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As the Trump administration phases out the use of animal experimentation across the federal government, a biotech startup has a bold idea for an alternative to animal testing: nonsentient “organ sacks.” Bay Area-based R3 Bio has been quietly pitching the idea to investors and in industry publications as a way to replace lab animals without the ethical issues that come with living organisms. That’s because these structures would contain all of the typical organs—except a brain, rendering them unable to think or feel pain. The company’s long-term goal, cofounder Alice Gilman says, is to make human versions that could be used as a source of tissues and organs for people who need them. For Immortal Dragons, a Singapore-based longevity fund that’s 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 can create a nonsentient, headless bodyoid for a human being, that will be a great source of organs.” For now, R3 is aiming to make monkey organ sacks. “The benefit of using models that are more ethical and are exclusively organ systems would be that testing can be meaningfully more scalable,” Gilman says. (R3’s name comes from the philosophy in animal research known as the three R’s—replacement, reduction, and refinement—developed by British scientists William Russell and Rex Burch in 1959 to promote humane experimentation.) New drugs are often tested in monkeys before they’re given to human participants in clinical trials. For instance, monkeys were critical during the Covid-19 pandemic for testing vaccines and therapeutics. But they’re also an expensive resource, and their numbers are dwindling in the US after China banned the export of nonhuman primates in 2020. Animal rights activists have long pushed to end research on monkeys, and one of the seven federally funded primate research facilities across the country has signaled it would consider shutting down and transitioning into a sanctuary amid growing pressure. The US Centers for Disease Control and Prevention is also winding down monkey research, part of a bigger trend across the government to reduce reliance on animal testing. As a result, Gilman says, there aren’t enough research monkeys left in the US to allow for necessary research if another pandemic threat emerges. Enter organ sacks. Organ sacks would in theory offer advantages over existing organs-on-chips or tissue models, which lack the full complexity of whole organs, including blood vessels. Gilman says it’s already possible to create mouse organ sacks that lack a brain, though she and cofounder John Schloendorn deny that R3 has made them. (For the record, Gilman doesn’t like the term “brainless” to describe the organ sacks. “It's not missing anything, because we design it to only have the things we want,” she says.) Gilman and Schloendorn would not say how exactly they plan to create the monkey and human organ sacks, but said they are exploring a combination of stem-cell technology and gene editing. It’s plausible that organ sacks could be grown from induced pluripotent stem cells, says Paul Knoepfler, a stem cell biologist at the University of California, Davis. These stem cells come from adult skin cells and are reprogrammed to an embryonic-like state. They have the potential to form into any cell or tissue in the body and have been used to create embryo-like structures that resemble the real thing. By editing these stem cells, scientists could disable genes needed for brain development. The resulting embryo could then be incubated until it grows into organized organ structures. Gilman envisions monkey organ sacks initially being used for drug toxicity testing. Eliminating pain and suffering that research animals experience is a major motivation for the startup. The US Animal Welfare Act requires minimizing pain and distress for research animals, but it’s not always possible. In fiscal year 2024, US research facilities reported using more than 60,000 nonhuman primates for testing and experimentation, according to the Animal and Plant Health Inspection Service, part of the Department of Agriculture. More than 33,000 of those animals were not subjected to pain, while nearly 26,000 experienced minimal pain. For about 1,200 of those animals, pain was not minimized due to the nature of the experiments. The federal government does not keep statistics on how many nonhuman primates are euthanized every year as a result of research. R3’s ambitions go beyond replacing animal testing, though. The company is eyeing replacement of human parts, an emerging idea in the longevity field. The startup aims to create nonsentient human organ sacks that could provide blood, tissue, and organs to people when their own bodies fail them. “We have things that no one has invented before to create designer organs,” says Gilman, wh