The ceremony takes place on the night of the full moon in February, which the Tibetans celebrate as the coldest of the year. Buddhist monks clad in light cotton shawls climb to a rocky ledge some 15,000 feet high and go to sleep, in child’s pose, foreheads pressed against cold Himalayan rocks. In the dead of the night, temperatures plummet below freezing but the monks sleep on peacefully, without shivering.
Footage of the ritual exists from the winter of 1985 when a team of medical researchers led by Herbert Benson, a Harvard cardiologist, were allowed in as observers at a monastery just outside the town of Upper Dharamsala in northern India.1 Benson had the blessing of the Dalai Lama, with whom he had developed a friendship; the physician was driven to understand the physiological mechanisms that allowed the monks to survive the night. Their bodies had entered a state that required years of meditative and physical practice that the Dalai Lama called miraculous. Had Benson’s research taken place today, it is very likely he would have called it “biostasis.”
Our bodies run a very tight ship. To keep living, we need a constant supply of oxygen, and our temperature is allowed to fluctuate within narrow limits. A fever can turn deadly, as can severe hypothermia. Healthy bodies have a steady heartbeat and a dependable oxygen consumption rate, which physicians use as a measurement of metabolism. If the life burning within us is a symphony, then metabolism is its score—the perfect sum of all the chemical reactions that take place inside our cells, carefully orchestrated.
If the life burning within us is a symphony, then metabolism is its score.
Until recently, at least from the perspective of Western medicine, life’s tempo was considered non-negotiable. The change in outlook has come from an unusual initiative, a program led by the Defense Advanced Research Projects Agency (DARPA), which supports the United States military. Over the past five years, DARPA has funded research into biostasis, which aims to bring the metabolic symphony to a halt, before resuming the score some indefinite time later, exactly where it left off.
One promise of the DARPA biostasis research is a state of suspended animation or physiological stability, delivered in the form of a drug, rather than through years of meditative practice. This would differ from anesthesia by acting on all human tissues equally, rather than suspending only consciousness and pain. Biostasis aims to snap-freeze the whole body, without the cooling.
With biostasis, DARPA planted a flag in uncharted medical territory, asking researchers to reach beyond normal health. Tristan McClure-Begley, a former program manager at DARPA, who founded the biostasis project, explained its key impetus was extending the “golden hour”—the period immediately after a severe injury when medical and surgical treatment could prevent death. With head and spinal cord traumas in particular, irreparable damage accrues if aid is delayed. A biostatic delivered on the battlefield could buy time for fallen soldiers, improving their chances of survival.
DARPA issued a call to fund researchers to develop a biostasis drug, and the Wyss Institute for Biologically Inspired Engineering at Harvard University is one of the teams that answered. “This DARPA call was fun because it was so out there,” said Don Ingber, founding director of the Institute and a chaired professor at Harvard’s medical and engineering schools. “There was no place to start, no drug target or screen to implement,” he added. It is remarkable that in the absence of academic precedent or a history of research to draw on, the first successful biostasis drug was proposed earlier this year.2
SNC80, the name that the small-molecule drug is known by, was first tested on Xenopustadpoles. The cold-blooded amphibian embryos are easy to manipulate in the lab and are useful models for approximating human nervous and immune systems. They have a large bulbous head with a brain and spinal cord and a tail for swimming. The tadpoles have a beating heart, gills, and intestines. The core organs are important as indicators for what may happen to an equivalent human organ, whereas the tadpoles’ swimming ability sets up a quick and easy screen for biostasis.
A minute dose of the chemical, which permeated the translucent skin of the tadpoles, slowed down their swimming, halved their heart rate and brought their oxygen consumption—the gold standard for measuring metabolic rate—to one third of baseline. Most importantly, the effects were reversible. Within an hour of the drug being drained, the tadpoles went back to briskly swimming around petri dishes. To the best of the researchers’ knowledge, no core organs of the tadpoles were adversely affected by the drug.
Megan Sperry, a postdoctoral fellow at the Wyss Institute, who led the tadpole research, explained that molecules of SNC80 were able to penetrate all tadpole tissues, including their guts, gills, and skeletal muscles. Here was a drug that impacted the whole organism, likely tinkering with something critically central to biology, which acted to arrest all biological processes indiscriminately. It was later found that SNC80 works to slow down mitochondria, the power houses of all cells, arresting metabolic processes without killing tissues. Importantly, Sperry said, the drug did not “induce toxicities.”
