of evolutionary distance from monkeys, which clearly lack the sophisticated cognitive capacities of the apes.

With urgent medical issues of today such as HIV, Ebola, malaria, Zika, diabetes and neurological conditions such as stroke and Parkinson’s disease, monkeys are adequate to study the basic physiology and pathology and to develop treatment methods. There is nothing extra to be gained from studying apes.

Alternatives have limitations

Opponents of animal research often cite the impressive developments of computer modelling, in-vitro techniques and non-invasive experiments in humans as alternatives to animal experiments. These have indeed given us great insights and are frequently used also by the very same scientists who use animals.

However, there are still critical areas where animal experimentation will be required for a long time to come.

Modelling can be done only on data already obtained and therefore can only build upon the hypotheses such data supported. The modelling also needs validation by going back to the lab to know whether the model’s predictions are correct.

Real science cannot work in a virtual world. It is the synergy between computation and real experiments that advances computational research.

In-vitro studies on isolated cells from a cell line cultured in the lab or directly taken from an animal are useful alternatives. This approach is widely used in medical research. However, these cells are not the same as the complex system provided by the whole animal. Unless one delves into the physiology and pathology of various body functions and tries to understand how they relate to each other and to the environment, any insights gained from studying single cells in in-vitro systems will be limited.

Though many studies can be done non-invasively on humans and we have indeed gained much knowledge on various questions, invasive experiments on animals are necessary. In many human experiments we can study the input to the system and the output, but we are fairly limited in understanding what goes on in between. For example, interactions between diet, the microbiome, the digestive system and disease are so complex that important relationships that have to be understood to advance therapy can only be worked out in animal models.

Of course, animals are not perfect models for the human body. They can never be. Species evolve and change.

However, many parts of our bodies have remained the same over millions of years of evolution. In fact, much of our basic knowledge about how impulses are transmitted along a nerve fibre has come from studying the squid, but our understanding also gets gradually modified by more recent experiments in mammals.

Higher cognitive functions and the complex operations of the motor system have to be studied in mammals. For a small number of these studies, nothing less than a non-human primate is adequate.

The choice of species for every experiment is usually carefully considered by investigators, funding bodies and ethics committees, from both ethical and scientific viewpoints. That is why the use of non-human primates is usually a small percentage of all animals used for research. In the state of Victoria, this constitutes only 0.02%.

Medical history can vouch for the fact that the benefits from undertaking animal experiments are worth the effort in the long run and that such experimentation is sometimes the only ethical choice. Taken overall, the principle of least harm should and does prevail. There may come a day when non-invasive experiments in humans may be able to tell us almost everything that animal experiments do today, but that is probably still a long way off.

Priorities in animal use

The ethical pressure put on research seems to be in stark contrast to that on the food industry. It is hypocritical for a society to contemplate seriously restricting the use of the relatively small number of animals for research that could save lives when far more animals are allowed to be slaughtered just to satisfy the palate. This is despite meat being a health and environmental concern.

To put this in perspective, for every animal used in research (mostly mice, fish and rats), approximately 2,000 animals are used for food, with actual numbers varying between countries and the organisations that collect the data.

The ratio becomes even more dramatic when you consider the use of non-human primates alone. In Victoria, for every monkey used in research, more than one million animals are used for meat production. However, the monitoring of the welfare of farm animals is not in any way comparable to that which experimental animals receive.

Reduced use of livestock can greatly reduce mankind’s ecological footprint and also improve our health. This is an ethical, health and environmental imperative. Animal experiments, including some on non-human primates, are also an ethical and medical imperative.

Trichur Vidyasagar, Professor, Department of Optometry and Vision Sciences and Melbourne Neuroscience Institute, University of Melbourne

This article was originally published on The Conversation. Read the original article.

Herding Hemmingway’s Cats: Book review

What can cats with six toes, flies with wimpy testis, fish with hips, and mice with socks tell us about how our genes work? Turns out, they – together with a cast of characters ranging from bacteria to our own species – can tell us quite a lot.

In Herding Hemmingway’s Cats: Understanding how our genes work Dr Kat Arney takes the reader on a journey through the past and present of the science of genetics, exploring the key discoveries and concepts that are beginning to explain the complex processes through which the hereditary information in our genes constructs us “in all our wobbly, unique and mysterious glory”.

