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The Physicians Committee

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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.
Tumor donation 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. enables cancer patients to directly donate their tumor tissue and medical data to high-impact research projects. In this way, 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.


  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.

March 26, 2018   organ on a chip


The Physicians Committee is posting a series of informative articles to provide readers a more in-depth understanding of human-relevant research models. This occasional series will provide readers with more information about how new technologies promise to revolutionize scientific research, product testing, and even medical education. Scientists working on these technologies are pioneering a more ethical and effective approach—and we can’t wait to tell you more.

Microengineered Organ-Chip is made out of a flexible polymer that features tiny channels that can be lined with thousands of living human cells. Image credit: Emulate, Inc.

Microengineered Organ-Chip is made out of a flexible polymer that features tiny channels that can be lined with thousands of living human cells.

Image credit: Emulate, Inc.

Is the Pepto-Bismol theme song the anthem to your life? You aren’t alone! Digestive diseases affect 25 percent of the United States population, yet there are few treatments available to help. The human intestine-on-a-chip (Intestine-Chip) technology may help ease your gastrointestinal (GI) system by revolutionizing our understanding of digestive diseases and paving the way for future treatments.

The gastrointestinal system is responsible for the breakdown of food and liquid into nutrients for the body to absorb and use for energy, growth, and cell repair. The bacteria in the intestine—the gut microbiome—plays an important role in digestion. Microbes aid in the metabolism of food, the production of certain vitamins (like vitamin K), and are essential for immune function and overall health. Many drugs that are ingested orally can affect the delicate equilibrium of the microbiome. An Intestine-Chip model can help illuminate how to protect the microbiome.  

Scientists from Cedars-Sinai Medical Center and Emulate, Inc. have bioengineered a new Intestine-Chip. This innovative in vitro (cell culture) model combines the microfluidic organ-on-a-chip technology with organoid-based methods by incorporating human cells onto a microengineered chip about the size of a USB stick. This IntestineChip is created using blood and skin cells that are reprogrammed into induced pluripotent stem cells, which can produce any type of cell. Using special proteins and other substances, the cells are able to generate into organoids or three-dimensional mini organs.

The chips are created by casting an upper and lower layer with microfluidic channels, using a flexible polymer with a silicon membrane in between. The layers are united together using plasma bonding to form the complete chip. The cells are then seeded into the channels to form the intestinal lining. This Intestine-Chip is unique because it can replicate many anatomical functions of the human intestines. It has to ability to simulate physiological fluid flow and peristalsis-like motions, which allow scientists to analyze the intestinal physiology and pathophysiology as they would inside the human body. This chip offers insight into the biological mechanisms of the intestinal epithelium, the layer of cells that forms the lining of both the small and large intestine and which plays a major role in many GI diseases.  

The Intestine-Chip‘s ability to accurately replicate the human intestinal epithelium has the potential to drastically improve treatments for the millions of people who suffer from debilitating GI diseases such as Crohn’s Disease, inflammatory bowel disease, and ulcerative colitis. Since these chips can be developed using a person’s own tissue, they have the potential to set a new standard for personalized medicine. Rather than testing numerous drugs on animals, which may be costly and ineffective, or in a living patient, scientists could use a patient’s own cells to develop a personalized Intestine-Chip. Different drugs can then be tested in the chip to determine which treatment is best for each individual patient. This human-relevant system is a promising alternative to unsuitable methods using animals, can be used for drug discovery, and will lead to safer and improved treatments. This is a monumental technology that will improve researchers’ understanding of how medicines, diseases, and foods interact with a person’s microbiome and affect an individual’s health. 

Recent news reports indicate that at least two pharmaceutical companies, Roche and Takeda, have partnered with Emulate to use the organ chips in drug discovery and development. Roche will use the chips in place of animals to run drug safety and efficacy tests. Takeda will use the Intestine-Chip to discover and evaluate GI disease drugs and biomarkers.

Link to article:

Workman MJ, Gleeson JP, Troisi EJ. Estrada HQ, Kerns SJ, Hinojosa CD, et al. Enhanced utilization of induced pluripotent stem cell-derived human intestinal organoids using microengineered chips. Cellular and Molecular Gastroenterology and Hepatology. 2017.


