There is an emerging biotech movement that promises to transform medical science and radically overhaul the arduous process of bringing new drugs, foods and cosmetics to market.
Teams of academic and government researchers and a handful of start-ups have created human organs-on-chips — miniaturized versions of livers, lungs, kidneys, intestines and other vital innards. The nascent science, now being evaluated by the FDA, offers a less time-consuming and costly way to test drugs, foods, cosmetics and dietary supplements for efficacy and toxicity, with the goal of vastly improving upon traditional cell culture and animal-based methods.
It sounds futuristic, but it's not sci-fi. Each organ-on-a-chip, roughly the size of a AA battery, is made from a flexible, translucent polymer. Inside are tiny tubes, each less than a millimeter in diameter, lined with living human cells extracted from a particular organ. When nutrients, air, blood and test compounds, such as experimental drugs or cosmetic ingredients, are pumped through the tubes, the cells replicate some of the key functions of that organ, just as they do in the body.
Data published by FDAReview.org, a project of the nonpartisan Independent Institute, indicates that only about 1 in 10 drugs that enter clinical trials ultimately win Food and Drug Administration approval. According to the California Biomedical Research Association, it takes an average of 12 years for a drug to travel from preclinical research to the patient, at an average cost of $359 million. Do the math on the 90 percent of those drugs that don't make it and you can see the need for a revolutionary new approach.
"The current tools don't always give us the complete picture," said Geraldine Hamilton, president and chief scientific officer at Boston-based Emulate, a three-year-old private spin-off of the Wyss Institute for Biologically Inspired Engineering at Harvard University, a pioneer of organs-on-chips that has a multiyear R&D agreement with the FDA.
"When you put cells in a [petri] dish, they're in a static environment and don't interact with each other in the same way as they do in the body," she said, referring to a common preclinical first step. Tests on animal systems, Hamilton added, often do not accurately translate to those in humans, because of dissimilarities in our respective biologies.
Emulate has combined design, engineering and biology to recreate a dynamic microenvironment housed within its organ chips. "Think of the chip like a home away from home for an organ," Hamilton explained. "We can control the way cells interact with each other by applying relevant mechanical forces." For example, Emulate's lung chip can simulate breathing in and out. Blood and airflow are reproduced in the chip's tiny channels.
Besides increasing the speed and accuracy of drug testing, organs-on-chips present a range of game-changing potentials. They can be embedded with a particular disease, such as cancer or asthma, and provide researchers with a cost-effective mini laboratory for introducing immune cells or drugs and observing reactions in real time. It's also possible to grow separate chips of a human gut, a cow gut and an insect gut and then compare how each species' intestines react to a pesticide, an implausible experiment using those actual animals. Further down the road are you-on-a-chip models containing stem cells, a key component in so-called personalized medicine, and an entire human-on-a-chip, linking every organ together to study holistic interactions between cells and tissues.
Although Emulate is the first commercial organs-on-chips venture, this audacious biotech dates back to the late 1990s, when Michael Shuler, a professor at Cornell University's Department of Biomedical Engineering, coined the term "animal-on-a-chip" as part of his research to define the multidisciplinary field, which spans nano science, computational modeling, biomedical engineering, physiology, cell biology and surface chemistry. Shuler is now also president and CEO of Hesperos, an organ-chip start-up in Orlando, Florida. The company has developed separate cardiac and muscle chip systems and is partnering with clients to customize multi-organ chips.
In 2010, Harvard's Wyss Institute, led by Donald Ingber, produced the first successful chip, a lung model. Two years later Ingber's lab was included in a public-private collaboration tasked with creating 10 different human organs-on-chips. The five-year program was backed by a $37 million grant from the federal Defense Advanced Research Projects Agency (DARPA), the National Institutes of Health and the FDA.
