Category Archives: Science News

Preventing neuronal death: the future of stroke therapy

In neurological research the importance of neuronal death is well known, as are its implications for the normal functions of your brain. Many serious neurological conditions, such as stroke, epilepsy, traumatic brain injuries, and degenerative diseases like Parkinson’s and Huntington’s Chorea, are a direct consequence of this type of neuronal death, which determines the clinical manifestation of the illness and, as a consequence, the prognosis for the patient.

For example, in stroke an ischemic attack (loss of blood flow), even if it is localized, can initiate the neuronal death program, due to excessive stimulation of neurons (nerve cells) by molecules known as neutotransmitters, the so-called excitotoxic triggers. This in turn leads to a worse clinical development and physical symptoms like palsies, sensory alterations, cognitive impairments and more.

One of the principal triggers of this event is the activation of the N-methyl-D-aspartate receptors on neurons, which are sensitive to glutamic acid, one of the most important excitatory neurotransmitter of the brain.

When these receptors are over activated due to the release of an enormous amount of glutamic acid as a consequence of the lack of oxygen in the affected area of the brain, this triggers a flow of Ca++ ions into the neuron, which activates many enzymes inside the nerve cell that directly damage the internal structure and ultimately cause the cells to die in a process known as apoptosis. (1)

It’s clear at this point how important it is to stop this process in order to prevent progressive damage in areas that are not directly affected by the original ischemic event.

What’s still not so clear is the precise molecular pathway from the liberation of glutamic acid to the neuronal death, but experimental evidence suggests that a membrane protein called JNK (c-Jun-N-terminal-kinase) has an important role in this activation. (2)

Although it has been shown that by blocking JNK it’s possible to reduce infarct size (the size of the damaged area of brain tissue) and neuronal death in an in vivo animal model of cerebral ischemia, the same studies have also shown serious side effects, as JNK has several important physiological functions in the body. As a result researchers have sought to identify means of blocking the role of JNK in ischemia–induced neuronal cell death without blocking its other functions.

It has been demonstrated that JNK is activated by two upstream molecules, called respectively MKK4 and MKK7, that respond to specific stress situations and represent a key bottleneck, and that in particular MKK7 shows an important role as mediator in the activation of JNK as ain response to cerebral ischemia.

Due to this observation, a team of neuroscience Italian researchers developed a specific MKK7 inhibitor peptide, called GADD45ß-I, to study its possible effects in vitro and in vivo in rodent models.(3)

This molecule showed an interesting neuroprotective effect in vitro and no toxicity itself on neurons, suggesting its application for in vivo treatments; during the in vivo (animal research) phase, the molecule was tested on two different rodent models which demonstrated that this peptide could reduce the infarct area of 43% after 24h, if administrated before the induced stroke. Very importantly this neuroprotective effect was still maintained when GADD45ß-I was administered 6h after the initial ischemic damage, which is critical as analysis of earlier failed candidate stroke therapies have stressed that potential therapies must be able to prevent damage when administered several hours after stroke onset (when treating stroke prompt diagnosis and treatment is vital). These protective effects are maintained for at least a week and show that the molecule does not merely delay apoptosis but actively blocks the process.

To prevent ischemic damage in the immediate aftermath of stroke onset, we can use rt-PA (recombinant tissue plasminogen activator) to promote the breakdown of a possible obstruction inside a cerebral artery and prevent a progressive stroke; and this is an important approach that has saved many lives in the last 20 years.  However, this therapy has side effects such as bleeding, and it can be not use in some specific but common conditions, for example in patients who use anticoagulant as Warfarin for atrial fibrillation, and is only effective if administered within 3,5-4,5 hours of stroke onset (although it may be effective later in some cases where the damaged area is clearly demarcated in brain imaging by MRI or CT scan).

All other therapies that are available to neurologists are only supporting therapy for the blood pressure, active anticoagulation and respiratory support where it is necessary.

GADD45ß-I offers the possibility that we could protect a patient under ischemic insult even when we could not use the thrombolytic therapy with rt-PA, and we could also protect them from future insults by regular administration of this drug, which may be especially useful for multimorbidity patient, those who suffer from two or more chronic health conditions.

This could also lead to reduce post-stroke consequences, to improve the prognosis for these persons and to a reduced need for rehabilitative therapies as physiotherapy, speech therapy and exercise therapy

If these promising early results are confirmed in clinical trials, this therapy could be one of the most important discoveries in the field of neurology in the recent years and could radically change our approach on stroke, allowing us to switch from a supportive therapy to a preventative therapy.

If we think that in 2010 circa 17 million stroke occurred worldwide, and that every 6 seconds a person somewhere suffers a stroke, we can also imagine the potential impact of this therapy.

