Good Science Digest

The Physicians Committee
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Good Science

March 3, 2017  

 

Toxicologists study the effects of chemicals, drugs, and other products to assess potential harms to human health or the environment. The Physicians Committee promotes the use of nonanimal toxicological test methods, because they can be faster, more cost-effective, and human-relevant, and will allow us to collect much more information than we can currently using expensive, slow animal tests. 

The Society of Toxicology (SOT) annual meeting is the world’s largest gathering of toxicologists, and the Physicians Committee actively participates every year. Last year, we presented on Adverse Outcome Pathways as part of a continuing education session and held a hands-on training on the same topic. Adverse Outcome Pathways are a framework to collate information on how chemicals affect biological systems (like cells, tissues, and organs) and support the development of predictive nonanimal tests.

This year, the meeting will be held March 12-16 in Baltimore, Md, we are again hosting or co-sponsoring multiple events to engage and train toxicologists and regulatory scientists with scientific and policy initiatives to replace animal tests with more human-relevant methods. These include stakeholder discussions of progress in reducing or replacing pesticide lethal dose and skin irritation tests, regulatory reform of the pharmaceutical sector, and a four-hour training on the use of “read-across” to predict the toxicity of certain chemicals based on their chemical structures. 

Here’s a select list of Physicians Committee-sponsored ancillary meetings or events. If you are attending SOT, we invite you to attend or contact Kristie Sullivan (ksullivan@pcrm.org) for more information.

Download a curated list of other SOT scientific sessions and events of interest to scientists working with in vitro and computational methods.

Sunday, March 12
Read-Across: Case Studies, New Techniques, and Guidelines for Practical Application
1:15-5:00 PM
Baltimore Convention Center
Chairpersons: Kristie Sullivan, Physicians Committee for Responsible Medicine & Mark Cronin, Liverpool John Moores University

Abstract: The relationship between structure and activity has been exploited in the hazard characterization of chemicals for several decades, including specifically the practice of “reading across” or applying toxicity data from one or more chemicals to another with a similar structure to fill a data gap. Read-across is currently a useful strategy to increase our understanding of chemical hazard without de novo testing. However, expertise, application, and acceptance of the results of a particular read across vary within and among organizations and geographical regions. There are a number of reasons for this, including regulatory or legislative drivers, an increasing motivation to expand the use of non-testing strategies, and minimal consensus around how to weigh evidence and address and express uncertainty. Recently, multiple stakeholder organizations have contributed to active and robust discussions on read across in a variety of venues in an effort to build consensus around these issues. This course will update participants on those efforts and provide practical guidance for conducting read-across for regulatory use, including across different regulatory regions. Speakers will present experience-driven case studies to share best practices and communicate the state-of the-art for structure-based read-across, while looking ahead at how results from New Approach Methodologies including in vitro, “omics,” and high throughput/content methods may be incorporated into a read across to improve its outcome.

Tuesday, March 14
Hands-On Seminar: Creating an Adverse Outcome Pathway in the AOP Wiki
5:00-7:00 PM
Hyatt Regency Baltimore
Constellation Ballroom A

Deepen your understanding of the AOP Wiki and gain experience entering an Adverse Outcome Pathway in a structured, hands-on seminar Tuesday evening.

Version 2.0 of the AOP Wiki was released in November 2016, and this seminar will be ideal for those wishing to gain some hands-on experience with the new version as well as those who are new to the AOP concept.

See full agenda and please register in advance to ksullivan@pcrm.org.

Wednesday, March 15
Driving Innovation in Preclinical Pharma Testing: Takeaways and Opportunities Following the 2017 Preclinical Innovation and Patient Safety Roundtable
6:45-7:45 AM
Hilton Baltimore
Room Tubman A

DiscoverX and the Physicians Committee for Responsible Medicine invite you to join us for breakfast and discussion on improving preclinical testing through scientific innovation, regulatory updates and training. 

On January 11, 2017, stakeholders from federal agencies, the pharmaceutical industry, academia, health, research and patient organizations, and technology companies attended the Preclinical Innovation and Patient Safety Roundtable to discuss scientific, legal and training issues that stifle preclinical innovation and negatively affect patients. This meeting will highlight key takeaways and recommendations for next steps.

Please RSVP to ebaker@pcrm.org.

Alternative Approaches to Systemic and Topical Toxicity: Making Progress on the EPA OPP Six-Pack
5:00-6:30 PM
Sheraton Inner Harbor
Loch Raven room

This open stakeholder discussion will feature presentations and discussions highlighting work to reduce and replace in vivo testing for the “six-pack”, a set of six acute systemic and topical toxicity tests required by the EPA Office of Pesticide Programs for pesticide active ingredients and formulations. These tests include: acute oral, dermal, and inhalation toxicity, skin and eye irritation, and skin sensitization. 

