Bay Area-based R3 Bio has been quietly pitching the idea to investors and industry publications as a way to replace lab animals without the ethical issues that come with living organisms. This is because these structures will contain all the specialized organs except the brain, rendering them unable to think or feel pain. Co-founder Alice Gilman says the company’s long-term goal is to create a human version that can be used as a source of tissues and organs for people who need them.
For Immortal Dragons, a Singapore-based longevity fund that has invested in R3, the idea of replacement is a core strategy for human longevity. “We think replacement is probably better than repair when it comes to treating diseases or regulating the aging process in the human body,” says CEO Boyang Wang. “If we could create a nonfunctional, headless bodyoid for a human, that would be a great source of organs.”
For now, R3 aims to make monkey organ sacks. “The advantage of using models that are more ethical and are organ system specific is that the test can be meaningfully more scalable,” Gilman says. (The name R3 comes from the philosophy of animal research known as the three R’s—replacement, reduction, and refinement) developed by British scientists William Russell and Rex Birch in 1959 to promote human experimentation.
New drugs are often tested on monkeys before being given to human participants in clinical trials. For example, monkeys were crucial for testing vaccines and treatments during the COVID-19 pandemic. But they are also an expensive resource, and their numbers in the US are declining after China banned the export of non-human primates in 2020.
Animal rights activists have long pushed for an end to research on monkeys, and one of seven federally funded primate research facilities nationwide has indicated it will consider closing and moving to a sanctuary amid growing pressure. The US Centers for Disease Control and Prevention is also shutting down monkey research, part of a larger trend by the government to reduce reliance on animal testing.
As a result, Gilman says, there are not enough research monkeys left in the US to allow the necessary research if another pandemic threat emerges. Enter organ sacks.
Theoretically organ sacs would offer advantages over existing organ-on-chips or tissue models, which lack the full complexity of entire organs, including blood vessels.
Gilman says it’s already possible to create rat organ bags that don’t have a brain, though he and co-founder John Schloendorn deny that R3 has created them. (For the record, Gilman doesn’t like the term “brainless” to describe organ sacks. “There’s nothing missing,” she says, “because we just designed it to do the things we want.) Gilman and Schloendorn wouldn’t say how exactly they plan to create monkey and human organ sacks, but they said they’re exploring a combination of stem-cell technology and gene editing.
Paul Knoepfler, a stem cell biologist at the University of California, Davis, says it is plausible that organ sacks could be developed from induced pluripotent stem cells. These stem cells come from adult skin cells and are reprogrammed to an embryo-like state. They have the ability to form any cell or tissue in the body and are used to create embryo-like structures that resemble the real thing. By editing these stem cells, scientists can deactivate genes essential for brain development. The resulting embryo can be incubated until it develops into organized organ structures.
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