  1. Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov 2006; 5: 160–170.
  2. Centeno C, Repici M, Chatton JY, Riederer BM, Bonny C, Nicod P et al. Role of the JNK pathway in NMDA-mediated excitotoxicity of cortical neurons. Cell Death Differ 2007; 14: 240–253.
  3. Vercelli A, Biggi S, Sclip A, Repetto IE, Cimini S, Falleroni F, Tomasi S, Monti R, Tonna N, Morelli F, Grande V, Stravalaci M, Biasini E, Marin O, Bianco F, di Marino D, Borsello T. Exploring the role of MKK7 in excitotoxicity and cerebral ischemia: a novel pharmacological strategy against brain injury. Cell Death Dis. 2015 Aug 13;6: e1854.



UK Government Minister says animal research is ‘vital tool’ for developing new treatments

Patrick Grady, the shadow Scottish National Party spokesman on International Development, recently asked the Government in parliamentary question, on 26th October 2015, if they would “issue a response to EDM 373, Applying Results of Experiments on Animals to Humans.”

Early Day Motion’s (EDMs) are regularly used by lobbyists to push their agenda, however their actual impact is minimal. EDM373 is the product of campaigning group, For Life on Earth which runs under a multitude of names including Patients Campaigning for Cures, NO to Animal Experiments, Oppose B&K Universal, Speaking of human based research and more. The group is inspired by the writing of Dr Ray Greek, and his Trans-Species Modeling Theory (a theory that few have heard of and even fewer subscribe to).

The EDM is the third time the motion has been made in three years (in 2014/15 it was EDM22, in 2013/14 it was EDM263) – with essentially the same message:

That this House notes the science-based campaign, For Life On Earth, which is critical of avoidable experiments on animals; further notes the new initiative, Patients Campaigning For Cures, which opposes animal models on medical grounds; is alarmed that scientific studies reveal that the widespread claimed ability of animals to predict human responses to drugs and disease is demonstrably false; acknowledges that over 90 per cent of drugs which test well in animals harm or otherwise fail humans, and that ignoring this has delayed cures including penicillin; notes that using animals to model humans contradicts currently accepted science, including evolutionary biology and genetics, which supports personalised medical care; further acknowledges the proclamation of the Concordat on Openness on Animal Research to develop communications with the media and public; and calls for thorough, properly moderated public scientific debate on the misleading and costly practice of trying to apply results from animal experiments to human patients.

So we have the usual myths about 90% failure rates, penicillin, and delays in other treatments. There is also typical Ray Greek-inspired fluff about “currently accepted science”. Their demands for a debate might be reasonable (though debating and science are very different kettles of fish), though the conditions being set on the terms for this debate are not (see the last response from Understanding Animal Research on this subject).

Thankfully, the UK Government wasn’t falling for it. Jo Johnson MP, British Minister of State for Universities and Science, gave a strong response to the parliamentary question.

The Government considers that the carefully regulated use of animals in scientific research remains a vital tool in improving the understanding of how biological systems work and in the development of safe new medicines, treatments and technologies.

At the same time, the Government believes that animals should only be used when there is no practicable alternative and it actively supports and funds the development and dissemination of techniques that replace, reduce and refine the use of animals in research (the 3Rs), in particular through funding for the National Centre for the 3Rs, and also through ongoing UK-led efforts to encourage greater global uptake of the 3Rs.

Advances in biomedical science and technologies – including stem cell research, in vitro systems that mimic the function of human organs, imaging and new computer modelling techniques – are all providing new opportunities to reduce reliance on the use of animals in research. As part of this, Innovate UK is awarding £4m this year to fund collaborative projects with industry to support the development and application of new non-animal technologies.

EU and UK law requires safety testing on animals before human trials for new medicines can begin and animal research still plays an important role in providing vital safety information for potential new medicines.

The Early Day Motion (EDM 373) rightly draws attention to the UK life science sector’s Concordat on openness in animal research which was launched last year, and provides new opportunities for transparency and debate in this area.

Jo Johnson MP tours Cardiff University

Jo Johnson MP tours Cardiff University

Importance of animal research, use and development of alternatives and strict regulations are all mentioned in the response.

This question comes days after the UK Government released the annual statistics on animal research showing a slight dip in the number of procedures carried out.

Speaking of Research

One step closer to a vaccine for cytomegalovirus: Monkeys transmit CMV the same way as humans

Today’s guest post is by Jordana Lenon, Wisconsin National Primate Research Center and Kathy West, California National Primate Research Center.

PregnantWomanResearchers at Duke and Tulane take the lead, the National Primate Research Centers provide critical resources and expertise in this first-ever proof of CMV placental transmission in nonhuman primates.

Researchers now have a powerful new model for working on a vaccine for cytomegalovirus, or CMV, which is the leading infectious cause of birth defects worldwide.

Now, for the first time, a nonhuman primate CMV has been demonstrated to be congenitally transmitted similar to congenital HCMV infection. The discovery was published this week in the high impact journal Proceedings of the National Academy of Sciences and reported in The New York Times and Science Daily, among other news outlets.

