Typically, animals are the first stop in seeing how a drug works, and researchers use them to see how well it is absorbed, distributed and metabolized in the body. But animal testing often doesn’t translate well to humans, and it also carries a high financial—and ethical—cost.
In 2010 a team at the Wyss Institute at Harvard offered an alternative with their first “organ on a chip.” The devices are the size of a computer memory stick and contain living cells from human organs. Those cells are cultured on one side of a porous membrane, and vascular tissue cells line the other, allowing the two compartments to exchange molecules—including drugs—as they would in the human body.
In early 2020, the teams hit their target to have a complete human “body on chips,” which would consist of at least ten types of organs. By sending fluids from one chip to another—which is done by a device they call “the interrogator”—the researchers can explore the multisystem effects of drugs on real human tissues. The model has already delivered critical insights about how particular compounds might work in the body and where they might prove toxic. Their use in the future as a first stop for experimental drugs may pay big dividends, improving the success rate of those that make it into human clinical trials.
Chips with human tissue, developed over the past 10 years, can demonstrate the multisystem effects of experimental drugs.
Chips with human tissue, developed over the past 10 years, can demonstrate the multisystem effects of experimental drugs.
Chips with human tissue, developed over the past 10 years, can demonstrate the multisystem effects of experimental drugs.
Proof of Concept Study (2020)
The first organ chip, which modeled a human lung, was developed in 2010. In 2012 the organization that funds breakthrough technologies that might help with national security, DARPA, issued a challenge to create such chips for each of the major organs and the technology to replicate multi-organ system responses. In January the Wyss Institute published a study showing that it had achieved this goal. In their experiment, the group linked eight chips, passed blood substitute among them and correctly predicted the distribution of a particular chemical over the course of three weeks.
Nicotine Metabolism Study (2020)
Nicotine chewing gum, an anti-smoking aid, is also being investigated as a drug that might help with neurodegenerative and inflammatory bowel diseases. To study its effects in the body, researchers coupled a human gut chip with liver and kidney chips. They could study nicotine’s first pass through the intestinal wall, through the vascular system, to the liver where it is metabolized, and finally to the kidney where it is excreted. The researchers were able to quantify the concentration of nicotine metabolites in each organ and to quantitatively predict the drug’s pharmacokinetics—the way drug levels change in blood over time—which closely matched data from human studies.
Cisplatin Study (2020)
The team also investigated the pharmacological effects of cisplatin, a chemotherapeutic drug commonly used in cancer treatments. It is administered intravenously and can be toxic to the kidneys and bone marrow. When researchers linked a bone marrow chip to the liver and kidney chips, the model accurately predicted changes of cisplatin levels in blood over time and cisplatin breakdown products in the system. It also accurately predicted the toxicity of the drug in the bone marrow, matching data from previous clinical studies in humans.
