Author Archives: allysonjbennett

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.

Guest Post. How to Engage with the Public About Animal Research: Society for Neuroscience Panelists Offer Strategies to Scientists During Annual Meeting

Today’s guest post is from Amanda Dettmer, Ph.D.,  a Postdoctoral Fellow at the Eunice Kennedy Shriver National Institute of Child Health & Human Development. Dr. Dettmer is a developmental psychobiologist whose research examines the early life organization of sociocognitive development in nonhuman primates. She received her PhD in Neuroscience & Behavior from the University of Massachusetts Amherst in 2009. You can follow her on Twitter.
Dr. Amanda Dettmer

Dr. Amanda Dettmer


During their annual meeting in Chicago, the Society for Neuroscience (SFN) yesterday held a 2-hour lunchtime session dedicated to public outreach concerning animals in research. The panelists were international experts on communicating the importance of animal research to the public, and they offered invaluable advice to the hundreds of scientists in attendance.

While it’s clear that scientists – and the institutions that employ them – must be more proactive in communicating the importance of their research and the animal models they use, the panelists offered several tangible pieces of advice on how to achieve this goal. The strategies offered cater to researchers working with various animal models and, more importantly, with varying degrees of comfort in engaging the public in their research.

The session opened with remarks by the chair of the SFN’s Animals in Research Committee, Dr. Michael Goldberg, who stated, “We’ve been staying under the radar to avoid animals rights activists, and this strategy is not working,” particularly with respect to nonhuman primates in research. Earlier this year, Goldberg and the President of SFN, Dr. Steve Hyman, submitted a letter to Science in response to an article published there, “Embattled Max Planck neuroscientist quits primate research.”

AM15_Logo_CMYK_Horizontal_SavedForWebThe first panelist, Dr. Rolf Zeller, is the founding president of the Basel Declaration Society (BDS) and a founding signatory of the Basel Declaration, by which researchers recognize the necessity of animal research in biomedical research, and endorse the highest standards of ethically responsible animal research. Stating that researchers will “never convince PETA, but we can convince the public,” Zeller stressed the importance of engaging the public and offered the BDS’ most effective strategies for communication in Europe: regular media training sessions for trainees and established scientists, persistent use of social media, and open access publications on scientific communication. Zeller offered his “Golden Rules” for public outreach, which included:

  • 1) Receive good training in science communication,
  • 2) Be proactive and honest about your research,
  • 3) Discuss your animal research with colleagues, especially any who might be skeptical, so that they understand why it is important,
  • 4) Make it clear you care about animals,
  • 5) Explain why animal research is essential for patients, and
  • 6) Join the BSD and sign the Declaration to be part of a proactive community.
Pro-Test Italia

Pro-Test Italia

Dario Padovan, President of Pro-TEST Italia, a non-profit that “aims to promote and disseminate to the public correct knowledge on scientific research,” followed with an emboldening presentation on how the group increased positive public perception of animal research in Italy with regular strategies easily and equally employable in the US: 1) active, daily activity on social media (the group responds to every incorrect/negative Facebook comment on their page, 2) engaging young scientific experts to reach their contemporaries (saying “most users of social media are 18-34 years”), 3) regularly producing YouTube videos that show detailed primate research in a humane and responsible way (which receive tens of thousands of views and >90% net “thumbs up” ratings), 4) fighting fire with fire by creating satirical anti-animal rights propaganda, and 5) getting patients who benefit from animal research involved in public outreach.

Pigtail macaques at the Washington National Primate Research Center

Pigtail macaques at the Washington National Primate Research Center

Dr. Michael Mustari, Director of the Washington National Primate Research Center, then highlighted the outstanding care that nonhuman primates at his, and all of the other six, National Primate Research Centers in the US, receive, as well as the significant contributions primates have made in the advances of such diseases as HIV/AIDS, polio, ebola, and Parkinson’s disease.