Rhesus macaque mothers can transmit CMV across their placentas to their unborn infants, discovered the teams of co-senior study authors Sallie R. Permar, M.D., Ph.D., Duke University, and Amitinder Kaur, M.D., Tulane University. The lead author was Kristy Bialas, a post-doctoral fellow at the Duke Human Vaccine Institute.

Rhesus monkeys at the California National Primate Research Center. Photo credit: Kathy West

Rhesus monkeys at the California National Primate Research Center. Photo credit: Kathy West

The finding establishes the first nonhuman primate research model for CMV transmission via the placenta. The macaque reproductive, developmental, and immunological systems are highly analogous to those of humans. Thus, scientists can now utilize the biologically relevant RhCMV system in a controlled scientific setting to try to find new pathways towards an HCMV vaccine.

“A huge impediment to CMV vaccine development has been our lack of ability to determine what immune responses would be needed to protect against mother-to-fetus transmission,” said Permar, of the Duke Human Vaccine Institute in a Duke Medicine news release Oct. 19.

“It means that we can now use this model to ask questions about protective immunity against congenital CMV and actually study this disease for which a vaccine is urgently needed,” said co-senior author Kaur, of the Tulane National Primate Research Center in a Tulane University release Oct. 19.

The rhesus monkey model for HCMV persistence and pathogenesis has been developed over the past 30 years by co-author Peter Barry, Ph.D., California National Primate Research Center (CNPRC) core scientist, and co-developer of the rhesus intrauterine pathogenesis model with Alice Tarantal, Ph.D., CNPRC core scientist. Barry has recently shown that there is a strong immune response in rhesus monkeys to a potentially paradigm-shifting approach to HCMV vaccine design, and contributed important expertise and resources to this current research.

CNPRCrhesus,K_WestUCD, 4

Rhesus monkeys at the California National Primate Research Center. Photo credit: Kathy West

The work highlights the collaboration of Duke University researchers with experts in rhesus immunology and virology at the National Institutes of Health National Primate Research Centers. Contributing authors also included David O’Connor, Ph.D., and Michael Lauck, Ph.D., experts in macaque virology, pathology and genetics at the Wisconsin National Primate Research Center, Xavier Alvarez, Ph.D., at the Tulane National Primate Research Center, and Takayuki Tanaka, D.V.M., Harvard Medical School and the New England National Primate Research Center, which provided macaques for the study. Additional authors’ contributions are included in the Duke news release.

The research was funded by National Institutes of Health (NIH) Office of the Director, NIH National Cancer Institute, NIH National Institute of Allergy and Infectious Diseases, NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Derfner Children’s Miracle Network Research Grant.


Kristy M. Bialas et al. “Maternal CD4+ T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission” Proc Natl Acad Sci U S A. 2015 Oct 19.

Animal Experiments in the UK: Government releases 2014 statistics

The UK Home Office has published its annual statistics showing the number of procedures carried out on animals covered by the Animals (Scientific Procedures) Act, 1986; this covers all vertebrate species. It shows that in 2014 there was a 6% fall in the number of procedures, from 4.12 million down to 3.87 million.

Click to Enlarge

Overall, 96.5% of animals used in scientific studies were mice, rats, fish or birds. Cats, dogs and primates (which are offered special protections under UK law) together accounted for less than 0.2% of the total (similar to in previous years). The statistics also reveal that half of all experiments were the breeding of GM animals which were not used in further experiments. Overall, 2/3 of all experiments involved genetically modified animals.

Number of Animals Used For Research in the UK 1945 - 2014

Last year’s plateau, and this year’s fall are likely to reflect the economic conditions for biomedical research (though the number of procedures is likely to lag R&D spending as research funding can last several years. Below we see the R&D expenditure of pharmaceutical companies in the UK over the last decade (note that this does not include R&D by universities, who conduct almost twice as much animal research in the UK as pharmaceutical companies). Spending slowed in 2012, which may be reflected in the animal numbers for 2014.

Pharmaceutical R&D in the UK

The fall in numbers may also be in influenced by further adoption of the 3Rs – Replacement, Refinement and Reduction. Home Office Minister, Lord Bates noted:

Today’s figures indicate the science community continues to respond to the Government’s firm commitment to adopting measures to replace, reduce and refine animal use.

Procedures on non-human primates stayed almost constant going from 3,236 procedures in 2013, to 3,246 in 2014. The number of procedures on cats fell 22% to 210 procedures and on dogs fell 14% to 4,107.

A ban on cosmetic testing on animals (1998) and of using great apes (gorillas, orang-utans and chimpanzees) in research (1986) meant both had zero procedures in 2014. There were 138 household product tests, all on rainbow trout for EU regulatory purposes. This comes after 2 years where no such tests have been done – household product testing on animals will be banned in November 2015.

