As many as 90 percent of new drug compounds fall short in clinical trials. Many of them fail because the compounds are toxic in humans, particularly to the liver and kidneys. Though pharmaceutical companies use cell cultures and animal models to assess toxicity issues before their drugs go to human trials, those approaches have shown mixed success.  

This established preclinical workflow is wasteful on many levels. Drug companies expend precious resources on new drug applications that are doomed to failure. Clinical trial participants are often exposed to toxic compounds, and some have paid dearly. Patients hoping for more effective medicines must continue to wait. 

In an ideal world, pharma companies would fully understand a drug’s potential toxicities long before it goes to human trials. If the compound is found to have toxicity, medicinal chemists could alter the molecule to mitigate the problem. In other cases, resources could be shifted to drugs that have fewer toxic effects. 

To get there, we need to augment the preclinical workflow, leverage new models, and provide better data on drug toxicity with in vitro toxicology testing at the early stages of research and development. Organ-Chips are a promising option. 

The Advantages of Organ-Chips  

Emulate has developed liver and kidney chips that can provide truer readouts on drug toxicity. These small microfluidic chips, about the size of an AA battery, are designed to better replicate the forces and signals cells encounter in vivo

Kidney toxicity is a major reason therapeutic compounds fail in human trials. Toxicity often shows up in the renal proximal tubules, which are responsible for filtering the blood. The Emulate human Proximal Tubule Kidney-Chip was created to model this behavior. The chip contains both tubular and vascular endothelium to replicate mechanical and physiological forces in the body, such as cellular signaling and shear stress, and provide a model that will more accurately predict how these cells respond to medicines or other compounds.  

In addition, because organ-chips are made from a clear polymer, they can be visualized. For example, researchers can easily examine cellular morphology under a microscope.  

Emulate recently tested the Kidney-Chip against cisplatin and gentamycin, which are known nephrotoxic agents. The cells in the chip reacted to these toxins much like cells in the body, showing obvious injuries. In addition, by studying gene expression and other factors, Emulate researchers showed the chips reproduced cellular transporters, which play a significant role in toxicity, and other important kidney mechanisms. Ultimately, the study showed the chip offers a physiologically relevant way to assess drug safety. 

A Dynamic Preclinical Model

Instead of studying compounds on cell cultures, followed by animal models, followed by human participants, researchers can layer in this new model, which more closely replicates how cells behave in the body. Organ-Chips will not replace cell culture or animal models in the immediate future. Rather, they provide a vehicle to inform preclinical data and ultimately predict a drug’s potential toxicity. 

The goal is to catch toxicity much earlier in the process, a refinement that could reduce waste, giving pharma companies better data to decide which compounds move forward into new drug applications and which ones should be reexamined.   

Having this extra layer of data could ultimately make clinical trials more efficient, increasing success rates, reducing the dangers to trial participants and accelerating the drug discovery process. 

On March 10th, 2021 Rep. Alcee L. Hastings (D-Fla.) and Citizens for Alternatives to Animal Research (CAARE) hosted the “21st Century Alternatives to Animals in Biomedical Research” virtual briefing in support of the Humane Research and Testing Act, re-introduced by representatives Hastings and Vern Buchanan (R-Fla.). Attending staffers had the opportunity to hear from a variety of scientific and medical experts and renowned primatologist Jane Goodall about the need to explore alternatives to animal models for biomedical research. Don Ingber, Scientific Founder of Emulate, spoke about how organ-on-a-chip technology can overcome many of the scientific inadequacies and ethical concerns associated with animal models. Together, the speakers highlighted many opportunities to improve drug discovery that will come from creating a National Center for Alternatives to Research and Testing as part of NIH. The message was clear — the use of animal studies and testing is not only inhumane and expensive, but it also doesn’t produce human-relevant data. More compelling human-relevant testing solutions, like Emulate Organ-Chips, are now available.  

Dr. Jane Goodall, founder of the Jane Goodall Institute, began the briefing by recounting one of the “worst days of [her] life:” when she visited a laboratory in the 1980s that used chimpanzees as test subjects. Dr. Goodall stressed that animal testing foundationally violates the rights of animals by subjecting them to a life of captivity and testing that could induce pain and fear in them. “Animal models really aren’t the answer,” she said. 