Can this cat be herded? Image: Marc Averette

Can this cat be herded? Image: Marc Averette

It’s a somewhat daunting challenge for a book that weighs in at just over 250 pages, but Dr Arney succeeds with a book that is accessible and entertaining without ever taking its subject for granted. This is in no small way due to the structure of the book, which unfolds in a series of interviews with pioneering scientists – some of whom have Nobel prizes, others who most surely will – whose work has uncovered many different ways in which our genes end up making stuff we need when and where we need it (mostly). Amid the details of their discoveries about phenomena such as junk DNA, gene splicing, imprinting, and RNA interference there are many fascinating glimpses into their personalities, motivations, and occasionally rivalries.

HerdingHemmingway'sCats

For all that Herding Hemmingway’s Cats provides an insight into the tremendous progress that science has made in understanding how genes are controlled, anyone looking for a triumphalist hagiography need look elsewhere.

In the 13 years since the publication of the draft human genome science has learned a lot about the protein coding regions of our genes – the 1.5 % of our  DNA whose sequence is translated into amino-acids that make up the proteins in our cells – our understanding of the function of the non-coding regions of our genes and the areas in between genes is still in its infancy. This is important because while many inherited diseases are due to errors in the protein coding regions, most of the differences we see between each of us individual human beings and between our species and others are due to differences found in this other 98.5% of our genome.

Dr Arney doesn’t shy away from these gaps in our knowledge and deficiencies in our understanding, she positively revels in them, so if you think we know nearly all there is to know about how are genes work than prepare to be surprised. With the help of her interviewees, she  throws buckets of cold water over some popular (and for some profitable) ideas about how the environment can influence the activity of genes, deftly skewers a few much quoted – but unwise – statements by leading geneticists, and shows how even many standard scientific textbooks are surprisingly inaccurate when it comes to explaining the ways in which genes are organized and regulated within cells.

The  interviewees – who are not all always in agreement with each other – are allowed to tell much of the story, and that’s OK, as it allows the author to show the often messy and imperfect reality of cutting-edge science. She approaches her interviews with a lot of humour and an open mind, but also a determination to get to the heart of the matter. Occasionally the author does allow her impatience with some current trends in genetic research to show, for example when discussing the work of scientists who trawl through the human genome looking for associations between small genetic variations called single nucleotide polymorphisms (a.k.a. SNPs, pronounced snips) and particular traits or diseases (in this case those linked to mental health problems) she writes:

But while this might yield a few more interesting links, I’m increasingly feeling that there are limited further gains to be made… To be fair to the snip-hunters, their discoveries do sometimes provide a useful chisel for researchers to start prising open the biological processes that underpin a disease. Not many people want to do that, though, because it’s hard. It involves doing tricky experiments, often using animal models, and taking years to unpick what’s going on. Much easier to apply for a million-pound grant and go fishing for yet more snips instead (I’ll get off my soap-box for now).

She needn’t apologize; her soap-box moment is most apt. This book is at heart a collection of stories of stories about scientists who spotted something odd in an experiment, and then, rather than shrugging their shoulders and moving on, did the tricky experiments, often using animal models, and put in the years to unpick what’s going on. In most cases they are still unpicking it, but through their failures and successes they have already transformed the way we understand how our genes work.

So who is this book for? It’s perfect for undergraduate biology students who are just starting to learn about genetics,and for those of us who have studied genetics in the past and wish to catch up with the current state of the art, but really it’s for anyone who is curious about how the information in our genes becomes us.

Herding Hemmingway’s Cats is a fascinating, funny, and at times provocative celebration of basic science, and an excellent debut by a new author whose enthusiasm for her subject we are sure will entertain and inform readers around the world.

Paul Browne

Herding Hemmingway’s Cats: Understanding how our genes work by Dr Kat Arney is published by bloomsbury Sigma, and is available in book stores nationwide, and online on Amazon as an audio book, hardback and e-book.

Exciting cells and controlling heartbeats – could optogenetics create drug-free treatments?

A laser-controlled brain or a heart that beats in time to a disco light display sound like some of the more vivid imaginings of science fiction writers. But scientists are gathering together tricks that may allow us to do just that – and they could be used to create drug-free therapies.

This is the growing field of optogenetics, where proteins that change their shapes in response to light pulses can be used to control the electrical activity of cells inside living animals.