For the first time the UK statistics include retrospective reporting of suffering. Rather than just submitting licence proposals to the Home Office that include estimated levels of suffering, the researchers now have to report on what was actually seen (using a variety of measures). Unfortunately the statistics put these in two separate tables (Table 3 and 8). So we have combined them to get severity for all procedures in 2014. We can see most experiments are sub threshold (28%; less than the introduction of a hypodermic needle) or mild (50%), with remainder as moderate (14%), severe (5%) or non-recovery (3.5%; the animal never awakes from anaesthesia).

Severity of procedures 2014 UK

It is important to note that in line with new EU requirements, the UK now reports animals used in studies completed, not started in the given year. The statistical release says:

As a result of the change to counting procedures completed as opposed to procedures started, all procedures started before 2014 but completed in 2014 should be in both the pre-2014 and 2014 figures. Any procedures started in 2014 but completed after 2014 will not be included in the 2014 figures. It is expected that these opposing effects will partly cancel each other out. Any impact of the change from counting procedures started to counting procedures completed will be temporary and will disappear from future years’ data collections.

Finally noting:

As a result, the 2014 data and comparisons with previous years’ data should be interpreted with some caution.

Speaking of Research congratulate the UK government on continuing to produce the most comprehensive statistics on animal experiments worldwide. It is also important to note that these statistics are released as a press conference each year where representatives from the scientific community speak about the importance of animals in research.

Speaking of Research

Find more on the stats here:

Read last year’s release here:

NABR letter: “Is the American Association for the Advancement of Science Anti-Science?”

The letter below, from Frankie Trull of the National Association for Biomedical Research,  is reprinted with permission from NABR. It was sent on October 8, 2015 to Dr. Rush Holt, Chief Executive Officer of the American Association for the Advancement of Science; Dr. Marcia K. McNutt, Editor-in-Chief, Science family of journals, AAAS; and Mr. Tim Appenzeller, News Editor, Science, AAAS.

nabr index

National Association for Biomedical Research






Dear Drs. Holt, McNutt and Mr. Appenzeller:

We are writing to express our concerns with the recent coverage in Science Insider featuring the Beagle Freedom Project, an animal activist organization. The fact that a publication of the American Association for the Advancement of Science has seemingly become a mouthpiece for an organization counting among its officers a felon convicted under the federal Animal Enterprise Terrorism Act is very troubling. Further it is difficult to imagine how continuously featuring the efforts of animal rights groups dedicated to ending animal research advances science, which is embodied in the very name, AAAS.

The most recent example of such anti-science reporting has been written by a member of the Science staff who appears to have his own agenda. The article in question highlights the efforts of a group dedicated to eliminating canines as a proven and valued animal model, and it is worth noting this author also published a book that appears to advocate human legal protections for canines. The article demonstrates a clear bias.

The same author also recently devoted multiple pages in Science to a lengthy profile of an animal rights activist working for PETA. NABR expressed its dismay with this unprecedented coverage in the pages of Science in a letter to Dr. McNutt and to your predecessor, Dr. Alan Leshner on January 26, 2015. AAAS and its related science publications have provided extensive coverage which either directly or by implication negatively portray animals as research models. A partial listing of stories is included below:

  • September 17, 2015 – Nature changes animal policy after cancer study comes under fire
  • August 21, 2015 – Crowdsourcing animal research
  • August 18, 2015 – Has U.S. biomedical research on chimpanzees come to an end?
  • August 12, 2015 – Animal advocacy group targets cat and dog research using novel crowdsourcing campaign
  • July 30, 2015 – Judge rules research chimps are not ‘legal persons’
  • July 10, 2015 – Use of regulated animals in U.S. biomedical research falls to lowest levels on record
  • June 12, 2015 – The scientist behind the ‘personhood’ chimps
  • June 12, 2015 – Research chimps to be listed as ‘endangered’
  • April 20, 2015 – Judge’s ruling grants legal right to research chimps
  • April 16, 2015 – How dogs stole our hearts
  • April 13, 2015 – Monkey deaths prompt probe of Harvard primate facility
  • January 23, 2015 – The insurgent (lengthy profile of PETA activist Justin Goodman)
  • January 22, 2015 – Slideshow: PETA’s crusade against animal research
  • August 29, 2014 – Animal welfare accreditation called into question
  • December 6, 2013 – Lawsuits Seek ‘Personhood’ for Chimpanzees
  • February 26, 2010 – Dog Dealers’ Days May Be Numbered

In reference to the August 29, 2014 article “Animal welfare accreditation called into question,” Science chose to highlight a study in which the authors are not only affiliated with a well-known animal activist group, but who also refuse to share the data supporting their study making it unreproducible. In essence, Science ran a story about a study whose authors have adopted a position that AAAS, most other scientific publishers, and funding agencies reject; a policy that could easily invite fraud, dishonesty and questionable science. It is incomprehensible that Science would then choose to honor one of these activist authors with a lengthy and biased profile.

