The Physicians Committee

Good Science

February 2018


testing road map

Image Credit: FDA.

A growing number of scientists are realizing that biological and physiological differences between—and even among—species are leading to failures in the development of safe and effective medicines.

Scientists from a variety of backgrounds are working to develop better methods to evaluate safety. And they have been successful in elevating our abilities to investigate how investigational new medicines interact with human cells, tissues, and biological and physiological processes.

As is often the case, law and policy did not keep pace with science. Now, we are at a standstill, where many of these so called “human-based” scientific approaches already exist for evaluating medicinal safety, such as organ chips and computational methods, but they have not been fully utilized for multiple reasons.

One main hindrance is Food and Drug Administration (FDA) regulations.

Before the regulated industry can be expected to implement a new approach to answering a regulatory question for the FDA, industry must be confident that the FDA will accept the new approach.

One step towards implementation is regulators clearly communicating that human-based approaches, such as advanced in vitro and in silico approaches, are accepted if sufficiently evaluated. FDA may start this communication by broadening the regulations that currently require animal data.

FDA staff have stated informally at meetings, that the agency retains discretion to accept modern approaches to assessing safety that do not use animals. Certainly, the law of the land allows it.

The Federal Food, Drug, and Cosmetic Act (FFDCA) is the United States law that gives FDA the authority to regulate drugs. The FFDCA does not mandate animal data for pharmaceutical development. Rather, this mandate arises from FDA promulgated regulations.

In September 2017, an FDA blog announced that a Regulatory Reform Task Force would review agency regulations and requested input on regulations that need to be modified or repealed because they place an burden on the regulated community. This was the opportunity we needed, as we had already been recommending that FDA broaden regulations that currently require animal data to also allow for the use of modern approaches that are based in human biology and physiology.

We combed through the Code of Federal Regulations and ultimately identified 235 regulations that should be changed because they place a burden on industry to use animals, even if a more predictive or cost-effective approach is available.

Our suggestions should be adopted because they remove this burden, help ensure the longevity of the regulation in the face of rapidly advancing science, and will help FDA improve product safety and meet its goal of replacing and reducing animal testing.

Making the proposed regulation changes would be consistent with FDA’s own participation in the National Institutes of Health (NIH) and Defense Advanced Research Projects Agency (DARPA) tissue chip collaborations and the vision for advancing the methods available to drug sponsors through FDA’s own Predictive Toxicology Roadmap.

Bookmark our Good Science Digest to stay updated on how the Regulatory Reform Task Force and FDA responds to our input.

We are seeking a student or recent graduate interested in promoting alternatives to the use of animals in medical research and education for our summer 2018 Replacing Animals in Research Internship. Apply today!

February 23, 2018   animals in education


In February 2018, science fiction became science fact, as scientists in Shanghai reported the successful cloning of cynomolgus monkeys (long-tailed macaques) using a process called somatic cell nuclear transfer (SCNT). This is the same process used in 1996 to clone Dolly the sheep, and it was subsequently used to produce live births in more than 20 other species.

But SCNT uniformly failed in primates until the Shanghai group discovered how to promote the growth of the created embryo in a surrogate mother macaque. Although nearly all the implanted embryos did not survive, two live births resulted—genetically identical sisters Zhong Zhong and Hua Hua.

SCNT operates by obtaining a donor oocyte (egg cell), then removing the nucleus and inserting a cultured fetal fibroblast (connective tissue cell) from an aborted fetus. Techniques developed by the Shanghai researchers promote the development of the created embryo after transfer to a surrogate mother (Figure).

Cloning of macaque monkeys by  somatic cell nuclear transfer.

Source: Liu, et al. Cloning of macaque monkeys by somatic cell nuclear transfer. Cell 2018;172:1-7

The purpose of this research is to create populations of genetically identical monkeys to facilitate research into human diseases, and particularly neurological disorders such as dementia and Parkinson disease that have escaped elucidation and treatments based on animal research. The presumption is that by eliminating genetic variation as a complicating factor, fewer monkeys can be used while obtaining more reliable information from (for example) monkey brain research.

Concerns and objections to this research are based on the claimed usefulness of the cloned monkeys for human-relevant science and on several ethical issues, raised even by the researchers themselves. The cloning of genetically identical monkeys does not address the fundamental reasons that nonhuman animal research is unreliable for human applications. These reasons include extensive and immutable genetic differences between humans and nonhuman primates (here, here, and here), including very different brain genetics (here, here, and here).

Since human monozygotic (identical) twins differ in gene expression, disease risks, and responses to treatments (here and here), even for brain disorders, claims that the cloned monkeys can translate to human benefit are unscientific.

Regarding the ethical concerns, where do we start? The SCNT process begins by aborting a fetus from a mother impregnated for that purpose. Another monkey has an egg cell removed from her ovary. Then after the egg cell and fetal fibroblast are fused to create the embryo, it is transplanted into a third monkey (the surrogate mother). If the embryo produces a live birth, the newborn is taken from the mother and maintained in a captive environment, only to be used and killed in cruel and futile experiments.

