The Physicians Committee

Good Science

November 2017

November 27, 2017   animal testing, cancer


Mice are telling cancer researchers to give it up

It is widely known that mouse research to study human cancers is fraught with unreliability. Scientists have for decades attempted to replicate human cancer growth and treatment responses in mice by disabling their immune systems and grafting human-cell-line-based cancers onto them, a model known as a xenograft. These studies have notoriously faulty outcomes. A new report has shown that recent “improvements” to this technique are just as faulty.

In general, cancer animal research (see here, here, and here) has a failure rate of at least 95 percent, as determined by the results of clinical trials based partly on mouse studies. The few "successes" are usually clinically irrelevant, providing minimal or no real-life value. A 2014 study from the National Cancer Institute revealed an average 2.1 month life prolongation (and often as little as a few days) for the 72 cancer drugs approved from 2002-2014, and even this minimal benefit is illusory in two-thirds of the drugs in clinical use.

Researchers characteristically address the very high attrition rate for drugs developed from animal research by postulating that “better” techniques with animals are needed. Various approaches to improve the predictability of these stand-ins for human cancers have been tried without success. In recent years, there has been much hope ascribed to an approach referred to as patient-derived xenografts (here, here, and here). The mice used in these studies are termed PDX mice and are often called human avatars. To produce these avatars, extracts from human cancers (obtained by biopsies or surgical excisions) are injected into mice, thereby creating mice purportedly expressing the injected cancer. These models can be created from a patient's own tumor, in which case the patient then has a “model” specific for his or her own cancer. It has been thought that such "precision oncology" models will remedy the problems with cell-line-derived cancer tissue, and will identify tumor markers, genetic targets, and effective treatments for a patient's specific cancer.

A recent report from Boston researchers reveals why the ballyhooed PDX approach fails to solve the age-old problem of translation from mice to humans—a problem researchers understandably call the Valley of Death. Using 1,110 tissue samples from 24 different cancer types, these researchers evaluated genetic changes occurring after transplantation of patient-derived cancer tissue into PDX mouse avatars.

Genetic changes in the transplanted tumors occurred rapidly, and these were markedly different from initial genetic characteristics and genetic changes observed during tumor evolution in patients. Genetic mutations noted in patient tumors sometimes disappeared after transplantation. The authors concluded: "Notably, the genomic stability of PDXs was associated with their response to chemotherapy and targeted drugs. These findings have major implications for PDX-based modeling of human cancer."

In other words, the human cancer in the PDX mouse's biological environment leads to mouse-specific changes that invalidate the mouse as a descriptor of the human tumor or as a method for identifying tumor targets and developing treatments. It is no wonder that this precision oncology approach displays no more precision than previous failed cancer research methods using mice. Similar genetic discrepancies would surely be expected for any species using PDX technology, and the conclusion remains that nonhuman research is immutably inadequate for the study and treatment of human cancers.

Where to from here? First, it's long past time that we take notice of the many ways that mice have shown us that they are not tiny humans. Despite decades of research model manipulation, mice are no better at recapitulating the course or treatment responses of human cancers. Second, the logical transition to human-relevant cancer research methods is overdue. Whether the barriers to this transition are researcher arrogance, career and funding considerations, or regulatory restrictions, these must be overcome if the abject failure of mouse research for cancer is to be reversed.

November 13, 2017   other


Physicians Committee Medical research program director Ann Lam, PhD, with award winners Dr. Francesca Pistollato and Dr. Lena Smirnova, and Green Neuroscience Laboratory director Elan Ohayon, PhD.

Physicians Committee Medical research program director Ann Lam, PhD, with award winners Dr. Francesca Pistollato and Dr. Lena Smirnova, and Green Neuroscience Laboratory director Elan Ohayon, PhD. 

For the second year in a row, the Physicians Committee is partnering with the Green Neuroscience Laboratory to present the Green and Open Neuroscience Hero Awards for outstanding contributions to human-relevant research. This round of awards will be given at the 3rd Annual Green and Open Neuroscience Symposium & Soiree Nov. 13, 2017 in Washington, D.C. The free and public event is held as a satellite to the annual Society for Neuroscience meeting, the world’s largest annual meeting of neuroscientists, and will inform scientists about the promise of neuroscience research conducted without animals.