To the best of our knowledge, AAAS publications are not in the practice of publishing articles that provide a platform to other special interests with political agendas such as anti-climate change, pro-tobacco, anti-GMO or anti-human embryonic stem cells. This leaves us to question why Science has devoted so much time and space specifically to individuals and organizations opposed to essential basic and biomedical animal research.

There has been significant coverage in The Atlantic, PBS NewsHour, and most recently the New York Times highlighting the role of the chimpanzee model in vaccine research which aims to protect wild chimpanzee populations from devastating Ebola outbreaks. These articles rightly question whether policy makers have acted too hastily in making research with chimpanzees in the U.S. more difficult, and in some cases, impossible. Yet AAAS publications seem to have spoken with their silence by providing no coverage on this contentious debate. Many biomedical researchers are now questioning whether AAAS publications have abandoned their biomedical research constituents in favor of groups with animal rights agendas.

We strongly urge AAAS to support biomedical research and the scientific community, and to maintain the high standard of reporting excellence that has defined Science and ScienceInsider. Your own constituents in the research community and the many members of the public respect AAAS’ commitment to scientific rigor and factual evidence. We are hopeful that your recent detour into animal rights hyperbole, personal opinion, and special interests is an aberration that will be corrected. In the meantime we will keep our members well-informed with regard to these concerns.


Frankie L. Trull, President, NABR


Caveat Emptor

A current USDA case involving a major antibody producer underscores the need for the research community to demonstrate its commitment to high standards of animal welfare.

On August 18-20, 2015, Santa Cruz Biotechnology, Inc. (SCBT) went before Administrative Law Judge Janice Bullard in Washington to rebut charges of Animal Welfare Act (AWA) violations at its California antibody production site. The hearing was supposed to conclude on August 21. However, according to an account of the hearing posted by the Animal Welfare Institute (“Key Hearing in DC from August 18 to August 20”), the proceedings were suspended on the last day and the parties were given until September 30, 2015 to negotiate a settlement. As of this writing, no settlement agreement has been reached. Therefore the allegations against SCBT remain just that—allegations: Final judgment must be withheld until the legal proceedings are concluded. Nevertheless, the seriousness of the USDA’s charges against SCBT demands attention.

Why antibodies matter

Antibodies play an increasingly important role in both clinical medicine and research. The immune system generates antibodies when it detects a foreign protein. Antibodies are proteins that tag these “invaders,” enabling other immune cells to find and destroy them. Because each antibody targets a single protein, they also have many useful applications. Antibodies can be used to diagnose and treat diseases, such as cancer and autoimmune conditions including rheumatoid arthritis and inflammatory bowel disease. Just this past August the U.S. Food and Drug Administration approved the antibody-based drug Repatha (evolocumab), the second in a new class of drugs that can lower cholesterol dramatically by targeting a specific protein.

Antibodies are also widely used in research to detect specific proteins in blood or tissue:

Yates lab neurotransmitter photo

Antibodies “light up” a neurotransmitter in this sample of brain tissue. Yates laboratory, University of Pittsburgh

Antibody production is a multi-billion dollar industry, and SCBT is a major player.

Making antibodies

Antibody production starts by injecting animals with the protein to be tagged. One production method involves collecting blood from animals injected with the protein and then extracting the antibodies. This method produces polyclonal antibodies that are comprised of a collection of immune cells.

Another method uses hybridoma technology which produces monoclonal antibodies that consist of only one type of immune cell. This method also begins by injecting an animal with the protein to be tagged. The next step is to remove an initial batch of antibody- producing cells from the animal’s blood and fuse them with a harmless cancer cell to produce a cell line that can generate the desired antibody in the lab. César Milstein and Georges J. F. Köhler shared the 1975 Nobel Prize in Physiology or Medicine for developing this methodology.

When performed properly, the creation of antibodies using either of these methods causes minimal pain or distress to animals.

SCBT produces antibodies with various animals including goats and rabbits, species regulated under the AWA. The USDA sends inspectors at least once a year to visit all facilities that conduct research, teaching, or testing with regulated animal species to ensure their compliance with the AWA.

In a formal complaint filed August 7, 2015, the USDA accused SCBT of “repeated failures to provide minimally-adequate and expeditious veterinary care and treatment to animals” (2015 complaint, paragraph 5). USDA said further that the company had “demonstrated bad faith by misleading APHIS personnel about the existence of an undisclosed location” where goats were housed (2015 complaint, paragraph 6).