Mustari said, “People who argue against nonhuman primate work do not pay attention to reality.” He drove home the need to engage with the public by showing the type of video that the public needs to see regularly to understand the value of primates in research, like this one showing a quadriplegic serving himself a beer for the first time in 13 years, thanks to advances made possible by primate research. Mustari ended by discussing the inspiring global outreach the WaNPRC performs under the directorship of Dr. Randy Kyes, Head of the Division of Global Programs at the WaNPRC.

Jason Goldman

Jason Goldman

Dr. Jason Goldman, an animal-researcher-turned-science-writer, rounded out the session by sharing lessons he’s learned from animals in communicating to a variety of audiences. Using brown-headed cowbirds and betta fish as examples of animals that change their messages based on who’s listening, Goldman said, “Animals have learned what I tell scientists over and over: Different messages are required for different audiences.” Goldman offered tangible pieces of advice for burgeoning (and established) science communicators, including 1) tell personal stories whenever possible and evoke emotion (using Cecil the lion as an example), 2) use simple visuals and avoid complex graphics (even popular infographics can be hard to digest), use to make your own memes to communicate science on social media (this is perhaps the easiest tip to pick up, as I was able to create my own – and first! – meme in about 30 seconds during his presentation), and 4) be relatable and make the public feel smart, not stupid.

The session concluded with a Q &A session from the participants seeking additional advice on best ways to communicate the importance of animal research to the public when you feel like your institution is resistant to the idea, how to deal with the internal struggle of loving animals while conducting research with them, and more. Given that the session went 20 minutes over its scheduled time, it was clear the audience found it an invaluable resource.

Later in the afternoon, Dr. Francis Collins, Director of the National Institutes of Health, gave a Special Presentation to SFN attendees in which he discussed recent advances in neuroscience with a particular emphasis on the BRAIN initiative. Though he rarely mentioned animal models in his talk, he did field anonymous questions from the audience afterward, one of which asked 1) what his personal opinion was on the role of animals, especially nonhuman primates, in the BRAIN Initiative, and 2) what concrete steps the NIH Directorship was taking to engage the public in the importance of animal research.

Collins stated that although the NIH worked with the Institute of Medicine to end chimpanzee research in the US, this “should not be seen as a reflection of how we feel about other nonhuman primates in research.”  He concluded by acknowledging the need for primates in some of the more invasive studies for the BRAIN Initiative that cannot be conducted in humans, and by underscoring the need for continued outreach to the public on the importance of animals in advancing biomedical research.

Amanda Dettmer

Amanda M. Dettmer, PhD, is a Postdoctoral Fellow at the Eunice Kennedy Shriver National Institute of Child Health & Human Development. Her writing does not reflect the opinions of the NICHD or the NIH.

Society for Neuroscience Today: Session on Animal Research and Public Outreach

Are you among the almost 30,000 neuroscientists are attending the annual Society for Neuroscience (SFN) meeting in Chicag0 this week?  Are you looking for a session aimed at building outreach and education efforts for better public understanding of animal research?  If so, SFN’s Committee on Animal Research has a session today at noon.

ME13  ANIMALS IN RESEARCH PANEL: Proactive Strategies to Increase the Positive Public Perception of Animals in Research.

Tuesday, Oct 20, 2015, 12:00 PM – 2:00 PM  N427

Panelists: Jason Goldman, PhD; Michael Mustari, PhD; Dario Padovan, PhD; Rolf Zeller, PhD

Description:  As scientists become increasingly visible and engaged with the public through blogs, citizen science, traditional media, and other outlets, there is also increasing interest in open communication to gain public support for animal research and to underscore its critical contribution to scientific and medical progress. This panel will answer questions like: How can scientists and organizations engage the public and speak effectively about animal research? What strategies and venues (both novel and time-tested) are being employed to engage different audiences and how can interested scientists learn and contribute? What challenges exist in this area and how are different groups addressing them?