Following the news that the National Institutes of Health (NIH) budget has increased by $3 billion for fiscal year 2018, the Physicians Committee wrote to NIH director Frances Collins, urging Collins to use the additional funds to prioritize human-relevant research. Read the letter below:

Physicians Committee Letterhead

March 23, 2018 

Dr. Francis Collins
Director, National Institutes of Health 9000 Rockville Pike
Bethesda, Maryland 20892 

Dear Dr. Collins, 

I am writing on behalf of the Physicians Committee for Responsible Medicine and our membership of more than 12,000 physicians and more than 175,000 other medical professionals, scientists, educators, and supportive lay members about increased funds provided to you in the recent fiscal year 2018 (FY18) Labor, Health and Human Services, and Education funding bill. We recommend that you invest this additional $3 billion in human-relevant research, not animal research. 

The National Institutes of Health (NIH) is the nation’s leader in biomedical research and has the potential to fund groundbreaking discoveries to improve health and save lives. As you are aware, animal studies are costly, time-consuming, and often poorly predictive of human health. With a continuously growing population in the United States and new and emerging health issues always on the horizon, changes in our approach to research funding are urgently needed. 

Currently, thousands of diseases affect humans that do not have effective treatments. Yet, new drugs take over 10 years to develop, typically cost more than $2 billion, and have a 95 percent failure rate in human clinical trials. Animals will always have physiological, anatomical, and genetic differences from humans that will impede the translation of research findings derived from animal biology. It is time to invest more in the development and application of human-based methods. We recognize that NIH is beginning to invest more in human-relevant models via the National Center for Advancing Translational Sciences and other initiatives; however this investment pales in comparison to the amount put towards animal research. We must shift this balance. 

This bill allocates $1.8 billion for Alzheimer’s disease research, which is the only top-ten chronic disease without an effective intervention for treatment or prevention. Today, 5.3 million Americans suffer from Alzheimer’s, and this number is expected to triple by 2050. At present, Alzheimer’s research relies on animal models, despite the fact that 99.6 percent of Alzheimer’s drugs that appear successful in animals fail in human trials, and it is known to scientists that animals do not develop the disease to the same capacity as humans. Rather than misusing the supplementary $414 million that is being allocated to Alzheimer’s research for FY18 on ineffective animal research, it should be devoted to efficient, human- relevant research. 

There are many humane and reliable human-relevant methods that are already being used to conduct scientific research and regulatory testing. Organs-on-chips and the multi-organ body-on-a-chip are cutting edge platforms that can significantly advance drug and toxicology screening and open the door for personalized medicine. Human-derived stem cells are redefining research by improving scientists’ understanding of how diseases progress and allowing the development of therapies for regenerative medicine. Three-dimensional bioprinting has made enormous advances, allowing the expansion of new therapies and diagnostics. This technology has the potential to one day manufacture custom-made organs. 

Adequate funding and support is severely needed to increase the development and application of these technologies. Investment in human-relevant methods should be prioritized over unhelpful and ethically questionable “humanized” mice and animal-human chimeras. In addition to funding extramural investigative research using human-relevant models, we suggest NIH consider other strategies to support a transition away from animal research. For example, increased resources and incentives could be provided to allow easier access to human tissues for research, grant applications featuring human- relevant models could be “fast-tracked” for approval, and specific calls for proposals could specify human-relevant models. 

We urge NIH to take this opportunity to increase its funding of groundbreaking human-relevant research, making research more ethical and effective and improving public health. Thank you for your attention to this urgent and important matter. 


Janine McCarthy, MPH Research Policy Specialist 

Kristie Sullivan, MPH Vice President for Research Policy

March 1, 2018   animal testing


It’s that time of year again! The Society of Toxicology (SOT) annual meeting—the world’s largest gathering of toxicologists—is taking place March 11-15 in San Antonio, Texas. Just like last year, Physicians Committee scientists are actively participating in sessions throughout the conference to advance their work in promoting more effective, nonanimal toxicological test methods. 

We are again sponsoring events to engage and train toxicologists and regulatory scientists with scientific and policy initiatives to replace animal tests with more human-relevant methods, including our Adverse Outcome Pathway seminar. We are also participating in multiple poster sessions to inform attendees of current topics in predictive toxicology and alternative test methods. 

Here is a select list of Physicians Committee-sponsored sessions or events. If you are attending SOT, we invite you to attend these sessions. Please contact Kristie Sullivan ( for more information. 