In addition to their ethical implications, animal studies have proven themselves insufficient in addressing today’s complex public health concerns, according to Paul Locke, JD, DrPH, Associate Professor at the Johns Hopkins Bloomberg School of Public Health and affiliate of the Center for Alternatives to Animals. Locke discussed how more sophisticated testing techniques can better imitate human biological processes and will facilitate the development of novel drugs and therapies with improved accuracy and efficiency. He emphasized that “research has shown us that non-animal methods are definitely the way to go.” 

Emulate Scientific Founder and Board Member Don Ingber presented about the benefits of organ-on-a-chip technology in his capacity as the Director of the Wyss Institute for Biologically Inspired Engineering at Harvard University. He discussed how Organs-on-Chips can be a solution to the demonstrated need for sophisticated, human-focused modeling in biomedical research. He showed attendees animated models of the organ-on-a-chip models and videos of experiment data to demonstrate how organ-on-a-chip technology can replicate and illustrate human biological functions. 

One field that could especially benefit from non-animal research methods is cancer research. “Cancer treatment has remained paleolithic,” noted oncologist Anza Raza, MD, Chan Soon-Shiong Professor of Medicine and Director of the MDS Center at Columbia University and author of the book The First Cell: And the Human Costs of Pursuing Cancer to the Last. Dr. Raza described how cancer treatment has seen little change in approach since the 1970s with the rudimentary tools of surgery, chemotherapy and radiation. Expressing disgust for new cancer therapies which only work for a subset of patients and often only for a short time, she noted “95 percent of experimental drugs fail, and the other 5 percent should have failed.” Anza views inapplicable animal models as a primary reason for cancer treatment’s stunted progress. She stressed that human-oriented models need to be used to understand cancer and other human diseases.  

Finally, Thomas Hartung, MD, PhD, Professor at the Johns Hopkins Bloomberg School of Public Health and Director of the Center for Alternatives to Animals, closed the briefing by stating the importance of the NIH’s role in normalizing new research techniques, and funding research to spur their development and use. He also described the importance of training the next generation of biomedical researchers on the most effective and cutting-edge tools and research methods, which he saw as necessary to making animal models a thing of the past.   Please visit to find your Congressional representative and encourage him or her to support the Humane Research and Testing Act.

In developing new medicines, the pharmaceutical industry has relied on antiquated research paradigms, established in a different era when the collective human understanding of animal biology was very different. The limitations of animal models in research were somewhat known, but at the time, they were the best available tools for predicting drug safety and response before human trials. In the intervening years, research conducted, and data revealed have given us reason to question the status quo.   

Today, more human-relevant models, such as new organ-on-a-chip technologies, exist which can help researchers understand mechanisms of disease and drug action. Newer pharmaceutical advances which harness the human immune system, or human-specific biological factors, represent roughly 40 percent of the pharmaceutical pipeline.  Animal models simply don’t work in predicting human responses to many biologic medicines and vaccines, and they present a myriad of ethical concerns and geopolitical challenges.  

To improve drug discovery, a paradigm shift is needed. Governments need to invest in future-focused solutions and create pathways for regulators to approve safe and effective drugs based on a wider variety of human-relevant modeling methods. At Emulate, we believe that the Humane Research and Testing Act (HR 1744), recently introduced, is the first step toward that paradigm shift the pharmaceutical industry so desperately needs, and we are proud to give it our endorsement.  

The bipartisan legislation introduced into the U.S. House of Representatives by Rep. Alcee Hastings (D-Fla.) and Rep. Vern Buchanan (R-Fla.) would establish the National Center for Alternatives to Research and Testing under the National Institutes of Health. The new Center would be dedicated to increasing transparency and understanding regarding the use of animals in research and testing and would be focused on ultimately reducing the number of animals used in such practices. It would require the NIH to develop, fund and execute a plan to enumerate the number of animals used in biomedical research, and incentivize companies to use non-animal methods by educating and training scientists on human-relevant research methods.  

Emulate is proud to endorse this legislation as we believe it is an essential first step toward ensuring that human-relevant models play a larger role in biomedical research.  We applaud Rep. Hastings and Rep. Buchanan for their leadership on this issue, as well as Representatives Joyce Beatty (D-Ohio), Julia Brownley (D-Calif.), and Lucille Roybal-Allard (D-Calif.) who are original co-sponsors of the bill.