SCBT history of non-compliance citations

This was not the first time SCBT has been cited for AWA compliance issues. According to the August 7, 2015 complaint, in July, 2005, the company paid a $4,600 penalty to resolve allegations of AWA violations from 2002-2004 (2015 complaint, paragraph 7). Seven years later, on July 19, 2012, USDA filed a complaint against SCBT alleging the following:

  • SCBT failed to “establish and maintain programs of adequate veterinary care.” (2012 complaint, paragraphs III. B.-C based on findings from a July 13, 2010 inspection; 2012 complaint, paragraphs IV. C.-D, based on findings from a February 8, 2011 inspection; and 2012 complaint, paragraph VI. B. 5, based on findings from a March 6, 2012 inspection);
  • During the March 6, 2012 inspection, the inspector cited SCBT for not only having “failed to establish and maintain programs of adequate veterinary care under the supervision and assistance of a doctor of veterinary medicine,” but also having “failed to provide veterinary care to animals in need of care.” (2012 complaint, paragraph VI. A);
  • On July 13, 2010, the USDA inspector cited SCBT for animal care staff who were not properly trained. (2012 complaint, paragraphs III. A.-B. and E.1);
  • On July 24, 2007, the USDA inspector cited SCBT for improper handling of animals. (2012 complaint, paragraph II.D.1.-2).

The 2012 complaint also noted various shortcomings of SCBT’s institutional animal care and use committee or “IACUC.” According to the AWA, the IACUC is required to “assess the research facility’s animal program, facilities, and procedures,” including semi-annual inspections of the facilities that identify and report “significant deficiencies.” (9 C.F.R. section 2.31 (c) (1-3)) A significant deficiency is defined in 9 C.F.R. section 2.31 (c) (3) as a problem that “is or may be a threat to the health or safety of the animals.” The IACUC is also required to review and approve animal use protocols before the research commences, to review and approve significant changes to ongoing protocols, and to ensure that animal pain and distress are minimized.

The 2012 complaint alleged these problems with SCBT’s IACUC:

  • The AWA requires the IACUC to determine that the principal investigator had considered alternatives to potentially painful procedures and failure to ensure that the animals’ pain and distress would be minimized by providing pain relieving drugs unless there was scientific justification to withhold them. (9 C.F.R. 2.31 (d) (1) (ii)) Alleged failures of the SCBT IACUC to do so were noted in the July 24, 2007 inspection (2012 complaint, paragraphs II. B.-C); the February 8, 2011 inspection (2012 complaint, paragraphs IV.A.-B); and the March 6, 2012 inspection (2012 complaint, paragraph VI. B. 2);
  • The AWA requires the IACUC to review and approve significant changes to an ongoing activity. (9 C.F.R. 2.31 (c) (7)) On March 6, 2012, the USDA inspector cited SCBT for an alleged failure of its IACUC to review significant changes. (2012 complaint, paragraph VI.B.1);
  • The AWA requires the IACUC to determine that animals are housed in conditions appropriate for their species. (9 C.F.R. 2.31 (d) (1)) On March 6, 2012, the USDA inspector cited SCBT for an alleged failure of its IACUC to ensure appropriate housing for animals at the facility. (2012 complaint, paragraph VI. B. 3)
Photo credit: Dan Coyro -- Santa Cruz Sentinel

Photo credit: Dan Coyro — Santa Cruz Sentinel

2014 hearing delayed

The 2012 complaint was to have been adjudicated in 2014, but the hearing was called off two weeks before it was scheduled to take place. According to a July 1, 2014 notice issued by Administrative Law Judge Jill S. Clifton, the hearing was cancelled to give SCBT and USDA “ample time to meet to further their attempts to settle the case.” However, no resolution to the allegations in the complaint was announced, and during subsequent visits, USDA inspectors identified more alleged AWA violations at SCBT.

On November 4, 2014, USDA filed a second formal complaint listing alleged violations found during 7 inspections between September 26, 2012 and April 22, 2014. The second complaint charged SCBT with having “failed to allow APHIS officials to inspect” a barn known as Lake Ranch/H7 “from at least March 6, 2012, through October 30, 2012.” (2014 complaint, paragraph III). This complaint also listed additional instances of failures to provide adequate veterinary care based upon findings from inspections of October 31, 2012 (2014 complaint, paragraph IV. B), December 18, 2012 inspection (paragraph V); and February 20, 2013 (paragraph VI).

The 2014 complaint also included these allegations:

  • The AWA requires the IACUC to ensure that the proposed activities or significant changes in ongoing activities “will avoid or minimize discomfort, distress, and pain to the animals.” (9 C.F.R. 2.31 (d) (i)) On September 26, 2012, the USDA alleged that SCBT’s had failed to execute this requirement. (2014 complaint, paragraph II. A);
  • The AWA requires the IACUC to “review and approve, require modifications in (to secure approval) or withhold approval of proposed significant changes regarding the care and use of animals in ongoing activities.” (9 C.F.R. 2.31 (c) (7)) Alleged failures of the SCBT IACUC to do so were noted during the inspections of October 31, 2012 (2014 complaint, paragraph IV.A); May 14, 2013 (paragraph VII); and April 22, 2014 (paragraph IX.A.-B);

The 2014 complaint further listed problems with the housing, food, and water provided to animals. These problems were noted in the September 26, 2012 inspection (cited in paragraph II. C. 1-4 of the 2014 complaint as alleged violations of 9 C.F.R. Sections 3.125 (a), 3.129 (a), 3.131 (a) and (d)); in the October 31, 2012 inspection (cited in paragraph IV.C. as alleged violations of 9 C.F.R. Sections 2.26, 2.100 (a), and 3.131 (c)); in the September 10, 2013 inspection (cited in paragraph VIII.1 as alleged violations of 9 C.F.R. Section 3.127 (a)); and in the April 22, 2014 inspection (cited in paragraph IX. C.1-3 as alleged violations of 9 C.F.R. Sections 3.56 (a), 3.54 (a), and 3.129 (a)).

