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June 7, 2018   animal testing

 

EPA

Recently, as reported in Science  and other outlets, the Physicians Committee and People for the Ethical Treatment of Animals (PETA) found that in 2017, the first year of implementing the amended Toxic Substances Control Act (TSCA), the Environmental Protection Agency (EPA) required or requested roughly 10 times the number of animal tests for new chemicals as it had in previous years. In this post, we provide context on the circumstances leading to this alarming increase, explain how we uncovered it, and update you, our members and supporters, on what we are doing to reduce this inexcusably high number.

In June 2016, President Barack Obama signed into law the Lautenberg Chemical Safety Act, the first substantive amendment to TSCA in its 40-year history. The Physicians Committee and other organizations worked to ensure  that the law, which strengthened EPA’s ability to regulate industrial chemicals, would not result in a massive increase in animal testing.

In implementing the new law, EPA is required to determine whether new chemicals entering commerce pose unreasonable risks to human health or the environment. While EPA has long used human-relevant methods in its review of new chemicals—for example, predicting a chemical’s potential for toxicity based on its structural similarities to other, already characterized chemicals—it still requires chemical manufacturers to conduct animal toxicity tests in some situations. 

Because animal tests are not predictive of human health, a bipartisan group of senators and NGOs lobbied to ensure that language was included in the law that will, over time, reduce and ultimately replace the use of animals in chemical testing. As a result, the amended TSCA not only explicitly includes this historic goal but also provides the means to achieve it.

When requiring the development of new information, EPA is required to explain the basis for any decision requiring the use of vertebrate animals and to employ a tiered testing process, by which the results of screening-level tests—which use few or no animals—and assessments of available information inform its decisions on whether to require additional tests. Also, EPA and companies are required to consider and use scientifically appropriate nonanimal methods.

Finally, EPA is required to develop a strategic plan to promote the development and implementation of alternative methods and to report to Congress on its progress every five years. We have submitted extensive comments on this strategic plan a promising draft of which EPA released in March.

However, rather than wait for EPA’s first report, the Physicians Committee and PETA checked to see how much new animal testing EPA was requiring under its new chemicals review. We reviewed each consent agreement that EPA and chemical manufacturers entered into since EPA began implementing the amended TSCA in 2016. We were shocked to learn that in 2017, within these consent agreements, the agency required or requested 352 animal tests in which approximately 77,051 animals would be used.

It is important to note that it is very unlikely that all of these tests will be conducted. Most of EPA’s testing requirements are triggered by chemical manufacturers exceeding limits on time or production volume. If a manufacturer stops manufacturing before the time limit, or continues to manufacture the chemical below a certain volume limit, the tests need not be conducted. In addition to these testing requirements, EPA sometimes requests that manufacturers conduct tests in order to remove restrictions it has imposed on commerce. These “pended” testing requests can be reevaluated prior to the tests being conducted in case new information has become available which could prevent the test.

In 2017, a variety of animal tests were requested, including tests for skin sensitization and eye and skin irritation/corrosion—extremely painful tests on mice and rabbits for which acceptable alternatives exist. These tests would be conducted on numerous species of animals, including fish, guinea pigs, mice, rabbits, and rats. In contrast, in 2015, prior to TSCA reform, the agency required or requested only 27 animal tests for new chemicals, while in 2016, the number was 45. These tests would have used approximately 9,121 and 7,027 animals, respectively.

We immediately requested and received a meeting with top EPA officials to discuss the reasons for this alarming increase and steps EPA is taking to reduce its animal testing requests. At our meeting, EPA assured us that recently, it has begun relying more on “pended” testing requests than on triggered testing requirements, and this appears to be consistent with our preliminary review of 2018 consent agreements. However, we have so far found no adequate justifications for the decisions to require testing on vertebrate animals, which is required under the amended TSCA.

We also asked that EPA contact each company with which it entered a consent agreement to conduct animal tests for skin sensitization and inform it of EPA’s new policy to accept nonanimal tests, released in March of 2018. This action would prevent the deaths of hundreds of animals, and we are optimistic that EPA will take this step.

We continue to press EPA on these and related points and will update you on our progress in future blogs.

