Lazarus or Frankenstein?
Is it possible to bring a dead brain back to life?
Ilya Khel, Hi-News
Last month, a Philadelphia-based biotech company launched clinical trials that could revolutionize our understanding of what it means to be dead. After receiving ethical approval from an Independent Ethics Committee, Bioquark dealt with twenty patients at Anupam Hospital in India whose brains were considered clinically dead after severe traumatic brain injury. With an arsenal of cutting–edge, but so far mysterious methods of treatment – stem cells, bioactive molecules, brain and spinal cord stimulation - a group of scientists hopes to resurrect certain parts of the main functions of the patients' brains, with the intention of achieving the best result: to regain the ability to breathe independently.
The results should be known in an extremely short time – 15 days.
If your first reaction was surprise, you're not alone. What is it: the Lazarus effect, Frankenstein, the Walking Dead? Or maybe some kind of viral campaign for an upcoming horror movie?
Not quite. The task of Bioquark is nothing less than to cheat death. This is what they will be doing within the framework of the incredibly ambitious ReAnima project. Let's figure out how it will flow.
This is an amazing word: death
Most often we imagine death in the form of a switch: here you are, and a minute later there is nothing, the light has gone out.
But this is just a caricature of the process of dying: even after the heartbeat and breathing stops, sparks of brain activity can flare up for a long time. In some cases, even deeply comatose patients – unable to breathe on their own – can maintain simple reflex reactions. Their brain waves, erratic or weak, are still being tracked on the EEG.
Brain death, by contrast, is everything, the finish. Such a diagnosis signals the complete and irreversible destruction of the brain, including the brain stem. People with brain dead are not in a coma or in a vegetative state. They have no hope of spontaneous recovery. They're dead.
In many countries around the world, such subjects are classified as "living corpses" (cadavers), says Ira Pastor, CEO of Bioquark (to avoid confusion, this is a man). But this definition has a problem.
In theory, brain death is a very objective and strictly defined medical condition with huge legal consequences. Doctors see brain death in patients as the final signal – it's time to pull the cord, think about organ donation, invite relatives to say goodbye.
In practice, brain death is not so simple at all. The pastor says there is a big "gray area" between a deep coma and brain death. One of the reasons for the "irreversibility" of such a death is dependence on technology. For centuries, the absence of breathing and pulse were signs of death, but the invention of life-sustaining machines and resuscitation methods blurred this line.
Given such a historical precedent, is it possible to talk about the irreversibility of brain death?
Although brain death may seem like some kind of medically savvy definition of death, its criteria were first formed in the late 1960s, long before neurologists dived into serious studies of consciousness and personality. Therefore, brain death does not take into account the latest advances in neurosurgery, the latest technologies and methods, such as measuring the release of neurotransmitters.
The process of diagnosing brain death is very old-fashioned. The doctor can prick the patient with a needle to check the pain receptors, see if carbon dioxide causes spontaneous breathing, try to identify signs of electrical activity in the brain using electroencephalography (EEG). But none of these measures can definitively say that the patient will not return.
Although brain death is based on irreversibility, it is not measurable, says the Pastor. In rare cases, doctors are wrong. Over the past few decades, there have been several dozen cases of spontaneous "resurrection" of brain-dead patients, mostly children and young people. One young woman even successfully gave birth after she was diagnosed with brain death.
"And although these cases are contradictory and are the result of poor diagnosis, we believe that they emphasize the absence of white and black in the field of serious disorders of consciousness," says the Pastor. This is the main incentive for scientists to conduct this niche program.
Lazarus Tools
How to get a brain dead?
The subjects in our study suffer from severe and extensive neuron death, explains Pastor. The integrity of axons–the long projections that neurons use to communicate with each other–is disintegrating and conventional signal processing no longer works.
Alternatively, you can try to save what's left, like repairing broken headphones by tying up the remaining wires. But any attempt to restore a dead brain will probably require spare parts – newly grown brain cells to replace those lost in the process of injury. Moreover, cells need favorable conditions for growth and integration into existing brain circuits.
Bioquark will do both.
The team's "secret sauce" is represented by a combination of bioactive molecules and mesenchymal stem cells (MSC). MSC are available in almost all tissues and have been used in cell replacement therapy for ten years. Although no such trials have been conducted in humans, preliminary studies of rodents with traumatic brain injury have shown that transplanted MSC integrate into the brain and help improve the recovery of motor and cognitive systems.
