An Interview with Dr. Jesse Goodman of the Food and Drug Administration (FDA)
August 27, 2012
Dr. Pam Osenkowski, Director of Science Programs
While much information can be learned from traditional 2 dimensional (2D) cell culture studies in which cells are grown in a single flat layer, one criticism of 2D cultures is that they are too simplistic, because they do not reproduce the architecture and the anatomy and physiology of tissues in the body. In vivo, cells communicate with one another and with their surrounding environment, and they respond to mechanical cues. These are parameters that are missed in 2D cultures, but scientists are finding ways to recreate some of the complexity seen in vivo. Over the past few years, there has been a lot of hype about the development of microchips with human cells that are constructed to behave like mini-human organs. Two years ago, scientists had already developed the lung-on-a-chip, and since that time, have been able to recreate other mini-organs, including the gut and even a beating heart-on-a-chip. But recently, there has been a lot of excitement over what is called the “Human-on-a-Chip,” a device which would essentially link together ten different mini-organs and the instrumentation that would help analyze data obtained from this model. When completed, this model will have the potential to revolutionize the drug development process, speeding up the time it takes to screen the safety and effectiveness of therapeutics at less cost than current models – and it has the added benefit of being more human-relevant.
The Defense Advanced Research Projects Agency (DARPA), National Institutes of Health (NIH) and the Food and Drug Administration (FDA) have recently joined forces to collaborate on the “Human-on-a-Chip.” This week, I had an opportunity to speak with Dr. Jesse Goodman, FDA’s Chief Scientist, about this innovative technology. The FDA is particularly interested in the development of models that can predict if drugs are safe and effective for the public. As you know, before medicines are used in humans, they undergo extensive testing, some of which involves tests in animals. Although animal models are currently used in many of the toxicity tests that are performed on new drugs, there are scientific concerns about the ability of these models to accurately predict what will happen in people, in addition to animal tests being expensive and time consuming.
It is thought that the “Human-on-a-Chip” may be more likely to mimic the activities and biological processes of the human body because it is constructed from specific human cells types that represent the biology of specific organs and tissues. And because the mini-organs will be linked together, researchers will be able to determine how the metabolism of a drug by one organ will affect other organs.
Dr. Goodman mentioned that FDA scientists are providing input to researchers at academic institutions like the Wyss Institute in Massachusetts to work out the logistics of constructing the “Human-on-a-Chip” and coupling these organ systems together. One of the scientists at the Wyss Institute who has been working extensively on this project is Dr. Don Ingber, Director of the Wyss Institute for Biological Inspired Engineering. Dr. Ingber believes that the “Human-on-a-Chip” may one day replace animal testing and may provide a solution to the problems pharmaceutical companies face with animal models. He was recently quoted as saying, “… there's a real major problem right now in the pharmaceutical industry, which is that the animal models really don't work. We know it's an ethical issue and that many animal lives are lost. And they, you know, they work to some degree, but there's still many, many cases, a surprisingly large number of cases where, you know, millions of dollars, hundreds of millions of dollars and years of development have gone through validating in animal models, and then it gets into the clinic and fails.”
Dr. Goodman stressed that the FDA has a responsibility to ensure that drugs are safe and effective for the general public and sees the “Human-on-a-Chip” as a promising area of research and part of a broad effort to predict the safety and efficacy of drugs. He said that “new science provides an opportunity to improve on what is already being done” and is “totally convinced that [systems with human cells] is the direction to go.” Dr. Goodman also noted that additional potential advantages of human cell systems include the ability to make chips using cells with different human genetic backgrounds, to represent people who may respond differently due to their genetic differences. Also, models of disease states can be created with human cell systems, both to study drug actions and because toxicity may differ from what is seen in healthy states.
Although much progress has been made in the development of the organs-on-a-chip, there is still much work that needs to be done to get the "Human-on-a-Chip" up and running. In addition to working out the technical problems that are inherent with building a complex in vitro system, scientists will also need to have confidence in the results produced by this model. One thing that scientists are curious to discover is whether the “Human-on-a-Chip” will be able to accurately predict toxicity of compounds. Will it be able to identify known toxins as actual toxins? Will it be able to predict toxicity where it wasn’t predicted in animal models? Will there be more or less false positives in this assay compared to others – drugs that appear to be toxic but actually are not? Only time will tell.
The hope is that such microsystems, developed with human cells, will make the process of drug development and toxicology testing faster, more reproducible, more accurate, and importantly, more human relevant – and as an added bonus, help reduce and replace the use of animal tests which, as noted, may not always be fully predictive of findings in humans. Such improvements in testing could also ultimately reduce costs, not only of the testing itself but also, if accuracy is enhanced, through avoiding false positive or negative findings which are often time consuming and costly to drug development. It is wonderful to see progress being made in this very promising field, and I look forward to hearing more about this technology in the future.
I would like to thank Dr. Goodman of the FDA for taking the time to speak with me about this innovative technology, and was pleased to learn from him that the “Human-on-a-Chip” is one of many in vitro methods that the FDA is currently supporting to predict toxicity of therapeutic compounds. I also hope to have a chance to visit the Wyss Institute this September to learn more about this innovative new technology.