May 24, 2018   other

 

All of Us

Ever wonder how a person’s individual lifestyle, environment, and biological make-up can affect their health? The National Institutes of Health (NIH) is on a mission to find out.

Last week the NIH opened nationwide enrollment for their ambitious All of Us Research Program. The All of Us Research Program aims to engage one million participants across the United States to reshape the way people conduct research. This large-scale, longitudinal study will give researchers better insights into the biological, environmental, and behavioral influences that affect diseases. All of Us differs from other research studies in that it does not focus on a single disease or population. This research program will cover a variety of health conditions and will function as a national research resource for thousands of studies.

All of Us is a key component of the federal Precision Medicine Initiative (PMI). Precision medicine is an innovative method that takes into account individual differences in genetics, lifestyles, and environments to develop personalized care. The PMI intends to replace the “one-size-fits-all” approach to healthcare by bringing together researchers, health care providers, and patients to work together.

“The All of Us Research Program is an opportunity for individuals from all walks of life to be represented in research and pioneer the next era of medicine. The time is now to transform how we conduct research—with participants as partners—to shed new light on how to stay healthy and manage disease in more personalized ways. This is what we can accomplish through All of Us.”

—Francis S. Collins, M.D., Ph.D., director, National Institutes of Health

Many research studies lack depth and diversity, which restricts the generalizability of the results. All of Us aims to engage participants from “all walks of life”—it welcomes healthy and sick individuals of all backgrounds and regions of the country. By partnering with one million or more diverse volunteers across the United States, the All of Us Research Program will enable research to more accurately prevent and treat a range of health conditions, both rare and common. A research study this large will have the statistical power to detect associations between environmental and/or biological exposures and a wide variety of health outcomes. Anyone over the age of 18 who is living in the United States is eligible to sign up. Children will likely be able to join in the next few years.

Participants will be asked to give consent, agree to share their health records, and complete health surveys. Participants may also be asked for physical measurements and blood and urine samples. The samples will be collected at participating health care centers located throughout the country. Over the next ten years or so volunteers may be invited to share more data through health surveys, fitness trackers, or other research studies. Throughout the program, All of Us will share data and information with individuals. Participants can receive certain study results to help them know more about themselves. They may even get the chance to have their genome sequenced!

The All of Us Research Program is a human-relevant research study that is designed to improve human health. This program has the capability to alter research and healthcare in profound ways. Using human-focused methods, like this epidemiological study, paired with technological advances in research, is a step towards advancing human health through innovative research, while saving animal lives. All of Us offers numerous scientific opportunities. It has the potential to measure one’s risk for diseases based on genetic and environmental exposures, to identify why individuals respond differently to drugs, to develop new disease classifications and relationships, and to lead to advances in precision medicine. This type of scientific study could shape the way people conduct research far in the future—and that’s good for all of us.

 

Yesterday Physicians Committee toxicologist and vice president for research policy Kristie Sullivan, M.P.H., testified at two legislative hearings in Sacramento. Before the Assembly Committee on Environmental Safety and Toxic Materials, Sullivan described our support for AB 2474, which would require the California Department of Toxic Substances Control to review and, if appropriate, adopt two potential alternatives to a current live fish test it currently requires manufacturers to conduct on hazardous waste.

She also joined Social Compassion in Legislation and Lush Cosmetics to testify in support of SB 1249, the California Cruelty-Free Cosmetics Act, which would ban the marketing and sale of cosmetics that have been tested on animals in California.

Both bills successfully passed out of those committees. We’ll keep working on them as they move toward floor votes, so stay tuned for more details on how you can support these bills.


Physicians Committee Letterhead

AB 2474 Testimony

My name is Kristie Sullivan and I am a toxicologist, a California resident, and the vice president for research policy at the Physicians Committee. I have worked with experts to modernize testing protocols and regulations at the international, national, and state level for 15 years.

We support HB 2474 because it offers the DTSC the opportunity to assess advances in test method development and toxicology practice to take a more intelligent approach to toxicity testing.

Analyses have shown that daphnia are similar to fish, if a bit more sensitive, to toxic materials. The daphnia test is similar to the fish adult and embryo tests; groups of Daphnia pulex or magna are exposed to the test material and several dilutions and the number of “immobilized” daphnia are counted after 24 and 48 hours. The material is determined to be toxic if a certain percentage of daphnia fail to survive.

