“Chip”ping Away Obstacles to Drug Discovery

10 years and 1 billion dollars. That is the estimated time and cost to bring a drug from discovery to the market. Despite advances in our knowledge and technological capabilities, drug discovery remains the most challenging and riskiest undertaking in the pharma industry. One of the primary obstacles is successfully translating drug candidates from cell culture and animal models into clinical trials. This is because there is an inherent disconnect between cells grown in a petri dish and model organisms (i.e. mice, rats, dogs) to human physiology. “Animals such as the rodent are only 30-70% predictive of human toxicity,” says D. Lansing Taylor, Director of the University of Pittsburgh Drug Discovery Institute [1]. Because of this dissimilarity, only 10% of drugs that enter clinical trials are ultimately approved [2]. One way to increase the efficiency of drug discovery is to more effectively model human physiology during early stages of drug discovery. This previously unattainable goal is quickly becoming a reality, thanks to a new technology called Organs-on-Chips.

Organs-On-Chips are clear and flexible polymer microchips the size of a USB memory stick and contain microfluidic channels coated with cells. These cells originate from specific body tissues and are supplemented with a synthetic circulatory system containing oxygen, nutrients, and potential drug candidates. The 3-D architecture of these chips allows scientists to recapitulate the structure of human organs and tissues like blood vessels, lung alveoli, or kidney tubules. This design is so revolutionary that it was the first medical device to be named Design of the Year by curators at the London Design Museum and has been included in the New York Museum of Modern Art. The senior curator at the MoMA, Paola Antonelli, commented, “…not only is the form striking, but so is the function – the idea behind the object. [3]”

This technology was pioneered by Dr. Donald Ingber at Harvard’s Wyss Institute for Biologically Inspired Engineering and was first published in 2010. For Ingber, Organs-On-Chips efficiently represent the dynamic relationship in biology between form and function that is impossible to recreate in cells grown on a plate. “Design in its greatest simplicity is minimizing any system down to its elements so as to have the greatest impact. [3]” For example, the lung-on-a-chip mimics alveoli by growing human lung cells on one side of a porous membrane, with capillary cells on the other half. Air is passed through a microscopic channel over the lung cells while blood is passed underneath the capillary cells to carry away oxygen (see figure). Additionally, vacuum pressure can be used to mimic the mechanical pressure of breathing. Ingber’s lung-on-a-chip has been able to recapitulate bacterial infection and pulmonary edema. Dr. Geraldine Hamilton, previously a senior staff scientist at the Wyss, says, “We are trying to create an environment where they can function like they would in the body. [1]” Hamilton is currently advancing Organs-on-chips technology as the President and CSO of Emulate.

Figure from [1]

Additionally, Ingber says, “Most drug companies get completely different results in dogs, cats, mice and humans, but now they will be able to test the specific effects of drugs with greater accuracy and speed. [4]” Danilo Tagle, associate director at the National Center for Advancing Translational Sciences at the NIH, says, “You can go forward with a candidate drug with greater assurance and confidence that it will have the desired effect on humans. [5]” The FDA is also willing to consider data from Organs-On-Chips in place of animal models, given proper validation.

Looking forward, the goal is to combine multiple Organs-On-Chips to model an entire human. Researchers at the Wyss Institute have already designed Organs-On-Chips for 12 different organs, and have been able to couple lung-liver and lung-heart chips to one another. As Dr. Taylor says, “These platforms are designed to be as close to human as you can get, but enable experimental manipulation. [6]” Researchers are also pushing this technology into industrial drug discovery, with scientists from Emulate working with Johnson and Johnson to incorporate Organs-On-Chips into pre-clinical drug development.

Come hear about the future of this disruptive new technology and its impacts on research and drug discovery on Sept. 15 at MIT's Stata Center! Biotech Connection Boston is proud to host the pioneers of Organs-On-Chips: Dr. Donald IngberDr. Geraldine Hamilton (President and CSO at Emulate), and Dr. Peggy Guzzie-Peck (Global Head of Investigative Safety Sciences). John Carroll, editor of FierceBiotech will be moderating the panel discussion. Free registration opens at 6 PM, followed by an in-depth panel discussion with audience Q&A. This event is hosted by the MIT Biotech club and sponsored by our partners at Charles River Laboratories, the Wyss Institute, and BioPharma Dive. We will also feature exhibitions from VWR, Qiagen, AET Labs, and DiscoveRx during the networking reception.

Works Cited

[1] Janna Lawrence (2014) 'Organ-on-chip technology to revolutionise drug development' The Pharmaceutical Journal 16th August, Retrieved [15th August 2015] http://www.pharmaceutical-journal.com/news-and-analysis/feature/organ-on-chip-technology-to-revolutionise-drug-development/20065894.article

[2] The Independent Institute, Retrieved [15th August 2015] http://www.fdareview.org/approval_process.shtml

[3] Liz Stinson (2015) 'A Chip That Mimics Human Organs is Design of the Year' Wired 23rd June, Retrieved [15th August 2015] http://www.wired.com/2015/06/chip-mimics-human-organs-design-year/

[4] Oliver Wainwright (2015) 'The end of animal testing? Human-organs-on-chips wins design of the year' The Guardian 22nd June, Retrieved [15th August 2015] http://www.theguardian.com/artanddesign/2015/jun/22/the-end-of-animal-testing-human-organs-on-chips-win-design-of-the-year

[5] Jessica Firger (2015) 'Organ-on-chip could revolutionize drug testing' Newsweek 4th July, Retrieved [15th August 2015] http://www.newsweek.com/organ-chip-could-revolutionize-drug-testing-349950

[6] Alexander Gelfand (2015) 'Building a Full-Blown Human Body-on-a-chip' Discover 30th April, Retrieved [15th August 2015] http://discovermagazine.com/2015/june/4-pieces-of-me