Short-Term Suspended Animation for Humans Is Coming Soon
At 1 a.m., Tony B. is flown to a shock trauma center of a university hospital. Five minutes earlier, he was picked up unconscious with no blood pressure, having suffered multiple gunshot wounds with severe blood loss. Standard measures alone would not have saved his life, but on the helicopter he was injected with ice-cold fluids intravenously to begin cooling him from the inside, and given special drugs to protect his heart and brain.
Suspended animation is not routine yet, but it's going through clinical trials at the University of Maryland and the University of Pittsburgh.
A surgeon accesses Tony's aorta, allowing his body to be flushed with larger amounts of cold fluids, thereby inducing profound hypothermia -- a body temperature below 10° C (50° F). This is suspended animation, a form of human hibernation, but officially the procedure is called Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma (EPR-CAT).
This chilly state, which constitutes the preservation component of Tony's care, continues for an hour as surgeons repair injuries and connect his circulation to cardiopulmonary bypass (CPB). This allows blood to move through the brain delivering oxygen at low doses appropriate for the sharply reduced metabolic rate that comes with the hypothermia, without depending on the heart and lungs. CPB also enables controlled, gradual re-warming of Tony's body as fluid and appropriate amounts of red blood cells are transfused into him.
After another hour or so, Tony's body temperature reaches the range of 32-34° C (~90-93° F), called mild hypothermia. Having begun the fluid resuscitation process already, the team stops warming Tony, switches his circulation from CPB to his own heart and lungs, and begins cardiac resuscitation with electrical jolts to his heart. With his blood pressure stable, his heart rate slow but appropriate for the mild hypothermia, Tony is maintained at this intermediate temperature for 24 hours; this last step is already standard practice in treatment of people who suffer cardiac arrest without blood loss trauma.
The purpose is to prevent brain damage that might come with the rapid influx of too much oxygen, just as a feast would mean death to a starvation victim. After he is warmed to a normal temperature of 37° C (~99° F), Tony is awakened and ultimately recovers with no brain damage.
Tony's case is fictional; EPR-CAT is not routine yet, but it's going through clinical trials at the University of Maryland and the University of Pittsburgh, under the direction of trauma surgeon Dr. Samuel Tisherman, who spent many years developing the procedure in dogs and pigs. In such cases, patients undergo suspended animation for a couple of hours at most, but other treatments are showing promise in laboratory animals, like the use of hydrogen sulfide gas without active cooling to induce suspended animation in mice. Such interventions could ultimately fuse with EPR-CAT, sending the new technology further into what's still the realm of science fiction – at least for now.
Consider the scenario of a 5-year-old girl diagnosed with a progressive, incurable, terminal disease.
Experts say that extended suspended animation – cooling patients in a stable state for months or years -- could be possible at some point, although no one can predict when the technology will be clinical reality, since hydrogen sulfide and other chemical tactics would have to move into clinical use in humans and prove safe and effective in combination with EPR-CAT, or with a similar cooling approach.
How Could Long-Term Suspended Animation Impact Humanity?
Consider the scenario of a 5-year-old girl diagnosed with a progressive, incurable, terminal disease. Since available treatments would only lengthen the projected survival by a year, she is placed into suspended animation. She is revived partially every few years, as new treatments become available that can have a major impact on her disease. After 35 years of this, she is revived completely as treatments are finally adequate to cure her condition, but biologically she has aged only a few months. Physically, she is normal now, though her parents are in their seventies, and her siblings are grown and married.
Such hypothetical scenarios raise many issues: Where will the resources come from to take care of patients for that long? Who will pay? And how will patients adapt when they emerge into a completely different world?
"Heavy resource utilization is a factor if you've got people hibernating for years or decades," says Bradford Winters, an associate professor of anesthesiology and critical care medicine, and assistant professor of neurological surgery at Johns Hopkins.
Conceivably, special high-tech facilities with robots and artificial intelligence watching over the hibernators might solve the resource issue, but even then, Winters notes that long-term hibernation would entail major disparities between the wealthy and poor. "And then there is the psychological effect of being disconnected from one's family and society for a generation or more," he says. "What happens to that 5-year-old waking to her retired parents and married siblings? Will her younger sister adopt her? What would that be like?"
Probably better than dying is one answer.
Back on Earth, human hibernation would raise daunting policy questions that may take many years to resolve.
Outside of medicine, one application of human hibernation that has intrigued generations of science fiction writers is in long-duration space travel. During a voyage lasting years or decades, space explorers or colonists not only could avoid long periods of potential boredom, but also the aging process. Considering that the alternative to "sleeper ships" would be multi-generation starships so large that they'd be like small worlds, human hibernation in spaceflight could become an enabling technology for interstellar flight.
Big Questions: It's Not Too Early to Ask
Back on Earth, the daunting policy questions may take many years to resolve. Society ought to be aware of them now, before human hibernation technology outpaces its dramatic implications.