Panelists include:

  • Prof. Rolf Zeller is a developmental geneticist that studies the molecular mechanisms governing organogenesis. He is a founding signatory of the Basel Declaration, by which researchers endorse the highest standards of ethically responsible animal research. He is the founding president of the Basel Declaration Society (BDS), an international grass-root organization dedicated to the Basel Declaration and actively promoting education on animal experimentation and the dialog with the general public, politicians and moderate critics.
  • Dario Padovan is the current president of Pro-Test Italia, which is an association that aims to promote and disseminate information about scientific research to the public. He was one of the founders of Pro-Test Italia and was the first chair of its Scientific Committee. He has masters degrees with honors in biological sciences, nutrition and dietetics, and bioethics.
  • Dr. Michael Mustari earned his Ph.D. in neuroanatomy from the University of Washington.  He is currently a Research Professor of Ophthalmology (UW). Dr. Mustari also serves as Director of the Washington National Primate Research Center (NPRC) at UW. He is responsible for providing scientific and administrative leadership to ensure an optimal environment for the care and well-being of nonhuman primates, which often provide the best animal models for studies of complex systems. All 7 NPRCs support the NIH mission of advancing scientific knowledge needed to develop new treatments and cures for diseases.
  • Dr. Jason G. Goldman is a science writer based in Los Angeles. He writes about human and animal behavior, wildlife biology, ecology, and conservation for various publications. He was editor of The Open Laboratory 2010: The Best of Science Writing on the Web, is co-editor of The Complete Guide to Science Blogging, and hosts a podcast called The Wild Life. He received his PhD at the University of Southern California.

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

Guest Post: Why science needs to improve

Jeremy BailooToday’s guest post is from Jeremy D. Bailoo, PhD, a developmental psychobiologist in the Division of Animal Welfare at the University of Bern, Switzerland. He is currently involved in research which examines the manner by which we house and care for animals and its relevance to animal welfare and how it affects experimental results. He is particularly interested in providing empirically based procedures for refining animal housing.

Why science needs to improve

In a recent article in the Huffington Post, Professor Marc Bekoff and Dr. Hope Ferdowsian outlined their reasons for believing that science does not need mice. Their article was written in response to an editorial in the New York Times which advocated for the need for female mice in laboratory research. Bekoff and Ferdowsian made a number of interesting points and cited relevant supporting literature. However, their response presented only certain aspects of the issues involved. In this piece I will deconstruct the arguments levied by both sides. I will refrain from critiquing information that was not accompanied by a citation in either article, as these constitute unsubstantiated opinion.

The authors of the New York Times editorial described a new study published in the journal Nature Neuroscience which suggested “that research done on male animals may not hold up for women. Its authors reported that hypersensitivity to pain works differently in male and female mice….If these differences occur in mice, they may occur in humans too. This means a pain drug…might appear to work in male mice, but wouldn’t work on women.” These authors then state that failure to consider gender or sex in research is well recognized and cite the work of Zucker and Berry (2010) as well as the repositioning of interests statement of the National Institutes of Health (NIH) specifying sex as a biological variable in NIH funded research (see here and here).

The NYT editorial framed a well-articulated argument and did not overstate any of the claims that it made. The issue of the underrepresentation of females in biomedical research has been repeatedly highlighted (e.g., here, here, here, here and here) with little change in US science funders’ policy until now. It is important to note that nowhere in this article is it stated that all research in mice is ungeneralizable to females. Indeed, whether a scientific result is generalizable to both sexes is dependent on the phenomenon being studied; and this seems to be the case in particular for pain research in mice.

Mice in a research laboratory. Image courtesy of Understanding Animal Research.

Mice in a research laboratory. Image courtesy of Understanding Animal Research.