USDA’s latest complaint

The third USDA complaint was filed August 7, 2015 and reported by the Santa Cruz Sentinel under the headline: “Santa Cruz Biotech faces third USDA complaint alleging animal mistreatment.” As noted above, this complaint asserted that the company had “demonstrated bad faith by misleading APHIS personnel about the existence of an undisclosed location where respondent housed regulated animals.” (2015 complaint, paragraph 6) It also alleged that SCBT had “repeated[ly] failure[d] to provide minimally-adequate and expeditious veterinary care and treatment to animals.” (paragraph 5) In support of this allegation, subparagraphs 8. a.-n. of the complaint describe 14 instances between 2011 and 2015 where USDA inspectors observed individual goats that appeared to be in poor health and lacking appropriate veterinary care. Several of these goats were thin, appeared anemic or seemed to be suffering from infections (subparagraphs 8 a., b., c., d., g., j., k., l., and m.), while others had wounds or other injuries (subparagraphs 8.e., f., and i.).

These were two of the most serious cases:

  • “Respondent failed to provide adequate veterinary care to a goat (#12267) that sustained a rattlesnake bite on April 28, 2012, and following initial treatment, the goat’s condition did not improve, and the goat was not given any further treatment until its death. Specifically, the goat developed a visibly swollen jaw and chest and draining lesion and experienced a 23% weight loss (24 pounds) between April 28 and May 9, 2012. By APHIS’s inspection on May 24, 2012, the goat was observed to be unable or unwilling to close its mouth, which, in conjunction with the goat’s other visible conditions, indicated that the goat was unable to eat normally. On June 10, 2012, the goat was observed to have labored breathing, but was not euthanized June 11, 2012.” (2015 complaint, sub paragraph 8.f.);
  • “Respondent failed to provide adequate veterinary care to a goat (#21135) that had been diagnosed with urinary calculi [kidney stones] and treated with ace promazine. On July 7, 2015, at approximately 10:30 a.m., APHIS inspectors found the goat in a depressed posture, unwilling to walk, and breathing heavily. Respondent had no veterinarian available to attend to this animal: the respondent’s ‘on-site’ veterinarian was on vacation, and respondent’s staff could not contact respondent’s attending veterinarian, or any other veterinarian who could provide emergency care. By 3:30 p.m., the goat was agonal [gasping for breath], suffering and in distress. Respondent failed to follow its own ‘Standard Operating Procedure’ for emergency goat euthanasia, which requires veterinary approval for euthanasia. As no veterinarian was available, respondent’s staff used a captive bolt gun alone (without a sedative or secondary euthanasia injection,) to effect euthanasia of the goat at approximately 4:15 p.m.” (2015 complaint, subparagraph 8.n.).

As of this writing, there has been no judicial resolution of the alleged AWA violations by SCBT. That is to say, neither a settlement between USDA and SCBT nor a continuation of the administrative hearing has been announced.

Animal welfare matters

On February 14, 2014, Cat Ferguson wrote in The New Yorker about alleged animal welfare problems at SCBT, “Valuable Antibodies at a High Cost”. On September 25, 2015, science writer Meredith Wadman published an opinion article in the San Jose Mercury News about the 4-day hearing the previous month. In “No excuse for cruelty to goats raised for medical research,” Wadman opined that researchers were “the only constituency that Santa Cruz cares about,” and urged them to “weigh in” using their purchasing power. According to Wadman, Matt Scott of the Carnegie Institution for Science and Pamela Björkman of the California Institute of Technology have stopped buying antibodies from SCBT. Wadman concluded by asking, “Is it too much to ask other scientists to follow suit?”

Testimony from USDA Veterinary Medical Officer Marcy Rosendale was reported in an account of the August 18-20, 2015 hearing posted by the Animal Welfare Institute. According to this report, Rosendale said she had not observed the same number of animal welfare problems she found at SCBT at other antibody production facilities she had visited.

There is growing recognition that to ensure the rigor of their work, scientists need more information about the antibodies they use actually, i.e., technical specifications such as the what part of the target protein the antibody binds to. Perhaps it is also time to pay more attention to how those antibodies are produced.

USDA inspections are a matter of public record, but meeting the requirements of the AWA should only be the beginning. Antibody producers should be encouraged to take additional steps to affirm their commitment to animal welfare, such as by seeking independent accreditation of their production facilities through AAALAC. The point is that researchers and antibody producers alike must find tangible ways to demonstrate a commitment to high standards of animal care.