"Our current framework of ethical and legal regulation is adequate for cases like the gunshot victim who is chilled deeply for a few hours. Short-term cryopreservation is currently part of the continuum of care," notes David N. Hoffman, a clinical ethicist and health care attorney who teaches at Columbia University, and at Yeshiva University's Benjamin N. Cardozo School of Law and Albert Einstein College of Medicine.
"But we'll need a new framework when there's a capability to cryopreserve people for many years and still bring them back. There's also a legal-ethical issue involving the parties that decide to put the person into hibernation versus the patient wishes in terms of what risk benefit ratio they would accept, and who is responsible for the expense and burdens associated with cases that don't turn out just right?"
To begin thinking about practical solutions, Hoffman characterizes long-term human hibernation as an extension of the ethics of cyro-preserved embryos that are held for potential parents, often for long periods of time. But the human hibernation issue is much more complex.
"The ability of the custodian and patient to enter into a meaningful and beneficial arrangement is fraught, because medical advances necessary to address the person's illness or injury are -- by definition -- unknown," says Hoffman. "It means that you need a third party, a surrogate, to act on opportunities that the patient could never have contemplated."
Such multigenerational considerations might become more manageable, of course, in an era when gene therapy, bionic parts, and genetically engineered replacement organs enable dramatic life extension. But if people will be living for centuries regardless of whether or not they hibernate, then developing the medical technology may be the least of the challenges.
DNA- and RNA-based electronic implants may revolutionize healthcare
Implantable electronic devices can significantly improve patients’ quality of life. A pacemaker can encourage the heart to beat more regularly. A neural implant, usually placed at the back of the skull, can help brain function and encourage higher neural activity. Current research on neural implants finds them helpful to patients with Parkinson’s disease, vision loss, hearing loss, and other nerve damage problems. Several of these implants, such as Elon Musk’s Neuralink, have already been approved by the FDA for human use.
Yet, pacemakers, neural implants, and other such electronic devices are not without problems. They require constant electricity, limited through batteries that need replacements. They also cause scarring. “The problem with doing this with electronics is that scar tissue forms,” explains Kate Adamala, an assistant professor of cell biology at the University of Minnesota Twin Cities. “Anytime you have something hard interacting with something soft [like muscle, skin, or tissue], the soft thing will scar. That's why there are no long-term neural implants right now.” To overcome these challenges, scientists are turning to biocomputing processes that use organic materials like DNA and RNA. Other promised benefits include “diagnostics and possibly therapeutic action, operating as nanorobots in living organisms,” writes Evgeny Katz, a professor of bioelectronics at Clarkson University, in his book DNA- And RNA-Based Computing Systems.
While a computer gives these inputs in binary code or "bits," such as a 0 or 1, biocomputing uses DNA strands as inputs, whether double or single-stranded, and often uses fluorescent RNA as an output.
Adamala’s research focuses on developing such biocomputing systems using DNA, RNA, proteins, and lipids. Using these molecules in the biocomputing systems allows the latter to be biocompatible with the human body, resulting in a natural healing process. In a recent Nature Communications study, Adamala and her team created a new biocomputing platform called TRUMPET (Transcriptional RNA Universal Multi-Purpose GatE PlaTform) which acts like a DNA-powered computer chip. “These biological systems can heal if you design them correctly,” adds Adamala. “So you can imagine a computer that will eventually heal itself.”
The basics of biocomputing
Biocomputing and regular computing have many similarities. Like regular computing, biocomputing works by running information through a series of gates, usually logic gates. A logic gate works as a fork in the road for an electronic circuit. The input will travel one way or another, giving two different outputs. An example logic gate is the AND gate, which has two inputs (A and B) and two different results. If both A and B are 1, the AND gate output will be 1. If only A is 1 and B is 0, the output will be 0 and vice versa. If both A and B are 0, the result will be 0. While a computer gives these inputs in binary code or "bits," such as a 0 or 1, biocomputing uses DNA strands as inputs, whether double or single-stranded, and often uses fluorescent RNA as an output. In this case, the DNA enters the logic gate as a single or double strand.
If the DNA is double-stranded, the system “digests” the DNA or destroys it, which results in non-fluorescence or “0” output. Conversely, if the DNA is single-stranded, it won’t be digested and instead will be copied by several enzymes in the biocomputing system, resulting in fluorescent RNA or a “1” output. And the output for this type of binary system can be expanded beyond fluorescence or not. For example, a “1” output might be the production of the enzyme insulin, while a “0” may be that no insulin is produced. “This kind of synergy between biology and computation is the essence of biocomputing,” says Stephanie Forrest, a professor and the director of the Biodesign Center for Biocomputing, Security and Society at Arizona State University.
Biocomputing circles are made of DNA, RNA, proteins and even bacteria.
