Physicians, medical professionals, clergy-members, and laypeople throughout the world have traditionally accepted that a person is dead when their brain shows no activity. Brain death is defined as the irreversible loss of all functions of the brain, including the brainstem. A person determined to be brain dead is legally and clinically dead. In many of these cases, critically injured or ill persons have been kept alive artificially and their vital functions maintained using mechanical ventilators and other life support technology, even after their brain has ceased to function. But once brain activity has ceased, physicians and families must face the ethical question of removing life support, if used, and allowing the person to die naturally. This is one of the most difficult challenges for a critical care physician and for families.

Even with this belief, many people have held out hope that in the future of scientific discovery, ways to regenerate the brain and body may be found. The practice of cryonics, or low-temperature freezing of a human body after death, has been practiced in the United States since 1967. As of 2014, there have been about 250 people cryopreserved. However, this practice is expensive, costing anywhere from $28,000 to $200,000 (Wikipedia, n.d.).

A recently published study has raised profound questions about life and death, and the line between the two. The study, published in Nature: International Journal of Science, describes the restoration and maintenance of circulation and cellular functions in an intact pig brain up to four hours after death.

Researchers at Yale University acquired the heads of 32 pigs killed for meat. They removed the pig brains and started the experiment. The brains had been without blood and had been at room temperature for four hours. Using an experimental perfusion system called BrainEx, researchers pumped a solution into the intact brains for six hours. The solution brought oxygen to the tissue and contained chemicals that allowed the researchers to track its flow. They were able to observe the preservation of the architecture of brain cells, the attenuation of cell death, and even the restoration of cellular responses, including synaptic activity.

The brains did not regain consciousness, nor were there signs showing coordinated cortical activity (though electrical activity was detected in some neurons), which is necessary for awareness and intelligence. But the blood vessels began functioning and flowed with the blood substitute, and certain brain cells regained metabolic activity for up to 36 hours. The control samples (pig brains that did not receive infusions and those that received placebo substances) showed no signs of activity, and their cells deteriorated. Scientists were careful to say that the responding pig brains were not living brains, but were cellularly active brains.

Though this study is very new and has no immediate implications for the treatment of brain injury, the findings demonstrate that under the appropriate conditions, the brain may have the capacity to be recovered after death. This contradicts everything medical science has believed about the brain and poses several problems. But scientists are hoping that this technology will open the door to new treatments for strokes, traumatic brain injuries, and other neurodegenerative diseases like Alzheimer’s.

The perfusion technology talked about in the pig brain experiments is called “ex vivo” perfusion, and is considered to be far more challenging. The most famous attempt at ex-vivo perfusion was made by Soviet scientist Sergei Brukhonenko, who used a circulation machine to “revive” a decapitated dog. His experiment was documented in the 1940 film “Experiments in the Revival of Organisms.” However, many suspected that the footage was “doctored.”

Bioquark, a Philadelphia-based life science company founded by researcher and CEO Ira Pastor, seeks to find answers in the field of regenerative biology that will one day allow humans to regrow limbs, organs, and brain tissue, much like some animals do. The company’s core focus is finding cures for chronic degenerative diseases of the central nervous system like Alzheimer’s, Parkinson’s, and ALS (amyotrophic lateral sclerosis). One of their current projects, ReAnima, proposes a combination therapy that includes injecting stem cells into the spinal cord of brain dead patients in hopes of reversing it, or bringing the patient back to life. Though the company struggles with regulatory approvals in the United States, they are pursuing clinical trials in India, Mexico, and Albania, where family consent allows researchers to use their experimental therapy on brain dead family members. Bioquark has yet to publish any results or findings.

Why are experiments of brain cell regeneration being conducted? Besides the Soviet experiment on dogs highlighted earlier, was there any precedence in clinical experiments of this nature? A Japanese researcher, Takaaki Kirino, published a groundbreaking paper in 1982 documenting “delayed neuronal death” in Mongolian gerbils. He noted that many of the animals’ brain cells seemed to remain intact long after blood flow had been cut off. Later, the same thing was observed in post-mortem human cerebral tissue. In 1991, scientists discovered that neurons in the brains of lab rats that had been euthanized up to three hours earlier still showed significant electrical activity.

These observations suggested that brain death may not be a single, immediate event, but rather, may happen in gradual steps. And because it may be a gradual process, some scientists believe they may be able to delay or reverse parts of the process. What studies have shown is that the brain may be much more resilient than had been previously thought, that it might be capable of recovering neuronal function, even after being deprived of oxygen for 30 minutes. In other words, it could, essentially, be taken offline and turned back on again. Christof Koch, the president and chief scientist at the Allen Institute for Brain Science, said, “A lot of things about the brain that we once thought were irreversible have turned out not necessarily to be so.”

There have also been anecdotal cases of people who seemed to be dead after prolonged exposure to the cold, who have been resuscitated and their brains continued to function. Others have had a stroke where a clot has blocked blood circulation for up to 16 hours, and have been able to regain brain function once the clots were removed. Perhaps instances like these have inspired researchers to continue to search for answers about the possibility of brain cell regeneration.

Ethically, the idea of brain cell regeneration can pose some daunting ethical questions. Nita A. Farahany, a bioethicist and law professor at Duke University, stated, “We had clear lines between ‘this is alive’ and ‘this is dead,’” and with this research, a new possibility exists that science did not think was possible. Another bioethicist at the University of Pennsylvania, Jonathan Moren, said, “This is wild….if ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one.”

This lesson has been a little different than most in our class. We’ve learned about brain death and what the definition of it is in the medical community. We have also learned that there is a growing field of interest and research in neuronal functioning after death, and that this research holds out hope for finding ways to revive parts of the brain that have experienced brain trauma through stroke, traumatic brain injury, or even neurodegenerative diseases like Alzheimer’s. We have also learned that research, and the many directions it may take in the future, will likely present serious ethical questions about life, death, and reviving people considered medically dead. As Brain Fitness students, it is good to be aware of current research and progress in the field of brain science. The takeaway from all of this could be that there is the future possibility of reviving damaged parts of the brain, and even having hope for loved ones on life support who have lost all brain functions.

Goila, A. K., & Pawar, M. (2009). The diagnosis of brain death. Indian Journal of Critical Care Medicine. Jan-Mar; 13(1): 7-11. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772257/

Kolata, G. (April 17, 2019). ‘Partly alive’: Scientists revive cells in brains from dead pigs. The New York Times. Retrieved from: https://www.nytimes.com/2019/04/17/science/brain-dead-pigs.html?smid=nytcore-ios-share

Muse, Q. (July 24, 2019). Philly-based Bioquark wants a shot at bringing the dead back to life. Philadelphia. Retrieved from: https://www.phillymag.com/healthcare-news/2019/07/25/bioquark-brain-dead-reanima-project-ira-pastor/

Shaer, M. (July 2, 2019). Scientists are giving dead brains new life. What could go wrong? The New York Times Magazine. Retrieved from: https://www.nytimes.com/2019/07/02/magazine/dead-pig-brains-reanimation.html

Vrselja, Z., Daniele, S. G., Silbereis, J. Talpo, F. Morozov, Y. M., Sousa, A. M. M. . . .& Sestan, N. (2019). Restoration of brain circulation and cellular functions hours post-mortem. Nature: International Journal of Science. 568. 336-343. Retrieved from: https://www.nature.com/articles/s41586-019-1099-1

Wikipedia (n.d.). Cryonics. Retrieved from: https://en.wikipedia.org/wiki/Cryonics