Daphnia are an important food source for fish and other aquatic organisms, making the daphnia toxicity test an indicator of potential effects of a waste on aquatic systems beyond the specific species of fish used in the current test.

In addition to consideration of the two test alternatives, we suggest implementing a tiered approach that takes the chemical characteristics of the waste into account in order to determine what, if any, testing should take place. This is now common practice in other regulatory jurisdictions.

In my opinion, the two tests are scientifically appropriate, and are likely to be adaptable for California’s need to ensure protection of aquatic life against a range of volatile, liquid, and solid wastes, while saving animals and state resources.

 


Physicians Committee Letterhead

SB 1249 Testimony

My name is Kristie Sullivan and I am a toxicologist, a California resident, and the vice president for research policy at the Physicians Committee.

In 1944 a test called the Draize rabbit eye test was created. This test involves placing chemicals in restrained rabbits’ eyes for 24 hours, then the animals are observed for signs of eye damage. If the test substance is a pressurized aerosol, the rabbits’ eyes are held open and the product is sprayed directly into the eye from about 4 inches away. Depending on the severity, rabbits experience pain, redness, swelling, discharge, and blindness. Rabbits were originally chosen because they do not produce tears, therefore unlike humans they cannot wash any of the product out of their eyes.

Fortunately, nonanimal methods based on human corneal, skin, immune, and other human cells and tissues are widely available to use in place of this and other tests. In fact, nonanimal methods for skin allergy perform better and are more accurate than the original animal test. Despite this progress, animal testing—including the Draize test—continues.

It is estimated that around 400,000 animals are killed worldwide each year to test cosmetics or cosmetic ingredients. In my experience, manufacturers conduct animal testing for a number of reasons, including institutional resistance, liability protection, regulatory expediency, labeling, or legal requirements. Policy initiatives—like this bill—are needed to ensure that cosmetics and personal care products sold in California are not tested on animals for any reason.

More than 35 countries have already enacted restrictions or bans on the testing of cosmetics or the marketing of animal-tested cosmetics. Citizens understand that animals shouldn’t suffer for the newest wrinkle cream or shampoo scent, and this bill creates that beautiful future.

April 25, 2018   Alzheimer's disease

 

Alzheimers patient with care giver

Alzheimer’s disease is the only one of the top ten causes of death in the United States without a disease-modifying treatment, so the United States has set a goal to find a way to effectively prevent or treat it by 2025 with the National Alzheimer’s Project Act (NAPA). The Physicians Committee for Responsible Medicine has been working tirelessly to advocate for the development and use of more human-based models and approaches in the search for a therapeutic intervention to change the course of Alzheimer’s disease (AD), and we are starting to make headway. Recent funding announcements feature support for human-relevant research.

In the last few decades Alzheimer’s disease research has been impeded by the use of animals as biological models, which produces results that do not accurately reflect human biology. As part of our work to right the course of research, this last January, we submitted another commentary to the NAPA Advisory Council to support replacing animal research with human-relevant models and methods for AD modeling and drug testing, as they have greater potential to predict human outcomes and produce therapeutic interventions that are less likely to fail in human clinical trials.

With Alzheimer’s research funding increasing significantly over the last few years with congressional support (the rest of this fiscal year alone—until September 2018—gets a $414 million boost), the National Institutes of Health (NIH), the world’s largest funder of biomedical research, continues to announce new Alzheimer’s research funding opportunities. The National Institute of Neurological Disorders and Stroke (NINDS) (the NIH institute which aims to understand how the brain and nervous system works and find treatments for neurological disorders) and the National Institute of Aging (NIA) (the primary NIH institute studying aging, longevity, and AD) are the two main federal agencies leading the implementation of these new research funds by creating funding opportunity announcements (FOAs) for the research community to apply for.  The National Advisory Neurological Disorders and Stroke Council (NANDSC), the Advisory Council to NINDS, recently approved six new research concepts for these FOAs, five of which are focused on human-based approaches. The NIH recently released FOAs to support these promising areas of research that may help pave the way to new treatments for Alzheimer’s disease and related dementias (ADRD).