In their argument against the use of mice in research in the Huffington Post, Bekoff and Ferdowsian state that “numerous experiments on male and female non-human animals (animals) fail to reliably hold up in humans, and many prominent researchers have argued we need to develop non-animal models in order to learn more about serious diseases from which numerous humans suffer.” It is without question that some (not all) experiments in male and female rodents fail to replicate their results when that same experiment is performed on humans. However, as the ability to falsify and to replicate an experimental result are the cornerstones of the scientific method, failure to replicate an experimental result does not imply poor generalizability of an animal model to the human condition. I have recently co-authored an article on this topic demonstrating that meta-analytic studies have revealed that the reporting of criteria related to experimental design and conduct in some biomedical animal experiments is poor. The reasons why the result of an experiment conducted in non-human animals may fail to be replicated in humans is a consequence of complex processes that cannot and should not be trivially summarized by the statement “we need to develop non-animal models in order to learn more about serious diseases from which numerous humans suffer.”

In support of their argument, Bekoff and Ferdowsian cite the article “Mice Fall Short as Test Subjects for Some of Humans’ Deadly Ills”. In summarizing this article, Bekoff and Ferdowsian imply that because C57BL/6 mice (a single strain of 16 classified as Tier 1 in priority for investigation) do not seem to be able to model sepsis in humans, then all mice fail as a model of human disease. This is a logical fallacy, and a quick google search leads to very interesting responses to this article. Some are in favour of this piece (e.g., here) while others quickly identify flaws with the logic (e.g., here and here). Indeed, in the original article, the authors state “The study’s findings do not mean that mice are useless models for all human diseases.”

Next, Bekoff and Ferdowsian make the claim that the former director of the National Institutes of Health, Elias Zerhouni has lost confidence in the use of mice to model anything that is related to humans (see here). Bekoff and Ferdowsian fail to cite the clarification or perhaps are unaware of the clarification that was given (see here) in which Mr. Zerhouni states, “In short, animal models remain essential to the basic research that seeks to understand the complexities of disease mechanism.” As my colleagues at the website Speaking of Research have put it: “Animal models are essential to developing new medicines. They are, obviously, not sufficient on their own – cell cultures, human studies and computer models (among others) are also crucial methods used alongside animal models.”

The next paragraph with a citation states “Even experiments involving similar nonhuman species have shown that studies in mice, rats, and rabbits agree only a little more than half of the time (please see Hartung and Rovida 2009)”. Careful reading of this citation, however, does not yield this information. Indeed, nowhere in this article are any of these claims made. More interestingly, the cited article states, “no acceptable alternatives to reproductive-toxicity testing (in animals, my emphasis) have emerged, or are likely to be validated by 2018. Computational approaches are also limited by the complexity of reproductive toxicity and because half of the REACH chemicals are mixtures, inorganic, salts or contain metal atoms, rendering toxicity less predictable”. Thus, rather than supporting Bekoff and Ferdowsian’s arguments, it would seem that Hartung and Rovida advocate for the use of animals in toxicological research because there are no good alternatives.


Laboratory mouse. Photo courtesy of Understanding Animal Research.

Bekoff and Ferdowsian then state, “Attitudes toward animals are also changing, and now is the time for action. As per a recent nonpartisan Pew Research Poll, a solid 50 percent of people surveyed now oppose the use of animals in laboratory experimentation — an all-time high in the public opinion research literature.” This is indeed alarming and is the reason I have spent many hours researching these data. It is time that active scientists speak up for their science and break the cycle of misinformation that is spreading throughout our society.

In their penultimate paragraph Bekoff and Ferdowsian indicate that many may be incredulous in realizing “that mice and rats aren’t animals but a quote from the federal register does in fact read, “We are amending the Animal Welfare Act (AWA) regulations to reflect an amendment to the Act’s definition of the term animal. The Farm Security and Rural Investment Act of 2002 amended the definition of animal to specifically exclude birds, rats of the genus Rattus, and mice of the genus Mus, bred for use in research” (Vol. 69, no. 108, 4 June 2004).” It is worthwhile to note the date of this citation, June 2004 – 11 years ago. Much has changed in those 11 years and much will continue to change in the future. As science progresses, the type of animals used in research, the manner in which they are used, and their care will be continually scrutinized by scientists and the public. As a result, animal care, use, and corresponding regulations will continue to be adjusted. Moreover, animals used in research (including birds, rats, mice) are covered by Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals since 1985 while guidelines for the care and use of laboratory animals have been critically considered since 1963 and have been continually updated as new information becomes available. Ferdowsian and Bekoff are either ignorant of current US regulations governing research or are deliberately being disingenuous.