This year, two awardees are being recognized for their contributions. Awardee Dr. Lena Smirnova, research associate at Johns Hopkins University Bloomberg School of Public Health and the Center for Alternatives to Animal Testing, works to develop human “mini-brain” 3-dimensional organoids and other cell models to study the impact of environmental chemicals on brain function. The second recipient, Dr. Francesca Pistollato, research scientist at the European Commission Joint Research Center, is acknowledged for her work on human-based science, particularly with human induced Pluripotent Stem Cells (iPSCs) in the area of Alzheimer’s disease.

The Green and Open Neuroscience Hero Award is given to scientists, educators, policymakers, or advocates who help improve our understanding of the brain and health through research and perspectives that strengthen ethics, open science, the environment, education, arts and protection of neurodiversity (See also: These heroes exemplify how science can be dramatically advanced while maintaining the highest standards of responsible science.

Through presentations, discussions, and music, the evening soiree is both a celebration and an opportunity to consider potential collaborations and the necessary steps that need to be taken in neuroscience in order to promote groundbreaking, humane research in the 21st century.

Last year’s winners include Dr. Jacopo Annese of the Brain Observatory, for his work to create a high-resolution human brain atlas to humanize the understanding of the brain, and Dr. Stacey Lopresti-Goodman of Marymount University, for her groundbreaking research on animal cognition and outstanding contributions to forwarding ethical science education.

The event is open to the public, with an optional registration here.

November 11, 2017   animal testing


Awardees are given a hand-made hare statue to signify the prize's emphasis on "fighting animal testing". Pictured are Kristie Sullivan, MPH, Physicians Committee's vice president for research policy, Sara Amundsen, Humane Society Legislative Fund, and Catherine Willett, PhD, Humane Society of the United States.

We are excited to announce that, together with our partners, the Physicians Committee has won the Lush Lobbying Prize, which is awarded each year to organizations or individuals “pushing for change, focusing on policy interventions promoting the use of alternatives.” This award acknowledges our work with the Humane Society of the United States and the Humane Society Legislative Fund on the Frank R. Lautenberg Chemical Safety Act for the 21st Century. This bill, which was enacted into law in June 2016, contains the first ever national United States requirement for the Environmental Protection Agency (EPA) and chemical companies to consider and use alternatives to animals in chemical testing. The EPA is also required to create a strategic plan to replace and reduce animal tests, provide incentives to use non-animal alternatives, and report regularly to Congress on its progress.

Eighteen winners from all over the world are being honored for their contributions to end animal testing in science, public awareness, training, and lobbying at an awards gala in London, the evening of Friday, Nov. 10. The lobbying award prize totals 50,000 British pounds and will be shared among the three organizations.

The Lautenberg Act signals a new direction in chemical assessment, in which human-relevant test methods and approaches are required to be used, developed, and promoted by the EPA and any entities providing chemical toxicity data to the EPA. By requiring the EPA to replace and reduce the use of animals in chemical testing, create a strategic plan to implement nonanimal methods into their chemical assessment practices, and report to congress on its progress every five years, it represents the beginning of the end of animals killed in toxicity testing.

Kristie Sullivan speaks at Friday's awards ceremony in London.

Thank you to the Lush Prize for recognizing this achievement.

November 8, 2017   animal testing


Physicians Committee Scientists Provide Expert Advice on Replacing Animal Tests

“Proper planning prevents poor performance.” It’s a timeless quote used to inspire people to apply adequate thought prior to any action in which great results are expected. U.S. governmental agencies are making plans to move away from animal testing to what many are now calling “new approach methodologies”—a catch-all term referring to nonanimal toxicity test methods. Physicians Committee toxicologists Esther Haugabrooks, Ph.D., and Kristie Sullivan, M.P.H., capitalized on the opportunity to aid in the proper development of this plan by providing advice to regulators and other government scientists at the Scientific Advisory Committee for Alternative Toxicological Methods (SACATM)’s annual meeting.

SACATM is a federally chartered advisory committee for the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), and the Directors of the National Institute of Environmental Health Sciences (NIEHS) and NTP. This committee and its advisee agencies are the hub of government efforts to replace animals in toxicology.

The U.S. government has finally begun to put serious resources toward replacing animals in chemical, pharmaceutical, and other product testing. To properly plan these investments, NICEATM is creating a U.S. Strategic Roadmap: New Approaches to Evaluate the Safety of Chemicals and Medical Products, which ICCVAM has been developing since earlier this year. The roadmap is centered on three main goals:

  1. Encourage the adoption and use of new nonanimal methods and approaches by federal agencies and regulated industries;
  2. Foster the use of efficient, flexible, and robust practices to establish confidence in these new methods; and
  3. Connect end-users with the developers of nonanimal methodologies.