The tools have been gathered from far and wide. There are the Channelrhodopsins – sensory receptors – from algae, which respond to blue light, exciting cells by letting positive charges into the cell. The Halorhodopsins, isolated from extremophile bacteria – bacteria living in extreme conditions, in this case salt pools – let negative charge into cells in response to yellow light, and shut the excited cell down. A similar trick to de-excite cells is used by Archeorhodopsins, isolated from another extremophile, which pumps positive charge out of the cell in response to yellow light.

By taking parts from human neurotransmitter receptors and these bacterial light-sensitive domains, we can also create more complicated machines in the lab, such as Hylighter, which depresses activity in neurons on exposure to one colour until it is switched off by exposure to a second colour of light.

Using blue and yellow to manipulate. Lights by Shutterstock

Using blue and yellow to manipulate. Lights by Shutterstock

In theory, this means that by combining pulses of blue and yellow light, neurons and muscles can be switched on and off to order, over incredibly short timescales (thousandths of seconds). Ultimately, this could lead to therapies whereby excitable cells can be “helped along” without the use of drugs and all the dangers that come with long-term use of drug-based cures.

Dancing flies and light-guided fish

Scientists have started exploiting this technology to increase our understanding of the circuits that underpin behaviour, with sometimes spectacular results: flies that dance on cue, for example, or fish that can be steered by light as they swim.

Two studies recently brought the possibilities of light-based electrical stimulation as human therapy to the fore. Researchers at the University of Bonn looked to see if they could control heart beats by applying light simulation to animals whose heart cells were made to express Channelrhodopsin. A combination of Channelrhodopsin and Halorhodopsin allowed another team of researchers to “take over” the heart’s pacemaker cells in zebrafish, overriding its natural rhythm, until the lights were turned off.

Where was I? Mouse by Shutterstock

Where was I? Mouse by Shutterstock

 

In Nobel Prize winner Susumu Tonegawa’s lab, they found that memories that could not be recalled in mice with Alzheimer’s could be retrieved by exposing cells in the brain’s memory forming centres to optogenetic stimulation. Cells that expressed Channelrhodopsin were made more excitable by exposing them to bursts of light, allowing a “power boost” that helped these neurons maintain active connections, in turn helping to retrieve memory of a past event.

This startling result suggested that Alzheimer’s patients could be forming new memories all the time, and may only need a helping hand to maintain the weak connections they form. While this would not stop the changes that make Alzheimer’s patients forget, it might extend the time during which they could retain their memories.

Down to the practicalities

Tonegawa’s study looked at how mice retrieved memories of a sound they had heard at the same time as receiving a short electric shock – something that mice with Alzheimer’s don’t normally remember. After boosting neurons in the brain region that builds these memories by stimulating their firing with Channelrhodpsin, the neurons in this region were helped to form the proper connections to maintain this memory. Tonegawa’s work, then, concentrated on systems that scientists know very well – the fight-or-flight reflexes we develop when something unpleasant happens.

We don’t yet understand the detailed circuitry of the brain that is probably of more interest to Alzheimer’s sufferers and their families: the mechanisms that control the subtle tasks our brain performs for us every day, our recall of loved one’s faces or the location of our car keys. Optogenetics will only ever be as useful as our knowledge of where these fleeting memories are stored.

Nor are these interventions the stuff of emergency medicine. To help an injured heart or a forgetting brain, for example, we would need to know if the patient’s cells were healthy enough to still function, or whether they were too damaged to be properly integrated within their network, which would make exciting them useless.

In this case, we can consider, as some labs have done, taking cells (such as the patient’s own stem cells) and turning them into heart muscle cells or neurons in the lab. If these “replacement” cells can then be made to express Channelrhodposin, for example, they could be injected into damaged tissue in the patient to supply the (light-controlled) function of the original damaged tissue.

This, however, brings up all the associated difficulties that tissue replacement therapies, such as stem cell therapies, create: how to integrate cells into existing tissues, how to stop them integrating where they are not needed, and in the brain, how to get them to integrate into the right networks.

For if excitable cells are found to still be healthy enough to support electrical communication, and to only require optogenetics to turn up the volume of their signals, we still have to get our genetically-encoded construct into the right cells. We also need to find a way to shine light on them (perhaps we would have to wear a fibre-optic pacemaker) and fine tune our stimulation to each individual patient.

For chronic diseases, this may all be worthwhile, but the investment of time and expertise for the procedure will be considerable and is unlikely to change much as the technology advances. It’s clear we have a long way to go, but we may yet have our brains tripping the light fantastic.

Laura Swan, Cell biologist, University of Liverpool

This article was originally published on The Conversation. Read the original article.