In July 2014 and still at Harvard, Ingber founded Emulate, which raised $12 million in Series A funding from private investors. Last year Hamilton and 17 others left their Ivy League confines and set up shop in downtown Boston. The company has since raised an additional $45 million in a Series B round. NIH kicked in a $2 million grant this year, bringing Emulate's total funding to $57 million.
Along with a lung chip, the company has developed liver and intestine models, Hamilton reported, and is working on the next generation, including brain, kidney and skin chips. Emulate is also creating a Human Emulation System, incorporating organ chips, testing instrumentation and software to collect and analyze data. "That will allow this technology to be democratized," she said, "so it can be used by researchers across industries — pharma, food, chemical, cosmetics — government agencies and academia. This is a lab-ready system that enables automation of our product platform."
Emulate plans to make the Human Emulation System available this year but in the meantime is actively partnering with several entities to further develop the basic technology platform capabilities and applications. They're working with Johnson & Johnson on a thrombosis chip to use in developing and testing drugs to treat or prevent blood clots that cause many life-threatening diseases, the Michael J. Fox Foundation to study safety of drugs for the treatment of Parkinson's Disease and with Merck to model asthma and viral infection in the lung.
"We initially focused on the lung-on-a-chip platform," said Stephen Alves, director of Merck's immunology discovery group, "to better evaluate the communication between the various cell types and disease processes of asthma and COPD [chronic obstructive pulmonary disease]. We then expanded that to include the gut-on-a-chip to evaluate gastrointestinal diseases, such as inflammatory bowel disease."
The research is still in the exploratory mode, Alves noted, "but we have demonstrated that you can pharmacologically manipulate aspects of disease. We hope we can move from the organ to a disease model on a chip."
Among Emulate's competitors is TissUse, a German spinoff of an organs-on-chips research program at the Technical University of Berlin's Institute of Biotechnology. Unlike Emulate's single organ chips, though, TissUse is producing ones with two or four organs on each. "We focus on how to combine different organ models so they are able to interact with each other in a systemic manner," said Reyk Horland, vice president of business development at the company, which is jointly funded by the German Ministry for Education and Research and private investors.
TissUse currently has custom-designed products on the market for preclinical R&D, with customers free to choose which organs to put on chips. "We want to have the first fully functional human-on-a-chip prototype combining more than 10 organ models available next year," Horland disclosed.
While this technology is extremely promising, using organ chips in human clinical trials is still a decade or so away. Ironically, a breakthrough that should accelerate the drug-approval process is subject to the rigorous regulatory system.
In fact, even before the FDA considers okaying organ chips for clinical trials on new drugs, the agency recently signed a multiyear R&D agreement with Emulate to validate its organs-on-chips technology for possible use in testing ingredients in food, cosmetics and dietary supplements. The project will begin with a liver chip.
"The liver is particularly susceptible to organ toxicity, as it is the site of toxin filtration and metabolic breakdown, so we thought that the liver chip would be an appropriate place to start," said Robert Sprando, director of the Division of Toxicology in the Office of Applied Research and Safety Assessment at FDA's Center for Food Safety and Applied Nutrition, referring to liver damage.
The first step, however, is to verify the technology behind organ chips, he said. "Initially, we have to do an evaluation of the technology, because one of the questions is, how can this be used in a regulatory environment?" Different from academic research, regulatory research has to address public health standards.
The FDA's meticulous approach to organs-on-chips is emblematic of the way science moves forward from the laboratory to the marketplace — and how this new technology might quicken the pace.
Indeed, Sprando's colleague, senior advisor for toxicology Suzanne Fitzpatrick, summed it up in her FDA blog post written the day the agreement with Emulate was announced: "In some ways, science is like a recipe, in that both can go through a number of incarnations before they work. There's a lot of experimenting and tweaking, collaborating and comparing. And that's what we'll be doing at FDA with the organs-on-chips research. We're excited to be at the forefront of this groundbreaking research, which may one day be routinely used to safeguard public health."
— By Bob Woods, special to CNBC.com