Other updates shared at the meeting and further indication of the resources available to reduce the use of animals in safety testing include EPA’s progress in using high-throughput nonanimal methods to quickly screen a large number of chemicals for safety and its very own strategic plan on replacing animal tests under the Lautenberg Chemical Safety Act.

Physicians Committee toxicologists gave several technical comments during the meeting. We commended the work of NICETAM in leading U.S. agencies towards the common goal of replacing animals, and for the ambitious, specific plans outlined to achieve this goal.

We encouraged ICCVAM member agencies, such as the Food and Drug Administration, to be more aggressive in implementing and requiring industry to use such technologies especially for the cases where nonanimal alternatives are already available.

And we suggested in order to make faster progress, the United States needs to share its technological developments with agencies in other countries, and that chemical and pharmaceutical companies should do its part to share data and fund validation of nonanimal methods. Furthermore, the Physicians Committee and other organizations are providing opportunities for training that regulators can leverage to continue to increase the use and acceptance of nonanimal methods.

Kristie Sullivan, M.P.H.
Kristie Sullivan, M.P.H., Physicians Committee toxicologist and vice president of research policy, providing comments at SACATM.

For more information on the SACATM meeting, click here.

Later that week, the American Society for Cellular and Computational Toxicology (ASCCT), a scientific society co-founded by the Physicians Committee, held its 6th annual meeting in the Washington, D.C., metro area. ASCCT is a rapidly growing society that supports toxicologists working to develop nonanimal toxicology approaches by 1) providing opportunities to communicate and collaborate with each other and with regulatory authorities, 2) facilitating mentorship and training opportunities for young toxicologists, and 3) highlighting new toxicology approaches that do not use animals.

ASCCT organizers took advantage of the themes presented at the SACATM meeting to delve deeper into the science and policy behind the progress reported by government agencies. During the two-day ASCCT meeting attendees could view posters and attend session with presentations from EPA regulators and leading scientists from industry and nonprofit organizations.

The first day, tandem presentations by Anna Lowit of the EPA and Dan Wilson of Dow Chemical Company focused on stakeholder efforts to replace the EPA six-pack—a battery of animal intensive tests to determine acute systemic toxicity for (1) oral, (2) dermal, (3) inhalation routes of exposure, (4) skin corrosion and irritation, (5) eye corrosion and irritation, and (6) skin sensitization—with alternative approaches. Several shorter presentations highlighted the exciting scientific work making it possible to replace these tests.

The second day focused on the EPA’s responsibility to reduce and replace animals under the Lautenberg Act, with presentations and a panel discussion, moderated by the Physicians Committee’s Kristie Sullivan, again focusing on the scientific and policy needs to achieve this objective.

The Physicians Committee gave two poster presentations and one oral presentation. Elizabeth Baker, Esq., senior policy specialist, presented her work on Preclinical Innovation and Patient Safety: A Collaborative Approach to Supporting Innovative Science and Replacing Preclinical Animal Tests  and Esther Haugabrooks, Ph.D., presented a survey of global testing requirements titled Understanding Global Acute System Toxicity Testing Requirements as a Framework for Rapid and Harmonized Acceptance of Alternative Approaches .  Dr. Haugabrooks also presented an oral presentation outlining recommendations for the EPA strategic plan.

Dr. Haugabrooks, Physicians Committee toxicologist Esther Haugabrooks, Ph.D., Physicians Committee toxicologist, giving a presentation entitled the ‘Vision for U.S. Strategic Plan to Implement Alternative Toxicology Testing’ at the ASCCT meeting.

Baker by her poster at ASCCT.

Elizabeth Baker, Esq., senior policy specialist, by her poster at ASCCT.

For a full list of the ASCCT presentations, click here.

It is evident from the scientific presentations and discussions at the ASCCT meeting that the science of new approach methodologies has surpassed the archaic use of animals to predict human safety, and that we are already seeing the legislative mandates in the Lautenberg Act inspiring more scientific progress.

Proper preparation through scientific advances will make it possible to shift from traditional toxicology testing to alternative, nonanimal methods. Some of these methods, as highlighted at SACATM and ASCCT, are already being used within U.S. regulatory agencies. However, with the development of ICCVAM’s strategic roadmap, the EPA’s strategic plan to promote and develop alternative methods, and the continual efforts nongovernmental organizations like the Physicians Committee, a broader acceptance of nonanimal approaches within regulatory agencies is on the rise.

The Physicians Committee is looking for two spring semester interns to work on our programs promoting the replacement of animals in testing, research, and medical education with human-relevant methods. Apply today!