The evening will focus on two specific elements of this ongoing work: 1) a pilot effort to reduce formulation testing using the GHS Additivity Equation for acute systemic toxicity, and 2) in vitro methods for skin and eye irritation. Ongoing work to provide predictive analysis of the in vitro methods and necessary next steps will be discussed.

The participation of all stakeholders wishing to learn more or get involved is highly encouraged.

February 24, 2017  

 

How do we know if we’re succeeding? It’s a question we are always trying to answer. If we want to improve research and testing by reducing animal experiments, we need to know how many animals are used in laboratories. But we don’t.

Rough estimates of how many animals are used in United States laboratories are as high as 100 million annually, but we have little idea whether that number is accurate. More importantly, we have no idea whether that number is going up or down. This lack of clarity can largely be blamed on a problem unique among industrialized nations – namely, our only federal law designed to regulate the use of animals in labs excludes from the definition of “animal” more than 90 percent of animals used in labs. Most rats and mice and all birds and cold-blooded vertebrates are not covered by the Animal Welfare Act.

For the small percentage of animals covered by the Animal Welfare Act, each research facility must send the U.S. Department of Agriculture (USDA) an annual report listing the number of animals used, categorized by species. Unfortunately, the use of these reports as a monitoring system hit a major snag earlier this month, when the USDA abruptly shut down its animal welfare database.

While the online database was very useful, even when research facilities’ annual reports were available, it’s not clear how much the numbers could be trusted. Under the Animal Welfare Act, every U.S. research facility must have an Institutional Animal Care and Use Committee, which is in charge of evaluating proposed requests for animal use and ensuring legal standards of animal care and husbandry. These committees are the primary entity in charge of compliance with federal law, but according to a USDA audit,over a three-year period ending in 2011, almost half of all them were found to be in violation of the law. One of the primary reasons for the committees’ 1,379 Animal Welfare Act violations over that time was that the groups “did not recognize the importance of submitting an accurate annual report.”

Compare the U.S. system to that of the European Union, where all vertebrates (including rats, mice, birds, and fish) and even octopuses and squid are covered by the region’s law on animal use for scientific purposes. That law also results in the collection of information on not only how many animals and what species are used in experimentation each year but also where the animals originate and for what purpose they are used (broadly speaking). This information, which has been published every three years by the EU in a public report, shows that between 2008 and 2011 the number of animals decreased by more than a half-million. Under a new law, the next report, including even more detail, will be published in 2019. If we had similar information in the U.S., we could know if efforts to reduce animal experimentation are succeeding or failing and which efforts are most successful.

On this side of the Atlantic, how do we get closer to a more transparent system? The best step might be to reverse the 2002 congressional action that changed the Animal Welfare Act’s definition of “animal” to exclude the species mentioned above. That’s unlikely given the current divisiveness on Capitol Hill. However, Republican Rep. Ken Calvert of California and others are trying at least to require that more information about the federal government’s use of animals in testing be made available to the public.

In addition, three scientists at Hannover Medical School in Germany think they might have one answer to this problem of transparency—registries of animal studies, which could include details of each experiment and animal numbers. As the journal Science reports, these registries would address the problem that half of all animal experiments are never published in scientific journals. In contrast to the dearth of publicly available numbers on animal studies, the U.S. Food and Drug Administration already mandates that researchers preregister human clinical trials online.

Ultimately, whatever the system of transparency, it’s clear more is needed. Unless the shutdown of USDA’s animal welfare database is either reversed by the agency or overturned by a court, organizations like ours will be forced to wait months or years to receive records via federal Freedom of Information Act requests, and  may have to bring separate lawsuits against the USDA to obtain the information. Meanwhile, numbers for most animals used in U.S. laboratories aren’t available from any central repository. The federal National Institutes of Health funds approximately $13 billion worth of animal experiments each year. The public deserves to know how that money is spent, and whether we are moving in the right direction—away from animal research.

 

February 17, 2017  

 

A Need to Change Clinical Research Approaches in Studying Alzheimer's Disease

Alzheimer’s disease is the most common form of dementia, affecting more than 5 million Americans. This number is expected to triple in prevalence by 2050, which is estimated to quadruple health care costs to $1 trillion.

