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Yale scientists restore cellular function in 32 dead pig brains
Researchers hope the technology will further our understanding of the brain, but lawmakers may not be ready for the ethical challenges.
- Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.
- They hope the technology will advance our understanding of the brain, potentially developing new treatments for debilitating diseases and disorders.
- The research raises many ethical questions and puts to the test our current understanding of death.
The image of an undead brain coming back to live again is the stuff of science fiction. Not just any science fiction, specifically B-grade sci fi. What instantly springs to mind is the black-and-white horrors of films like Fiend Without a Face. Bad acting. Plastic monstrosities. Visible strings. And a spinal cord that, for some reason, is also a tentacle?
But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.
What's dead may never die, it seems
The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.
BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.
The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.
As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.
The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.
"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.
An ethical gray matter
Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.
The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.
Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.
Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?
"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."
One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.
The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.
"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.
It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.
Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?
The dilemma is unprecedented.
Setting new boundaries
Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."
She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.
- Why Cryogenics Is Bogus - Big Think ›
- Factory farm death rate of pig sows increases sharply - Big Think ›
The COVID-19 pandemic is making health disparities in the United States crystal clear. It is a clarion call for health care systems to double their efforts in vulnerable communities.
- The COVID-19 pandemic has exacerbated America's health disparities, widening the divide between the haves and have nots.
- Studies show disparities in wealth, race, and online access have disproportionately harmed underserved U.S. communities during the pandemic.
- To begin curing this social aliment, health systems like Northwell Health are establishing relationships of trust in these communities so that the post-COVID world looks different than the pre-COVID one.
COVID-19 deepens U.S. health disparities<p>Communities on the pernicious side of America's health disparities have their unique histories, environments, and social structures. They are spread across the United States, but they all have one thing in common.</p><p>"There is one common divide in American communities, and that is poverty," said <a href="https://www.northwell.edu/about/leadership/debbie-salas-lopez" target="_blank">Debbie Salas-Lopez, MD, MPH</a>, senior vice president of community and population health at Northwell Health. "That is the undercurrent that manifests poor health, poor health outcomes, or poor health prognoses for future wellbeing."</p><p>Social determinants have far-reaching effects on health, and poor communities have unfavorable social determinants. To pick one of many examples, <a href="https://www.npr.org/2020/09/27/913612554/a-crisis-within-a-crisis-food-insecurity-and-covid-19" target="_blank" rel="noopener noreferrer">food insecurity</a> reduces access to quality food, leading to poor health and communal endemics of chronic medical conditions. The U.S. Centers for Disease Control and Prevention has identified some of these conditions, such as obesity and Type 2 diabetes, as increasing the risk of developing a severe case of coronavirus.</p><p>The pandemic didn't create poverty or food insecurity, but it exacerbated both, and the results have been catastrophic. A study published this summer in the <em><a href="https://link.springer.com/article/10.1007/s11606-020-05971-3" target="_blank">Journal of General Internal Medicine</a></em> suggested that "social factors such as income inequality may explain why some parts of the USA are hit harder by the COVID-19 pandemic than others."</p><p>That's not to say better-off families in the U.S. weren't harmed. A <a href="https://voxeu.org/article/poverty-inequality-and-covid-19-us" target="_blank" rel="noopener noreferrer">paper from the Centre for Economic Policy Research</a> noted that families in counties with a higher median income experienced adjustment costs associated with the pandemic—for example, lowering income-earning interactions to align with social distancing policies. However, the paper found that the costs of social distancing were much greater for poorer families, who cannot easily alter their living circumstances, which often include more individuals living in one home and a reliance on mass transit to reach work and grocery stores. They are also disproportionately represented in essential jobs, such as retail, transportation, and health care, where maintaining physical distance can be all but impossible.</p><p>The paper also cited a positive correlation between higher income inequality and higher rates of coronavirus infection. "Our interpretation is that poorer people are less able to protect themselves, which leads them to different choices—they face a steeper trade-off between their health and their economic welfare in the context of the threats posed by COVID-19," the authors wrote.