Cortical neuron staining in the Emulate Brain-Chip. Image courtesy of Emulate Inc.
Engineered microchips with living human cells have the potential to accelerate drug development and replace animal testing, said Dr. Donald Ingber, the founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard University.
The organ-on-a-chip technology could also enable the industry to rethink its business model, Ingber said in a webinar from the Boston-based startup Emulate. While critics routinely criticize the pharmaceutical industry for price gouging, the blockbuster business model’s demise has threatened many firms’ profitability in the sector. R&D costs are another pressure. “It costs over $3 billion to go from the bench to the clinic at this point,” said Dr. Donald Ingber, the founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard University.
Animal studies are a related challenge for the industry. Not only are they “extremely slow,” and pose “major ethical issues,” they frequently don’t predict clinical responses. “We’re talking 70–90% failure rates based on what came out of animal predictions in various different areas,” Ingber said.
The Wyss Institute helped develop organs-on-chips — engineered microchips with living human cells to mimic organ functions — to address these hurdles. A decade ago, Wyss researchers developed a breathing lung on a chip. “We’re trying to create what I like to think of as living three-dimensional cross sections through a major functional unit that will provide a window on a molecular scale [to] living cells inside human tissues and organ structures,” Ingber said.
Emulate, a Wyss spinoff, is working on commercializing such organs-on-chips and corresponding disease models. For the lung chip, Wyss developed models for pulmonary edema, pulmonary thrombosis and drug toxicity. The latter has enabled researchers to mimic the toxicity of drugs that did not appear in animal trials. Wyss scientists have also used the technology to discover new therapeutic targets. A Phase 2 trial is underway related to the technology.
The respiratory models have grown more complex over time. Wyss researchers are using a lung airway chip for COVID-19 therapeutics discovery.
The researchers have also developed an intestine chip that can support a “complex living microbiome composed of hundreds of different types of bacteria,” Ingber said.
They have also created a bone-marrow chip.
A blood-brain barrier chip can help identify strategies to deliver drugs to the brain selectively. “But the ultimate goal is really to recapitulate human pathophysiology. Because this is where disease modeling is where animal models really fail, and to predict human responses to drugs using clinically relevant dose exposures.”