These authors conclude that “there are numerous non-animal alternatives that are extremely reliable (please also see), and it’s about time they are used.” Again, where is the evidence for this? As I have outlined in this commentary, Bekoff and Ferdowsian have not provided sufficient evidence to come to this conclusion. Moreover, the statement that many non-animal alternatives are currently available and reliable requires careful deliberation. An example of such deliberation can be found here. The unsubstantiated statement that alternatives exist and are reliable does not make it so. Currently, such research and methods complement, rather than replace, research in non-human animals.

Thus, it would seem that the argument levied by Bekoff and Ferdowsian that science does not need research with mice is misleading. Poor reproducibility of experimental results is a problem in biomedical research. Indeed, it is a problem with science in general (e.g., here, here and here). To address the question “does science need mice”, one would have to: 1) examine the fields of science which use mice, 2) identify whether the science is performed with experimental rigour (design and conduct), and then 3) evaluate whether the findings obtained from these rigorous experiments are reproducible. By and large, the scientific community is still at step 2. As I mentioned previously, many fields which conduct research using mice report results that are irreproducible. The current cause ascribed to these failures is poor experimental design and conduct. This insight is gained by analysing whether information related to experimental design and conduct in published manuscripts and experimental applications are reported. For many fields of study employing the use of rodents, we cannot even begin to evaluate the effectiveness of a model because the manner in which the study was reported was poor. It is worth emphasizing that poor reporting of aspects of a study related to experimental design and conduct does not necessarily imply that a study was conducted poorly. Ascertaining this information would require interviews for each published article in question; a Herculean, if not impossible, feat. As highlighted in my recent paper, many solutions have been put forward to improve the manner in which we execute and report experiments but until these are endorsed and enforced, science in general will not improve. And that also applies to research using humans as subjects.

Jeremy D. Bailoo, Ph.D.

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

Guest Post: How do birds see the world?

Professor Aaron Blaisdell

Professor Aaron Blaisdell

Today’s guest post is from Professor Aaron Blaisdell and graduate student Julia Schroeder in the Department of Psychology at the University of California Los Angeles. Prof. Blaisdell’s area of research is animal learning and comparative cognition. He received his Ph.D. in Experimental Psychology and Behavioral Neuroscience at Binghamton University in 1999. Julia Schroeder is a graduate student in the Psychology Department at UCLA. This project is the basis of her dissertation research which she hopes to complete by May, 2016. She received a BS in Psychology at Whitman College where she compared rational decision processes in pigeons and humans. You can support their research through their crowdfunding campaign.

How do birds see the world?

How do birds fly around objects without crashing into them? Their object perception must be similar to ours, despite having a dramatically different brain and separate evolutionary history. Birds and mammals share a last common ancestor roughly 275 million years ago! Nevertheless, most birds and mammals, especially primates, rely on sight to navigate their world, find mates, avoid foes and predators, seek food and water, and care for their young.

Vision, both sensation and perception, has been one of the top areas of research in experimental psychology and neuroscience, going back to the visual psychophysics scientists of 19th century Germany. Visual perception and cognition is currently a dominant area of study in cognitive neuroscience. Much of what we’ve learned about human vision actually comes from research in nonhuman primates, especially the macaque monkey. This makes sense, since the human visual system is like that of just monkeys and apes.

One picture that has emerged is that, when we open our eyes, we see a world populated with objects. Our object-centered view of the world is also shared with the rest of the primates.

Pigeon in a test of comparative cognition.

Pigeon in a test of comparative cognition.

What about birds? They also navigate their world using vision. Flying puts high demands on the ability to rapidly detect and process visual information. The last thing a birds wants to do is to fly into an object because it couldn’t see it in time! This suggests that bird brains also engage in visual computational processes similar to that of the primate. But we currently don’t know much about how they do so. We want to know if birds solve the incredibly complex computational process of object perception the same way that primates do.

