How organoid research might save lives, and curtail animal testing

Automobile crash-test dummies, when they slam into a wall at high speed, help engineers to analyze the impact, and to see how a crash would injure a live passenger. Crash-test dummies are used for safety evaluations of cars before humans ever get near them. In the same way, organoids safety-test new drugs and medicines before they ever get near a human.

Called organoids because they are miniature human organs, these tiny replicas are generated from human stem cells, and nurtured in a lab dish until they resemble real organs. Organoids including mini-kidneys, mini-livers, mini-retinas and mini-intestines have been developed. Organoids from colon cancer, pancreatic and prostate cancer patients’ stem cells are being researched.

The value of these tiny versions of organs or tumors is that new medicines can be tested on them. They are biochemical replicas of actual organs and tumors, created by using a patient’s own stem cells as seeds. They can react to new drugs the same way the donor patient’s living body would react. Indeed, the word “proxies” has been used to describe them. There will be no need for testing on animals or desperately ill human volunteers if patients’ proxies can do that for them.

In lung research, stem cells have been extracted from fibrosis patients’ lungs and placed in a lab dish, where they are nurtured to grow into realistically dimensioned fibrosis scar organoids, tiny twins of those in the actual diseased lungs. New drugs can be tested for the fibrosis patient whose cells spawned the organoid. Using patient-specific stem cells, researchers grow patient-specific organoids — personalized drug‐testing tools.

Time On Their Side

Organoids enable accurate study of a patient’s specific condition, in less time than conventional experiments take. The capacity to test drugs in a timely manner is significant. Organoid testing could take weeks or months, instead of the years that experiments currently take. Moreover, animals’ physiology does not always match humans’ — a fact that takes up time by limiting the predictive power of animal studies. Currently, organoids are being investigated for possible incorporation into treatment for Opioid Use Disorder, or OUD.

When more is learned about efficient organoid production, the time and financing needed for testing could be considerably less than that required for the conventional years-long process of achieving U.S. Food and Drug Administration approval.

Developing new drugs is costly, totaling millions of dollars, or sometimes billions, and FDA approval rates hover around 30 percent. Many medications fail in human clinical trials because they are found to be toxic, despite initial animal experiments that showed promising results. Although animal studies won’t be completely ending anytime soon, animal experiments do not replicate the genetic makeup of a human patient. Some findings are limited by their lack of transferability to a human situation. This is one part of the reason for low FDA-approval rates.

Robots built for speed

Researchers at UCLA’s Jonsson Comprehensive Cancer Center are working on developing organoids of rare, hard-to-treat cancers, and speed is the name of their game.

Using their new technique, surgeons extract patients’ tumor stem cells and that same day the researchers seed them in the lab, where they generate tumor organoids, typically within five days. After multiple tumor organoids develop, the researchers test them for hundreds of drugs to determine which ones are effective, in an automated feed. Instead of testing one drug at a time, robots simultaneously test hundreds of different treatments. The process can take less than two weeks.

Prescribed drugs work differently for everyone, depending upon the particular biochemistry of the patient. For rare cancers, science has few treatments and patients have few options. The use of robots to quickly identify rare-tumor treatment may upend that destiny.

All together now

One roadblock to advancement has been organoids’ detachment from the body. A living organ such as the pancreas or kidney entwines with the blood system, the nervous system and muscles that anchor it. The effectiveness of a new drug can depend upon the health of neighboring body parts.

Conversely, an organoid is a lone ranger, detached from related body parts. To lessen organoids’ separateness, scientists are placing organoids on polymer chips, and then joining multiple organoids-on-chips together into “bodies-on-chips.”

Multiple organoids linked together means that the various organoids duplicating various organs can communicate with each other — just as a fractured bone will impact any organs or nerves that border it.

Bodies-on-chips can yield assessment of the impact of treating one organ on other organs. An experimental medicine for liver disease might seem effective when tested on a single liver organoid, but could be found to hurt other organoids when they are all tested together.

Poised On The Ethical Frontier

The thalamus is part of the brain known as the “traffic cop of the brain.” The job of the thalamus is to gather incoming information from the eyes, ears and other sensory organs and then send that information on to different routes into the brain for processing. Yale University researchers have created a thalamus organoid, in an effort to demystify some origins of neuropsychiatric diseases. They are curious about the thalamus because it might be involved in epilepsy, autism spectrum disorder, schizophrenia and depression. Many other scientists worldwide are also creating brain organoids with the same goals.

Medical innovations often arrive astride debate. People are “not going to get upset about making a pancreas,” one expert has said. “But the closer you come to making a human brain, the more issues get raised.” One critic pointed to a moral quandary: “A human brain that was ‘fully working’ would be conscious, have hopes, dreams, feel pain, and would ask questions about what we were doing to it.”

Would a brain organoid be capable of conscious experience? If so, will it get protections given to human or animal subjects? What about Big Data, with regard to data sharing, legacy use of brain tissue, or a patient’s memory cells? What about funding? Although investment can spark medical advances, “profit-making out of human tissues is ethically contentious.” Ironically, the science that could fuel the end of animal-testing simultaneously spawns new ethical challenges.

The whiff of Frankenstein notwithstanding, many ethics experts agree that organoid research should continue moving forward, albeit with great caution, because of its potential for saving lives — both animal and human.