Reversibly shutting down metabolism is not unheard of in nature. Much of the bio-inspiration came from digging deep into ecological studies of hibernating animals. Species such as brown bears living in Alaska can actively shift their metabolism into a lower gear for winter, slowing their heart rate to four beats per minute and dropping their body temperature to below 40 degrees Fahrenheit. The visually unassuming wood frog Rana sylvatica can go as far as completely freezing solid to skip the arctic winter season.
What did the scientist think of the monks who slowed their own metabolism?
Perhaps the most impressive feat of biostasis, which has not escaped DARPA’s attention, is performed by the spiny desert mouse. With rounded ears, dark oil-slick eyes, and a golden coat, it has capabilities worthy of DC superheroes. Not only is the spiny desert mouse the only mammal known to be capable of tissue regeneration, growing back skin, sweat glands, fur, and even cartilage with little to no scarring when a predator takes off a bite, in times of extreme need it can go into full body torpor for six to seven hours at a time. It can do this in the heat of the African desert, a rare example of torpor as a response to hot rather than cold temperatures.
The greatest challenge with developing a biostasis drug for humans is finding a chemical that can act on the whole body, affecting a variety of tissues and organs gently but profoundly. The Harvard team tested the impact of SNC80 on “organs-on chips,” microchip devices with tiny channels lined with living human organ cells. They also tested its impact on select human tissue cultures, including the gut and the liver, as well as on whole pig organs and limbs. The effects were remarkable—a viable pig heart could be preserved for twice as long as it could using traditional preservation techniques that rely on mechanical cooling. “And a pig heart is almost as big as a human heart, Ingber said. “So that’s probably the most impressive thing we’ve done.”
The perfect biostasis drug would be something that doesn’t affect the harmonies of metabolic processes, and the complex wiring that integrates different tissues of a body into a single whole. Ingber admits SNC80 is not that perfect drug. But as is often the case with drug development, the experiments have been a good start. SNC80 is the “first step toward compounds that reversibly slow down metabolism,” Ingber said. “And we have already identified new versions of the molecule that are more potent. This one works at the level of tissues and individual organs.” The next step would be to get the drug to work on the whole person.
Herbert was able to convince the Tibetan monks he had observed in the remote Rumtek Monastery to participate in a medical study.3 Sitting cross-legged in a large unheated ceremonial room the monks consented to wearing special face masks during their daily meditation, connected to a respirometer. This allowed the physicians to collect small quantities of expired air during their breathing, which they analyzed for oxygen content. Strikingly, they found that during several different meditative practices, resting metabolism “could be both raised (up to 61 percent) and lowered ([by] 64 percent),” the latter of which is on par with the effects of SNC80 on Xenopus tadpoles.
I asked Ingber what he thought about the monks, who showed that metabolism in the whole human body could be slowed. “At some high level, you’re probably right that there’s a nervous system involvement in all this,” he said. “But oxygen utilization is only one part of metabolism. A Tibetan monk will be awakened if you tap on him. So it’s not exactly a torpor state, but it’s certainly the first step toward slowing metabolism, which can be done for short times.”
The initial goal of biostasis research—a state of suspended animation that can last as long as it takes to reach distant planets or survive beyond the “golden hour” after catastrophic injury—remains out of reach. But not entirely. We are, after all, animals ourselves. “The way I see it,” Ingber said, “is that animals like the Alaskan ground squirrel can go into torpor and don’t need to eat for extended times. Bears can hibernate. I was just thinking this summer about hummingbirds and butterflies. They go into torpor every evening.”
As scientists continue to work on a therapy to induce humans into a full-body torpor, maybe they should take another close look at the ceremony of Tibetan monks, meditating in the winter cold. They look as peaceful and content as butterflies.
1. From the documentary, Advanced Tibetan Buddhist Meditation: The Investigations of Herbert Benson, M.D., by filmmaker Russell Pariseau.
2. Sperry, M.M., et al. Identification of a pharmaceutical biostasis inducer that slows metabolism in multiple vertebrates that do not hibernate. bioRxiv (2023).
3. Benson, H., Malhotra, M.S., Goldman, R.F., Jacobs, G.D., & Hopkins, P.J. Three case reports of the metabolic and electroencephalographic changes during advanced Buddhist meditation techniques. Behavioral Medicine 2, 90-95 (1990).