By studying the extreme stage of brain death, the Pastor and scientists hope to find unique information about the work of the dying brain. There is nothing new in stem cell transplantation, but Bioquark wants to go a step further: armed with bioactive molecules, researchers hope to establish a microenvironment in the brain that will promote "epimorphic regeneration", the process of regrowing the missing part of the body.
When an adult gets physically injured, for example, loses a finger, our body reacts by forming scar tissue. The default response is healing, not regeneration. But during early embryonic development, tissue damage triggers a massive and highly coordinated response that keeps the body from becoming inflamed and scarred. Instead of getting an unpleasant scar, the human fetus can restore the lost tissue, just as flatworms can regenerate severed heads (and perhaps even retain memories from the previous head!).
A large part of this process involves attracting a huge number of local cells that will help the tissue to recover. And not just stem cells. In many cases, adult cells lose their identity and return to the state of stem cells. Thus, the body "recycles" these cells to support tissue regeneration.
This process occurs quite naturally in the fetal body, says the Pastor. Why not take and simulate this process, forcing the adult brain to abandon the scar in favor of regeneration? A previous Bioquark study found that this recovery process depends on bioactive molecules that can be extracted from amphibian eggs.
The extracted bioactive components, mainly microRNAs and proteins, can reprogram damaged cells into the state of stem cells, as the scientists wrote in a 2014 patent. Stem cells are even somewhat minor players. There are fears that their role may be exaggerated, the Pastor believes. They also place more emphasis on morphogenetic extracts. However, relatively few papers have been published on the topic of a leading chemical extract, a mixture of bioactive molecules with the exotic name BQ-A, in animal models of brain death.
The problem is that there are few such models, and they are all far from each other, and some are even exotic, like poisoning pigs with carbon monoxide, explains the Pastor. "We stay away from such models and instead focus on models of traumatic brain injuries and spinal cord injuries in preliminary studies."
First of all, scientists will test the power of these extracts, whether they can reboot the human brain. The pastor emphasizes that the study should show the most basic function of the brain stem after treatment – an electric whisper here, a cloud of neurotransmitter there.
In addition to cell-based therapy, Bioquark also plans to use brain stimulation techniques to enable BQ-A. These methods, including median nerve stimulation and transcranial laser stimulation, are often used to treat coma and other disorders of consciousness with varying degrees of success.
Why use so many different methods? Well, Bioquark wants to know right away what works and what doesn't.
The pastor sees two big drawbacks in modern models of treatment and prevention of the disease. First, they are more focused on treating late-stage symptoms rather than the original cause. Secondly, the approach of reducing any disease to one cause, and as a consequence, to one drug, is often used.
"Epimorphic regeneration by its nature is multifaceted and includes many mechanisms that work in synergy," says Pastor. – To carry out such a complex initiative, it is obviously worth abandoning the concept of a "magic silver bullet" (which will never be) in favor of the concept of a combination."
ReAnimation
"While full recovery is indeed the subject of our long–term vision, it is not the main focus and not the main endpoint of the first study," says the Pastor. The first plan in the schedule will be the resumption of independent breathing. It is unlikely that we will see the awakening of a dead brain in the near future.
But if the treatment works, we may face a thorny philosophical question about personal identity. As bioethicist Dr. Anders Sandberg says, "it is not difficult to imagine that such treatment will not be able to completely restore the brain: memories, personality and functions may be lost, closed or replaced along with the newly grown tissue."
In this case, the treatment will obviously not benefit the person – he will be replaced by someone similar, but different. And yet this is a scenario for the distant future, which may not happen at all. After all, the proposed treatments are experimental, and the regenerative abilities of the brain may be prohibitively limited.
But the Pastor sees value in his endeavors, even if they fail.
"It goes without saying that this is an untouched area of discovery and development. Even if we look into a broader class of "disorders of consciousness," this is an area in which practically no interventional research is taking place," says the Pastor. This is especially evident when considering more "traditional" neurodegenerative disorders, such as Alzheimer's or Parkinson's disease.
"We believe that any of our research in this vein will be invaluable for all these diseases," says the scientist. Lazarus or Frankenstein?
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03.06.2016