To prevent this oncoming public health crisis, in 2011 Congress passed the National Alzheimer’s Project Act (NAPA) to create a national strategic plan coordinating the federal government’s efforts to treat and prevent dementia. An Advisory Council on Alzheimer’s Research, Care, and Services, consisting of members from relevant federal agencies and nongovernmental organizations, meets quarterly to evaluate progress, update the strategic plan, and make recommendations to Congress.

At the Council’s Feb. 3 meeting, Physicians Committee scientist Feng-Yen Li, Ph.D., delivered a public commentary to outline impediments to progress to find an effective intervention to treat or prevent Alzheimer’s disease. For example:

  • Drug candidates are initially tested in animal models that do not recapitulate the human disease, unlike human-based models, which are derived from patients or patient data.
  • Patients with chronic health conditions (e.g., diabetes, cardiovascular disease) that often occur alongside the most common form of Alzheimer’s disease are often excluded from participating in clinical trials, which means important underlying factors may be overlooked and the drugs may fail to work in these patients.
  • Drug targets for clinical trials are often based on genetic defects or pathways characterized in the rare inherited form of Alzheimer’s but are tested in patients with the common form of Alzheimer's who may or may not have genetic risk factors.
  • Alzheimer's drug development is often focused on reducing the signs of pathology such as brain plaques. However, these may just be a consequence rather than a cause of the disease. Little focus is on the underlying lifestyle risk factors of the disease.

Dr. Li strongly recommended the Council direct future funding and research efforts in Alzheimer’s disease to clinical trials based on data derived from humans or human-based models and focused on modifying lifestyle risk factors such as diet. A copy of the full commentary is available here.

To further promote these concepts, the Physicians Committee’s Ann Lam, Ph.D., has organized a discussion panel on Shifting Perspectives on Dementia, Science, and Health Policy at the 2017 American Association for the Advancement of Science meeting, featuring three experts in Alzheimer’s prevention research: Drs. Rhonda Au, a professor at Boston University; Jessica Langbaum, an associate professor at the Banner Research Institute; and Neal Barnard, president of the Physicians Committee.

February 13, 2017  

 

UPDATE – March 7: USDA has begun to release small amounts of information previously removed from its website. However, the online database remains down, and the vast amount of previously searchable information is still accessible to the public only through time-consuming FOIA requests. The Physicians Committee continues to pursue its lawsuit and work with allies in Congress to restore the database.

On Feb. 3, 2017, without warning, the U.S. Department of Agriculture (USDA) shut down its publicly available animal welfare database, known as the Animal Care Information System. This will make it harder to find out how animals are used in laboratories and whether those facilities are complying with federal law. Without this information, it will be dramatically more expensive and time-consuming to track whether researchers are moving away from animal experiments and toward human-relevant studies.

The database included inspection reports of research facilities, testing laboratories, and other institutions regulated under the federal Animal Welfare Act and Horse Protection Act. The database also included research and testing facilities’ annual reports, which allowed the public to see how many Animal Welfare Act-covered animals were used, organized by species.

We have filed a federal lawsuit in an effort to restore the database. You can also help by contacting your members of Congress.

In recent years, the Physicians Committee has used records from the USDA database to close a notorious primate research center, to end a university’s use of cats in a potentially painful medical training exercise, to support the eventual end of chimpanzee experimentation in the United States, and achieve many other advancements in medical research and training. Here are just a few key examples:

Harvard University’s New England Primate Research Center Closes

A 2011 Physicians Committee report detailed how a primate (later revealed to be a highly endangered cotton-top tamarin) was found dead in a cage at the Harvard facility after going through a machine that uses near-boiling water and caustic chemicals to wash cages. Later, we helped reveal other accounts of animal deaths and mistreatment, including a monkey dying after receiving an overdose of anesthetics and a cotton-top tamarin dying of dehydration because staff failed to place a water bottle in his cage. Records from these incidents provided grounds for a federal Endangered Species Act complaint because Harvard was negligently harming and killing cotton-top tamarins, a critically endangered species. In May 2015, Harvard closed the New England Primate Research Center for good.

University of Virginia Ends Use of Cats for Pediatrics Training

In 2010, the Physicians Committee launched a national campaign to end the use of live cats in the teaching of pediatrics residents at the University of Virginia (UVA). Physicians-in-training at UVA would repeatedly force breathing tubes down the throats of cats, a procedure that can cause tracheal bleeding, scarring, and severe pain. This was being done despite the widespread availability of human-relevant training methods modeled on human anatomy. Records obtained via the USDA database showed that the supplier of cats to UVA—Liberty Research in Waverly, N.Y.—habitually provided kittens with half as much space as required by the Animal Welfare Act during shipping to facilities like UVA. The company was cited 11 times in just an eight-month period for violating this section of the law. Sending these records to reporters helped generate media coverage and drive people to an online petition that gathered more than 185,000 signatures urging UVA to modernize its medical training. In 2013, UVA made the decision to end animal use and adopt the remaining cats to homes.