Here is a brief description of the FOAs that support human-focused research:

  • Structural Biology of Alzheimer's Disease Related Dementias Proteinopathies (RFA-NS-18-015)

This FOA aims to characterize the differences between various pathogenic proteins (e.g., tau, alpha-synuclein, etc.) found in ADRD from human cell sources at the atomic level. These 3D pictures of the proteins can further the development of diagnostic tools and therapies for ADRD.

  • Pathway and Target Identification for Alzheimer's Disease Related Dementias (PAR-18-661)

This FOA aims to support the discovery and validation of new pathways, targets, and potential biomarkers related to the human biology of ADRD using bioinformatics tools and large-scale molecular platform analysis of brain tissue, human biofluid, and human induced pluripotent stem cell resources.

  • Planning Grant to Develop Phase III Clinical Trials for Lewy Body Dementia (RFA-NS-18-017)

This FOA aims to support the development of clinical trial teams to plan for phase III clinical trials testing treatments for patients with Lewy body dementias (LBD), which include dementia with Lewy bodies and Parkinson's disease dementia.

This FOA aims to create a collaborative, multidisciplinary, and possibly multi-national research group to systematically and comprehensively characterize pathological proteins (e.g., alpha-synuclein and amyloid-beta) present in human Lewy body dementia (LBD) post-mortem brain tissue and determine the mechanisms by which they cause toxicity and selectively kill certain brain cells.

  • Center without Walls (CWOW) for ADRD Radioligand Development and Testing (RFA-NS-18-025)

This FOA aims to create a collaborative, multidisciplinary, and possibly multi-national research group to develop molecular tools (radioligands) that would allow for the imaging of pathological processes associated with the human biology of ADRD so that they can be better diagnosed and monitored clinically. This research focus could support the synthesis and optimization of the radioligands, analysis of radioligands in human tissue, and first-in-human studies.

These human-focused research funding initiatives from the NIH will help shift the landscape of dementia research from focusing on animals to humans. If the NIH continues to invest in human-based rather than animal-based Alzheimer’s research projects, we may soon have an effective treatment to alter the course of this dreadful disease.

April 18, 2018   animal testing

 

we support organ donation

Organ and tissue transplantation saves more than 33,600 lives in the United States every year. But did you know that organ and tissue research also makes major contributions to saving and improving human lives? Donating organs and tissues to medical research is equally noble to donating for transplantation. Medical researchers need human organs and tissues to conduct ethical, efficient research and to achieve breakthroughs in medicine, ultimately saving and improving millions of lives.

National Donate Life Month was established by Donate Life America and its partnering organizations in 2003. This month, the Physicians Committee for Responsible Medicine is encouraging you to consider registering to donate your own tissues for research.  

Human organs and tissues are invaluable resources for medical research, diagnostic tests, biomarker discovery, drug development, product testing for safety or efficacy, and much more. Essentially every organ, tissue, and system of the human body is needed for research. Fresh intact organs and tissue samples are the most realistic model environment to conduct in-depth analyses of the human body. Human tissues are used in research and development across the full range of human biological systems, including cardiovascular, neurological, reproductive, digestive, excretory, hepatic, dermal, ocular, respiratory, immunological, metabolic, and endocrine systems research.

Numerous scientific discoveries would not have been possible without the use of human organs and tissues for research. Through brain donation, scientists discovered that male children with Autism Spectrum Disorder (ASD) have abnormally high levels of neurons in the region of the brain associated with emotional, social, cognitive, and communication development. An excess of neurons in any part of the brain can lead to abnormal brain function and development.1 Due to their physiological differences, animals do not develop ASD, which is one of the many reasons why researchers need to adopt human-relevant research methods. This finding impacts the way scientists study ASD, research that wouldn’t be possible without donation.

Another study using donated brain tissue found that people with Major Depressive Disorder (MDD) had lower expression of genes related to how brain cells communicate in the brain region associated with working memory and decision-making function compared to their healthy counterparts. The lower expression was observed for genes that are involved in synaptic function. When this is disrupted it may contribute to behavioral fluctuations, like those detected in people with MDD.2 This study increased scientists’ knowledge of the biology of MDD and allowed researchers to develop methods to stabilize gene expression, which may be more effective than current anti-depressive treatments.

