It has been 200 years since Mary Shelley's Frankenstein was published, and while scientists still haven't figured out how to create a walking, talking complex life in a lab, they may be getting closer.
A growing number of researchers are mastering the creation of organoids: simplified, miniature versions of real human organs. These structures aren't being harvested to make Frankenstein's monster. Instead, they're helping develop new drugs, and they are forcing the medical establishment to seriously consider the ethics of lab-grown life.
Developing pharmaceuticals is typically an expensive and risky process. Roughly 90 percent of drugs that make it to human trials are never submitted to the FDA for approval because they're found to be unsafe or ineffective. Most estimates place the cost of developing a new drug at somewhere around $3 billion. Organoids, which are grown from human stem cells, may be able to remove some of the guesswork in patient trials.
"Researchers have gotten really good at curing diseases in mice, but unfortunately animal studies don't really translate to human bodies," says Kevin Costa, chief scientific officer at Novoheart, a stem cell biotechnology firm known for creating heart organoids. "There are differences in how cardiac muscle cells behave in rodents versus primates and humans. Consequently, one of the main reasons that drugs fail in clinical trials is because of cardiotoxicity, problems related to heart function."
Novoheart's miniature beating hearts can be designed to reflect healthy heart function, or they can reproduce the genetic abnormalities of a patient who originally donated their cells. These heart models can then be used by pharmaceutical companies in preclinical testing to determine the safety and efficacy of a potential treatment. While the organoids aren't nearly as complex as a full-sized heart, the idea is to utilize human-specific models when forecasting drug effects.
Understanding potential side effects is also key when developing a new drug. Side effects are rarely confined to a single organ system, which is why Costa believes connecting organoids is the logical next step. Late last year, Novoheart also filed a patent for a modular "bioreactor" that scientists can use to monitor multiple organoids at once. This means a number of different mini organs — from kidneys to brains — could be linked up to simulate drug reactions that occur throughout the body.
"Heart tissue doesn't behave in isolation," he explains. "There are interactions at the systems level between the heart and other organs in the body, and if we ultimately want to realize the potential for replacing animal studies with human-based organoids, then we need to start to create systems comprised of different organ types."
But things begin to stray into Frankenstein territory when scientists talk about designing realistic miniature brains. Earlier this month, researchers from the University of California, San Diego revealed they had grown organoids that spontaneously produced human-like brain waves for the first time. The electrical patterns observed by biologist Alysson Muotri and his team resembled those of infants born at 25 to 39 weeks' gestation.
There are important differences between these lab-grown brains and their real-life counterparts. First of all, they don't yet contain all of the cell types found in the cerebral cortex, which is the part of the brain responsible for cognition and awareness. Second, they don't have connections to other brain regions. But the very existence of electrical waves in these organoids raises uncomfortable questions about whether they could develop consciousness.
"Right now, you can grow organoids for over a year, but it's difficult to get them to the point where their size and capacity matches the real human brain," says Insoo Hyun, a professor of bioethics and philosophy at Case Western Reserve University. "As you meet short-term research goals, such as maintenance and growth, and attain a full complement of cell types, you're potentially getting closer to having conscious brains in a dish."
The medical establishment isn't currently trying to create consciousness, but these new brain organoids could effectively be drawing a roadmap for doing just that. According to Hyun, international stem cell research guidelines don't presently require close scrutiny of brain organoid work. "If you're making something that looks like an embryo model, then it needs to be reviewed," he explains. "But if you're using brain organoids to do drug screenings, it flies under the radar."
In other words, scientists may want to proceed with caution. In September, Hyun and a team of scientists from Harvard, Stanford, and MIT launched a study to identify ethical issues in the emerging field of brain bioengineering. The Brainstorm Project is designed to be the first step in building a philosophical framework that will guide regulations and policies around brain organoids. "This is such a new field that we want to map out the terrain of what is permissible and identify whether there are things we wouldn't want people to do with organoids," Hyun says.
Biologically speaking, we still have a way to go before we can make conscious brains in the lab. In a way, that's a relief. But the development of complex human tissue is no longer a thing of science fiction — it is fast becoming a real-life ethical minefield.