</p><p>"There are so many pandemics that this pandemic has exacerbated," Dr. Salas-Lopez noted.</p><p>One example is the health-wealth gap. The mental stressors of maintaining a low socioeconomic status, especially in the face of extreme affluence, can have a physically degrading impact on health. <a href="https://www.scientificamerican.com/index.cfm/_api/render/file/?method=inline&fileID=123ECD96-EF81-46F6-983D2AE9A45FA354" target="_blank" rel="noopener noreferrer">Writing on this gap</a>, Robert Sapolsky, professor of biology and neurology at Stanford University, notes that socioeconomic stressors can increase blood pressure, reduce insulin response, increase chronic inflammation, and impair the prefrontal cortex and other brain functions through anxiety, depression, and cognitive load. </p><p>"Thus, from the macro level of entire body systems to the micro level of individual chromosomes, poverty finds a way to produce wear and tear," Sapolsky writes. "It is outrageous that if children are born into the wrong family, they will be predisposed toward poor health by the time they start to learn the alphabet."</p>Research on the economic and mental health fallout of COVID-19 is showing two things: That unemployment is hitting <a href="https://www.pewsocialtrends.org/2020/09/24/economic-fallout-from-covid-19-continues-to-hit-lower-income-americans-the-hardest/" target="_blank" rel="noopener noreferrer">low-income and young Americans</a> most during the pandemic, potentially widening the health-wealth gap further; and that the pandemic not only exacerbates mental health stressors, but is doing so at clinically relevant levels. As <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413844/" target="_blank" rel="noopener noreferrer">the authors of one review</a> wrote, the pandemic's effects on mental health is itself an international public health priority.
Working to close the health gap<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDc5MDk1MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxNTYyMzQzMn0.KSFpXH7yHYrfVPtfgcxZqAHHYzCnC2bFxwSrJqBbH4I/img.jpg?width=980" id="b40e2" class="rm-shortcode" data-rm-shortcode-id="1b9035370ab7b02a0dc00758e494412b" data-rm-shortcode-name="rebelmouse-image" />
Northwell Health coronavirus testing center at Greater Springfield Community Church.
Credit: Northwell Health<p>Novel coronavirus may spread and infect indiscriminately, but pre-existing conditions, environmental stressors, and a lack of access to care and resources increase the risk of infection. These social determinants make the pandemic more dangerous, and erode communities' and families' abilities to heal from health crises that pre-date the pandemic.</p><p>How do we eliminate these divides? Dr. Salas-Lopez says the first step is recognition. "We have to open our eyes to see the suffering around us," she said. "Northwell has not shied away from that."</p><p>"We are steadfast in improving health outcomes for our vulnerable and underrepresented communities that have suffered because of the prevalence of chronic disease, a problem that led to the disproportionately higher death rate among African-Americans and Latinos during the COVID-19 pandemic," said Michael Dowling, Northwell's president and CEO. "We are committed to using every tool at our disposal—as a provider of health care, employer, purchaser and investor—to combat disparities and ensure the <a href="https://www.northwell.edu/education-and-resources/community-engagement/center-for-equity-of-care" target="_blank" rel="noopener noreferrer">equity of care</a> that everyone deserves." </p><p>With the need recognized, Dr. Salas-Lopez calls for health care systems to travel upstream and be proactive in those hard-hit communities. This requires health care systems to play a strong role, but not a unilateral one. They must build <a href="https://www.northwell.edu/news/insights/faith-based-leaders-are-the-key-to-improving-community-health" target="_blank" rel="noopener noreferrer">partnerships with leaders in those communities</a> and utilize those to ensure relationships last beyond the current crisis. </p><p>"We must meet with community leaders and talk to them to get their perspective on what they believe the community needs are and should be for the future. Together, we can co-create a plan to measurably improve [community] health and also to be ready for whatever comes next," she said.</p><p>Northwell has built relationships with local faith-based and community organizations in underserved communities of color. Those partnerships enabled Northwell to test more than 65,000 people across the metro New York region. The health system also offered education on coronavirus and precautions to curb its spread.</p><p>These initiatives began the process of building trust—trust that Northwell has counted on to return to these communities to administer flu vaccines to prepare for what experts fear may be a difficult flu season.</p><p>While Northwell has begun building bridges across the divides of the New York area, much will still need to be done to cure U.S. health care overall. There is hope that the COVID pandemic will awaken us to the deep disparities in the US.</p><p>"COVID has changed our world. We have to seize this opportunity, this pandemic, this crisis to do better," Dr. Salas-Lopez said. "Provide better care. Provide better health. Be better partners. Be better community citizens. And treat each other with respect and dignity.</p><p>"We need to find ways to unify this country because we're all human beings. We're all created equal, and we believe that health is one of those important rights."</p>
A recent study tested how well the fungi species Cladosporium sphaerospermum blocked cosmic radiation aboard the International Space Station.