Other monumental discoveries made using human tissues include the development of vaccines such as polio, chicken pox, rubella, and shingles. Advances in stem cell therapy can also be contributed to tissue donation. Researchers have learned how to reprogram human cells from donated tissues and make them into induced pluripotent stem cells. These cells can develop into neurons or other body cells that researchers can cultivate in labs to better understand diseases, such as Alzheimer’s disease.

Organ and tissue transplants take precedence over any other need. The circumstances of death and the medical history of the donor, however, determine suitability for transplantation. Medical professionals ultimately decide whether organs and tissues are suitable for transplantation. If organs and tissues are not viable for transplant, donation for research and education provides another option for willing donors and donor families to save human lives.

Most people can donate for medical research and education. Age and medical condition is not a barrier. Often times, a medical condition that might make someone an unsuitable organ or tissue transplant donor may be the exact thing a researcher needs to carry out an important study. There is no cost to the donor or donor family, and deceased donations may not interfere with funeral arrangements.

There are many options available for those who wish to donate their tissues to research. Below is a non-exhaustive list of reputable donation organizations. Tissues for rare diseases are in high demand. Research tissue donation agencies in your area for more information.

Donate Life America
Organ, eye, and tissue donation for transplantation

Donate Life America is nonprofit organization leading its national partners and Donate Life State Teams to increase the number of donated organs, eyes, and tissues available to save and heal lives through transplantation, while developing a culture where donation is embraced as a fundamental human responsibility.

National Disease Research Interchange
Organ and tissue donation for research

The National Disease Research Interchange (NDRI) is a not-for-profit organization that serves as a Human Tissue and Organ for Research Resource. It provides human tissues to scientists in academic, corporate, and independent research organizations throughout the world.

NDRI has been supported by the National Institutes of Health (NIH) for more than 30 years. Their tissue recovery network includes over 130 partners comprised of organ procurement organizations, eye banks, tissue banks and hospitals. Their biorepository facility is accredited by the College of American Pathologists. NDRI connects scientists with anatomical structures, organs, and tissues with annotated data to support research across the full spectrum of disease and disability.

Brain Donor Project
Brain donation

One out of every six people is suffering from a devastating neurological disorder or disease. That’s why brain donation is critically needed. The NIH NeuroBioBank has partnered with The Brain Donor Project to help potential donors register for brain donation. The Brain Donor Project is a nonprofit organization that aims to increase the supply of human post-mortem brains donated for scientific research.

Science Care
Whole body donation

Science Care is the world’s largest accredited whole body donation program. Science Care works with medical schools, research hospitals, and medical device companies to help support the training of physicians and surgeons and to assist with the development of new medical products, procedures, and treatments.

The gift of body donation through Science Care has contributed to the advancement of treatments for conditions such as Alzheimer’s disease, cancer, diabetes, multiple sclerosis, amyotrophic lateral sclerosis (ALS), arthritis and degenerative joint disease, spinal injuries, hip replacement surgery, infectious diseases, heart disease, and much more.

Pattern.org
Tumor donation

Pattern.org was launched by the Rare Cancer Research Foundation, a non-profit dedicated to curing rare cancers through collaborations that conduct effective research and accelerate deployment of promising therapies. Pattern.org enables cancer patients to directly donate their tumor tissue and medical data to high-impact research projects. In this way, Pattern.org empowers patients to be directly involved in cancer research.

Mayo Clinic
Whole body donation

Mayo Clinic's anatomical gift program accepts whole-body donations for the purposes of medical education, research and surgical training, and the development and testing of new surgical devices and techniques. Body donation plays a critical role in helping medical and health-related science students master the anatomy of the human body and provides researchers with an essential tool for medical discoveries.

References

  1. Courchesne E, Mouton PR, Calhoun ME, et al. Neuron number and size in prefrontal cortex of children with autism. JAMA. 2011;306(18):2001–2010. doi:10.1001/jama.2011.1638
  2. Kang HJ, Voleti B, Hajszan T, et al. Decreased expression of synapse-related genes and loss of synapses in major depressive disorder. Nature medicine. 2012;18(9):1413-1417. doi:10.1038/nm.2886.

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