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

Monday, March 12

Poster Session:  Regulatory Policy and Policy Evaluation

The Preclinical Innovation and Patient Safety Initiative: Recommendations for Modernizing Preclinical Testing

Presenting Author: Elizabeth Baker

9:15 a.m. – 4:30 p.m. (Author Attended: 10:45 a.m. – 12:15 p.m.)

Convention Center Exhibit Hall

Abstract: Preclinical drug testing is critical to understanding the toxicity, pharmacology, and pharmacokinetics of candidate drugs. The Preclinical Innovation and Patient Safety (PIPS) Initiative fosters collaboration among drug development stakeholders—including federal agencies, patient, research and health organizations, academia, technology companies, and the pharmaceutical industry—to implement modern human-focused preclinical approaches. Participants recognize that more predictive approaches are fundamental to the timelier delivery of safe and effective medicines. This presentation highlights the scientific, regulatory, policy, training and educational recommendations made by a group of stakeholders during the kick-off roundtable in January 2017, and explores three projects identified by PIPS participants as likely to provide high impact on the field of toxicology. First, modern approaches to validation should incorporate human data. This is the only way to overcome the challenge of comparing human in vitro approaches to currently available animal safety data. The legislation 21st Century Cures and the Prescription Drug User Fee Act mandate that FDA make real world human data/evidence more accessible. PIPS identified that implementation of the mandates should include making real world evidence available to method developers for validation purposes in order to better understand a method’s predictive ability. Second, researchers must have access to human cells and high-quality tissues in order to use human-focused approaches. Currently, there are no guidelines for collection and care of human cells and tissues intended to be used for research. PIPS is coordinating efforts to develop guidelines to ensure the increasing demand is met. Third, despite significant private and public investment in the development of human-focused approaches, many FDA regulations require animal data. While industry may use modern approaches for internal decision-making, the regulatory requirements prioritize animal data and dis-incentivize use of modern approaches. PIPS has identified the regulations and coordinated multiple projects to push the agency to update the regulations to reflect flexibility that allows for evolving science. 

Tuesday, March 13

Hands-On Seminar: Creating an Adverse Outcome Pathway in the AOP Wiki

5 – 7 p.m.

Grand Hyatt Rooms Bowie A – B 

The Human Toxicology Project Consortium and the Physicians Committee for Responsible Medicine invite you to deepen your understanding of the AOP Wiki and gain experience entering an Adverse Outcome Pathway in a structured, hands-on seminar Tuesday evening. 

Version 2.2 of the AOP Wiki was released in January 2018.  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. We will also present an available online course on AOPs, and course attendees will work through a case example in small groups

See full agenda and please register in advance to Registration is appreciated, but not required. Please indicate whether you will bring a laptop.

Thursday, March 15

Poster Session:  Late-Breaking 01: Model Systems

Title: Towards an IATA for Chemical Respiratory Sensitization: Establishment of Reference Chemicals to Evaluate In Vitro and In Silico Approaches

Presenting Author: Kristie Sullivan

8:30 – 11:30 a.m.

Convention Center Hall 1

Abstract: Public health and regulatory needs require approaches to detect and discriminate respiratory sensitizers from dermal sensitizers; however no single method or strategy is generally accepted. An Adverse Outcome Pathway (AOP) for respiratory tract sensitization by low molecular weight organic chemicals identifies several promising in vitro methods. Most of these methods have only been assessed with a few well-known respiratory sensitizers (e.g., toluene diisocyanate or trimellitic anhydride). To further evaluate the utility of these in vitro methods, we have set out to build a more comprehensive list of reference chemicals, including known respiratory irritants, non-sensitizers, and dermal sensitizers. The ideal list of respiratory sensitizers should cover a range of chemical classes and include “challenging” chemicals, such as respiratory sensitizers thought to elicit effects through dermal exposure and those for which specific-IgE has not been detected in humans. To build the list, we are conducting a review of established structure-based profilers, recent literature, and human clinical reports, focusing on data verified in humans for translatability to human health outcomes. We are also making use of the Abstract Sifter literature review tool (Baker et al., (2007)) to identify additional potential respiratory sensitizers. Briefly, a set of PubMed MeSH terms describing adverse effects (AEs) for 92 known sensitizers was used to query a large database of chemicals and AEs, yielding over 7000 chemicals of potential interest. The top 500 ranked chemicals (based on article counts) are currently undergoing manual review. This reference chemical list is an important step towards an assessment of potential test methods and creation of internationally-harmonized integrated approaches for the detection of chemical respiratory sensitizers.