- Radiation is one of the biggest threats to astronauts' safety during long-term missions.
- C. sphaerospermum is known to thrive in high-radiation environments through a process called radiosynthesis.
- The results of the study suggest that a thin layer of the fungus could serve as an effective shield against cosmic radiation for astronauts.
Shunk et al.<p>Additionally, the fungus is self-replicating, meaning astronauts would potentially be able to "grow" new radiation shielding on deep-space missions, instead of having to rely on a costly and complicated interplanetary supply chain.</p><p>Still, the researchers weren't sure whether <em>C. sphaerospermum</em> would survive on the space station. Nils J.H. Averesch, a co-author of the <a href="https://www.biorxiv.org/content/10.1101/2020.07.16.205534v1.full.pdf" target="_blank">study published on the preprint server bioRxiv</a>, told <a href="https://www.syfy.com/syfywire/fungus-that-eats-radiation-could-be-cosmic-ray-shield" target="_blank">SYFY WIRE</a>:</p><p style="margin-left: 20px;">"While on Earth, most sources of radiation are gamma- and/or X-rays; radiation in space and on Mars (also known as GCR or galactic cosmic radiation) is of a completely different kind and involves highly energetic particles, mostly protons. This radiation is even more destructive than X- and gamma-rays, so not even survival of the fungus on the ISS was a given."</p>
International Space Station
NASA<p>To be sure, the researchers said more research is needed, and that <em>C. sphaerospermum</em> would likely be used in combination with other radiation-shielding technology aboard spacecraft. But the findings highlight how relatively simple biotechnologies may offer outsized benefits on upcoming space missions.</p><p style="margin-left: 20px;">"Often nature has already developed blindly obvious yet surprisingly effective solutions to engineering and design problems faced as humankind evolves – C. sphaerospermum and melanin could thus prove to be invaluable in providing adequate protection of explorers on future missions to the Moon, Mars and beyond," the researchers wrote.</p>
Shannon Lee shares lessons from her father in her new book, "Be Water, My Friend: The Teachings of Bruce Lee."
- Bruce Lee would have turned 80 years old on November 27, 2020. The legendary actor and martial artist's daughter, Shannon Lee, shares some of his wisdom and his philosophy on self help in a new book titled "Be Water, My Friend: The Teachings of Bruce Lee."
- In this video, Shannon shares a story of the fight that led to her father beginning a deeper philosophical journey, and how that informed his unique expression of martial arts called Jeet Kune Do.
- One lesson passed down from Bruce Lee was his use and placement of physical symbols as a way to help "cement for yourself this new way of being, or this new lesson you've learned." By working on ourselves (with the right tools), we can develop the skills necessary to rise and conquer new challenges.
How to deal with "epistemic exhaustion."