Alice Ra’anan and Bill Yates

Previous posts about SCBT and antibodies:

USDA documents:

USDA – 1st SCBT complaint 19 July 2012

USDA – 2nd SCBT complaint 4 Nov 2014

USDA – 3rd SCBT complaint 7 Aug 2015

Nobel Prize 2015 – Protecting People against Parasites!

The 2015 Nobel Prize in Physiology or Medicine has been awarded to scientists whose research has led to therapies that have saved hundreds of millions of people around the world from parasitic diseases that can otherwise cause disability and death.

William C. Campbell and Satoshi Ōmura shared one half of the award “for their discoveries concerning a novel therapy against infections caused by roundworm parasites”, while Youyou Tu was awarded the other half “for her discoveries concerning a novel therapy against Malaria”.

Portraits of the winners of the Nobel medicine prize, shown on a screen at the ceremony in Stockholm. Photograph: Jonathan Nackstrand/AFP/Getty Images

Portraits of the winners of the Nobel medicine prize, shown on a screen at the ceremony in Stockholm. Photograph: Jonathan Nackstrand/AFP/Getty Images

In the press release announcing the award the Nobel Assembly at the Karolinska Institute highlighted the impact of the therapies that were developed thanks to the work done by these three scientists, Avermectin in the case of William C. Campbell and Satoshi Ōmura, and Artemisinin in the case of Youyou Tu.

The discoveries of Avermectin and Artemisinin have fundamentally changed the treatment of parasitic diseases. Today the Avermectin-derivative Ivermectin is used in all parts of the world that are plagued by parasitic diseases. Ivermectin is highly effective against a range of parasites, has limited side effects and is freely available across the globe. The importance of Ivermectin for improving the health and wellbeing of millions of individuals with River Blindness and Lymphatic Filariasis, primarily in the poorest regions of the world, is immeasurable. Treatment is so successful that these diseases are on the verge of eradication, which would be a major feat in the medical history of humankind. Malaria infects close to 200 million individuals yearly. Artemisinin is used in all Malaria-ridden parts of the world. When used in combination therapy, it is estimated to reduce mortality from Malaria by more than 20% overall and by more than 30% in children.

For Africa alone, this means that more than 100 000 lives are saved each year.

The discoveries of Avermectin and Artemisinin have revolutionized therapy for patients suffering from devastating parasitic diseases. Campbell, Ōmura and Tu have transformed the treatment of parasitic diseases. The global impact of their discoveries and the resulting benefit to mankind are immeasurable.

Animal research played a key part in the development of these therapies, as the Nobel Prize press release has pointed out.



In the case of Avermectin, after  Satoshi Ōmura had identified a series of bacterial cultures that produced a variety of antimicrobial agents, including the bacteria Streptomyces avermitilis which  showed promise against parasitic roundworm infection in mice, in 1979 William C. Campbell and colleagues identified a particular component produced by S. avermitilis called Avermectin B1a which had a broad efficiency against roundworm infections in a wide range of domesticated animal species, including cattle, sheep, dogs and chickens. Following this the team developed a modified form of Avermectin B1a known as Ivermectin, which was entered into clinical trials following positive tests in animal models of parasitic infection, and has since gone on to become a key treatment for parasitic infections – particularly the nematode worm infections that cause River Blindness and  Lymphatic Filariasis (the extreme manifestation of which is known as elephantitis) – and is on the World Health Organization’s list of Essential Medicines.



Ivermectin, and other members of the Avermectin family of therapies, are also widely used in veterinary practice, and their development and use is a good example of the One Health principle in action. You can learn more about the discovery of the Avermectins and Artemisinins in the advanced material Avermectin and Artemisinin – Revolutionary Therapies against Parasitic Diseases produced by the Nobel Assembly.

In 2011 we took a look at Professor Youyou Tu’s research that led to the development of Artemisinin therapy for malaria, and the key role played by mouse models of malaria infection,  in a post entitled “George is OK: Thank the men who stare down microscopes!”

While the news reports don’t state which drugs Cloony took to beat malaria, It is most likely that he was treated with artemisinin-based combination therapies (ACTs), which became available in the late 1990s and are now in widespread use.  If that is the case, he has benefited from mouse studies done in China the late 1960s and early 1970s when over 100 traditional herbal remedies were screened in a rodent model of malaria for anti-malarial activity (1). Eventually “Project 523” scored a hit when Professor Tu Youyou identified an extract of the plant qinghao, scientific name Artemisia annua, which had good anti-malarial activity, leading to the development of the artemisinin-based anti-malarials which have become the first-line treatment for malaria in the past decade.

We congratulate this years Nobel laureates in Physiology or Medicine, their research has improved the lives of hundreds of millions of people across the world over the past 3 decades, and will continue to do so. We hope that their success continues to inspire scientists around the world to rise to current and future public health challenges!

Speaking of Research