Finally, this achievement by Chinese scientists moves us one huge step closer to the possibility of cloning humans, a process these researchers state they will not pursue. But there is a reliable dogma in medical science: If it can be done, someone will do it. Only legislation and science ethics prevent this, and does anyone want to rely on those shaky deterrents? 

Legendary World War II general Omar Bradley stated regarding the advent of the atomic bomb: "The world has achieved brilliance without wisdom, power without conscience." As China awaits the birth of as many as six more cloned monkeys, here we are again.

We are seeking a student or recent graduate interested in promoting alternatives to the use of animals in medical research and education for our summer 2018 Replacing Animals in Research Internship. Apply today!

February 22, 2018   animal testing, animals in education


Five Top Challenges for Animals in 2018

1. Animals Are Killed in Military and Medical Training

For years, the Physicians Committee and others have been pushing the Department of Defense to stop using goats and pigs to train medics and corpsmen (the Navy’s equivalent to medics). In these courses, animals are shot with firearms, stabbed, and dismembered. But jaw-droppingly realistic devices are available that replicate human anatomy, and some parts of the military are getting the message that these devices are better than nonhuman animals. We have already started the year strong, bringing to light the unauthorized use of animals by the Marine Corps and highlighting efforts within that branch of the military to replace animals. We also partnered with former M*A*S*H actors Jamie Farr and Mike Farrell and placed three billboards in San Antonio, Texas, to bring this issue to the attention of the Army Surgeon General. We have plenty more planned in the months ahead.

2. FDA Regulations Still Mandate Animal Testing

While we have succeeded in changing law and policy in the chemical sector, and now U.S. law states the Environmental Protection Agency (EPA) and the chemical industry must use and develop alternatives to animal testing, the Food and Drug Administration (FDA) lags behind. Current FDA regulations were established decades ago and do not provide flexibility to support modern science. Many regulations mandate that animal tests must be conducted prior to clinical trials in humans. However, drug development stakeholders—including the FDA itself, other federal agencies and private industry—now acknowledge that animal tests fail to predict human outcomes 95 percent of the time. Through the Preclinical Innovation and Patient Safety (PIPS) initiative, we have recommended the FDA update the regulations to allow for use of any scientifically evaluated preclinical approach, whether or not it involves animals. As part of regulatory reform at FDA, we combed through agency-wide regulations to identify specific regulations that need to be changed and provided proposed language and justification. We will continue to provide input to FDA on this issue and push for updated regulations. We are hopeful that 2018 is the year of regulation change, as our recommended changes complement roadmaps recently unveiled by the FDA and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) that aim to improve testing by moving away from animal tests.

3. Animal Research Interests Seek to Decrease Protections for Animals in Labs

A troubling new effort led by organizations that represent animal experimenters and their institutions aims to drastically cut protections for animals in laboratories. Essentially, they would like to create an oversight system that allows laboratories to self-regulate—when federal laws and government enforcement are already extremely lax. One of their recommendations is to drastically reduce how often most research facilities are inspected by the U.S. Department of Agriculture (USDA), which would significantly impair the public’s ability to monitor those facilities’ compliance with the law. In addition, USDA is proposing recognizing third-party inspections of research facilities, which would ask animal experimenters to help monitor themselves. The Physicians Committee is working with a large coalition of organizations to lobby Congress, the USDA, and the National Institutes of Health (NIH) to maintain or even strengthen current laws and regulations—not weaken them. In the months ahead, we'll be asking our supporters to contact these agencies and likely their members of Congress.

4. Government Budget Jeopardizes Funding For Human-Based Research

Last year, the Administration proposed major budget cuts for the EPA - nearly half of current levels. EPA funding cuts put the future of human-based research at stake because a lack of funds would inhibit EPA's ability to continue developing modern safety assessment methods that do not use animals. We lobbied to maintain the research budget for alternatives – and won! But the work continues. The Trump Administration’s recently-released budget cuts this funding from EPA again. The National Institutes of Health (NIH) has begun funding some really excellent human-focused research such as the National Center for Advancing Translational Sciences (NCATS) and small business grants to companies developing alternatives. However, the research funds directed towards human-based testing are a drop in the bucket compared to research dollars invested in animal testing. In order to quickly and responsibly develop and integrate modern, predictive testing approaches, we must call on our government to increase funding of research that can be expected to be more predictive for humans because it is based on human cells, tissues and biological processes.

5. High-Quality Human Cells and Tissues For Research Are Not Easy To Obtain

While many people understand the reasons for human-based research, using human cells and tissues, fewer people understand how these tissues are obtained for research. One way human cells and tissues are obtained are as byproducts of surgery.  Many of us have the option to donate tissue to research that would otherwise be discarded. However, this option is not always presented to patients. We must increase the availability of human cells and tissues used for research, by educating the public and beginning a discussion on best practices for tissue procurement. We will bring together stakeholders to surmount some of these practical problems.

We are seeking a student or recent graduate interested in promoting alternatives to the use of animals in medical research and education for our summer 2018 Replacing Animals in Research Internship. Apply today!