Chimpanzee Experiments End in the United States

In 2010, we discovered that the National Institutes of Health (NIH) was planning to transfer 186 chimpanzees from semi-retirement to a research facility in San Antonio, Tex. However, the USDA database revealed that the facility—the Southwest National Primate Research Center—had violated the Animal Welfare Act more than 30 times in five years. Using this information, we filed numerous federal petitions and brought the information to the attention of media outlets and members of Congress. That exposure was an important part of a broad campaign by the Physicians Committee and other organizations, which ultimately halted the chimpanzees’ transfer. It also served as the beginning of the end of chimpanzee experimentation in the United States. In 2015, after years of work, NIH announced that the last chimpanzees kept in reserve would be retired to sanctuary, along with the hundreds previously retired from experimentation by the agency. Had the database not been available, we would have been forced to file Freedom of Information Act requests that would taken months—possibly even years—to fulfill.

NASA Cancels Plans to Irradiate Monkeys

In November 2010, the National Aeronautics and Space Administration (NASA) announced plans to irradiate squirrel monkeys in a misguided attempt to learn the effects of deep-space radiation. Due to the basic anatomical and physiological differences between humans and squirrel monkeys (who weigh less than 2.5 pounds), these experiments were destined to fail. The Physicians Committee used records from the USDA database to reveal repeated violations of the Animal Welfare Act at the two laboratories where the experiments were to be conducted. These violations included multiple failures to ensure that procedures were in place to limit discomfort and pain in animals—a basic rule of the law. Using these documents and working with members of Congress, former researchers, and even a former NASA engineer who resigned her post in protest, we were able to halt the experiments before they began in little more than a year. The effort sent a strong message to NASA that it must more carefully consider the lack of scientific evidence for using animals in experiments.

These examples are just the tip of the iceberg. The Animal Care Information System is vital to understanding whether facilities regulated under the Animal Welfare Act are in compliance with the law and whether the USDA is carrying out its obligations under that same law.

We are working hard to restore the database. You can help by contacting your members of Congress.

January 26, 2017  

 

Welcome to Good Science, the Physicians Committee’s new digest covering obstacles to and advances in 21st-century technology that will improve human health.

In this “inaugural” post, Physicians Committee scientists give President Donald Trump five policy recommendations to advance human health research during his administration.

  1. Improve Medical Care for U.S. Troops by Directing the Department of Defense to Phase out Animal-Based Training 
    Outgoing Republican congressman and military physician Joe Heck has called for the U.S. military to stop shooting and stabbing animals to teach combat trauma procedures. Troops would be better served if medical personnel were trained on human-based simulators instead of goats and pigs. More >
     
  2. Double Down on Innovative Research Programs
    Guiding our nation’s health research to make progress on today's major challenges requires vision and creativity, and director Francis Collins, M.D., Ph.D., has been supportive of some of the most innovative programs at the National Center for Advancing Translational Sciences, including the Tissue Chip for Drug Screening and Toxicology in the 21st Century programs. Additional investment should be directed towards similar research projects. More >
     
  3. Ensure 21st-Century Consumer Safety by Creating a Roadmap to Replace Animal Tests for Chemical Testing
    Testing chemicals, cosmetics, and other products using animals is cruel, and it isn't keeping us safe. Scientists have created—or are developing—advanced test methods based on human biology, but current laws and regulations across different agencies can prevent new methods from replacing the old ones. We need an authoritative, clear roadmap to coordinate multiple government and private sector efforts, streamline regulations, and save resources. More >
     
  4. Revolutionize Medical Research by Directing Research Funds Toward Human-Relevant Models
    We have spent trillions of dollars on cancer, diabetes, and Alzheimer's disease research, and we have not gotten our money’s worth. Research with animals—mice, rats, dogs, sheep, monkeys—doesn't translate. We need to focus this money on human-relevant research methods: clinical and epidemiological research, human cell and tissue models, and computer-driven data analysis and simulation, to understand, prevent, and cure these human diseases. More >
     
  5. Spur Innovation and Lower Drug Development Costs by Directing the FDA to Reform Preclinical Tests
    FDA regulations limit innovation by mandating preclinical animal tests, even where more predictive human-relevant tests exist. Industry and patients would benefit from more efficient, timely and predictive preclinical pharmaceutical tests. More >