In our next research project, we plan to test whether bird brains handle object perception the same way that the human brain does. Pigeons will play a video game where they have to rapidly peck objects as they appear on a computer touchscreen located in a Skinner box. As soon as the object is pecked, a small food reward will be delivered to the pigeon from a hopper located below the screen. The faster the pigeons peck at the object, the sooner they get fed. The speed of their responses will tell us how the birds see the objects.

Specifically, we will show the pigeons four different objects, A, B, C, and D, one at a time (actual objects are different colored geometric shapes). The objects will appear in one of four locations on the screen (see a demo here). The objects will appear in a specific order that repeats. The locations in which the objects appear will also repeat. This will allow us to test how pigeons bind features into objects. If pigeons integrate features as humans and other primates have been shown to do, then they should learn that specific objects always appear in a specific location. This is called object-place learning. The object’s identity and location become bound as shared properties of a unique, coherent object. After the pigeons learn to play the game, we can then test for object-place learning by presenting special non-reinforced probe test trials. On these test trials, we will change the order of some of the objects, locations, or both.

Stimuli in learning sequence.

Stimuli in learning sequence.

Changing only the object or location should break the object-place association. Changing both together, however, preserves the object-place association, even though the sequence order has changed. If, like humans, pigeons bind object and location information together into perceptual memory, then changing only the object or the location order should be more disruptive than changing both!

What is life like for a laboratory pigeon?

Like all other vertebrates in research, housing and laboratory conditions for pigeons are well regulated. All research protocols go through the same stringent processes of review by the University’s IACUC, and the health and welfare of each pigeon is overseen by the Division of Laboratory Animal veterinarian staff. They receive the best possible care. In a typical pigeon laboratory, the pigeons are maintained as part of a flock in a vivarium. Birds are typically individually housed in large, comfortable cages, with constant access to water and grit. Feeding times are typically restricted to the afternoon after all subjects have completed their behavioral training. This keeps them motivated to work for food reinforcement in the operant chamber, and maintains subjects at a healthy weight similar to that of pigeons in the wild. Despite being housed in individual cages, the birds can see, hear, and smell the birds in the surrounding cages, thereby simulating a flock as it would be found in the wild. Unlike most mammals, or even parrots, pigeons do not engage in much touching or grooming of each other. Rather, pigeons in a flock hang out in close proximity to one another.

While some labs acquire wild-caught pigeons from their local area, we purchase ours from a vendor that breeds pigeons and other fowl for research purposes. Pigeons are a domesticated species, having lived in human environments since the dawn of agriculture in the Mediterranean region of Europe, Asia, and North Africa. Darwin was a known pigeon fancier, and bred pigeons as part of his own experimental investigations into the process of evolution by natural selection! To this day, there are pigeon fanciers and clubs around the world that breed pigeons for show, racing, and aerial acrobatics.

Why is this research significant?

The bird brain has a very different organization than the brains of humans and other mammals. Birds don’t have a visual cortex, for example. Thus, our research can lend insight into how a brain of such different structure solves the same computational process as does the mammalian brain.

Also, the brain of a pigeon is the size of your thumb! So how can birds, like pigeons, see objects the way that we do with far fewer neurons than in the human or monkey brain? Knowing how birds see the world can tell us a lot about what is unique about human vision, and what we share with other species.

Finally, we can also use our knowledge of how small bird brains efficiently create visual objects out of messy input to find new and powerful ways to build artificial visual systems for small mobile devices, such as drones and robots.

Many neuroscientists believe object perception is one of the most important and central processes of human vision. Nevertheless, object vision has been incredibly difficult to build into robot vision using AI approaches. Perhaps we can reveal the secrets to complex object perception in the small pigeon brain that will allow for breakthroughs in computer vision. This would be a huge win for human society!

Aaron Blaisdell and Julia Schroeder