Evgeny Katz
The TRUMPET’s promise
Depending on whether the biocomputing system is placed directly inside a cell within the human body, or run in a test-tube, different environmental factors play a role. When an output is produced inside a cell, the cell's natural processes can amplify this output (for example, a specific protein or DNA strand), creating a solid signal. However, these cells can also be very leaky. “You want the cells to do the thing you ask them to do before they finish whatever their businesses, which is to grow, replicate, metabolize,” Adamala explains. “However, often the gate may be triggered without the right inputs, creating a false positive signal. So that's why natural logic gates are often leaky." While biocomputing outside a cell in a test tube can allow for tighter control over the logic gates, the outputs or signals cannot be amplified by a cell and are less potent.
TRUMPET, which is smaller than a cell, taps into both cellular and non-cellular biocomputing benefits. “At its core, it is a nonliving logic gate system,” Adamala states, “It's a DNA-based logic gate system. But because we use enzymes, and the readout is enzymatic [where an enzyme replicates the fluorescent RNA], we end up with signal amplification." This readout means that the output from the TRUMPET system, a fluorescent RNA strand, can be replicated by nearby enzymes in the platform, making the light signal stronger. "So it combines the best of both worlds,” Adamala adds.
These organic-based systems could detect cancer cells or low insulin levels inside a patient’s body.
The TRUMPET biocomputing process is relatively straightforward. “If the DNA [input] shows up as single-stranded, it will not be digested [by the logic gate], and you get this nice fluorescent output as the RNA is made from the single-stranded DNA, and that's a 1,” Adamala explains. "And if the DNA input is double-stranded, it gets digested by the enzymes in the logic gate, and there is no RNA created from the DNA, so there is no fluorescence, and the output is 0." On the story's leading image above, if the tube is "lit" with a purple color, that is a binary 1 signal for computing. If it's "off" it is a 0.
While still in research, TRUMPET and other biocomputing systems promise significant benefits to personalized healthcare and medicine. These organic-based systems could detect cancer cells or low insulin levels inside a patient’s body. The study’s lead author and graduate student Judee Sharon is already beginning to research TRUMPET's ability for earlier cancer diagnoses. Because the inputs for TRUMPET are single or double-stranded DNA, any mutated or cancerous DNA could theoretically be detected from the platform through the biocomputing process. Theoretically, devices like TRUMPET could be used to detect cancer and other diseases earlier.
Adamala sees TRUMPET not only as a detection system but also as a potential cancer drug delivery system. “Ideally, you would like the drug only to turn on when it senses the presence of a cancer cell. And that's how we use the logic gates, which work in response to inputs like cancerous DNA. Then the output can be the production of a small molecule or the release of a small molecule that can then go and kill what needs killing, in this case, a cancer cell. So we would like to develop applications that use this technology to control the logic gate response of a drug’s delivery to a cell.”
Although platforms like TRUMPET are making progress, a lot more work must be done before they can be used commercially. “The process of translating mechanisms and architecture from biology to computing and vice versa is still an art rather than a science,” says Forrest. “It requires deep computer science and biology knowledge,” she adds. “Some people have compared interdisciplinary science to fusion restaurants—not all combinations are successful, but when they are, the results are remarkable.”
In today’s podcast episode, Leaps.org Deputy Editor Lina Zeldovich speaks about the health and ecological benefits of farming crickets for human consumption with Bicky Nguyen, who joins Lina from Vietnam. Bicky and her business partner Nam Dang operate an insect farm named CricketOne. Motivated by the idea of sustainable and healthy protein production, they started their unconventional endeavor a few years ago, despite numerous naysayers who didn’t believe that humans would ever consider munching on bugs.
Yet, making creepy crawlers part of our diet offers many health and planetary advantages. Food production needs to match the rise in global population, estimated to reach 10 billion by 2050. One challenge is that some of our current practices are inefficient, polluting and wasteful. According to nonprofit EarthSave.org, it takes 2,500 gallons of water, 12 pounds of grain, 35 pounds of topsoil and the energy equivalent of one gallon of gasoline to produce one pound of feedlot beef, although exact statistics vary between sources.
Meanwhile, insects are easy to grow, high on protein and low on fat. When roasted with salt, they make crunchy snacks. When chopped up, they transform into delicious pâtes, says Bicky, who invents her own cricket recipes and serves them at industry and public events. Maybe that’s why some research predicts that edible insects market may grow to almost $10 billion by 2030. Tune in for a delectable chat on this alternative and sustainable protein.
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Further reading:
More info on Bicky Nguyen
https://yseali.fulbright.edu.vn/en/faculty/bicky-n...
The environmental footprint of beef production
https://www.earthsave.org/environment.htm
https://www.watercalculator.org/news/articles/beef-king-big-water-footprints/
https://www.frontiersin.org/articles/10.3389/fsufs.2019.00005/full
https://ourworldindata.org/carbon-footprint-food-methane
Insect farming as a source of sustainable protein
https://www.insectgourmet.com/insect-farming-growing-bugs-for-protein/
https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/insect-farming
Cricket flour is taking the world by storm
https://www.cricketflours.com/
https://talk-commerce.com/blog/what-brands-use-cricket-flour-and-why/
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.