Last month, a Philadelphia-based biotech company launched a clinical trial that pushed the meaning of death to its limits.
With Armed Ethics Committee approval from the IRB at Anubang Hospital India, Bioquark is recruiting 20 cases of severe traumatic brain injury who have been clinically considered brain dead.
With an array of cutting-edge, arcane therapeutic techniques—stem cells, bioactive molecules, brain and spinal cord stimulation—the team hopes to restore some basic brain function in patients, ultimately achieving the "Holy Grail" goal of returning to the ability to breathe spontaneously.
Expected deadline for measurable results? Just 15 days.
let it sink in.
If your first reaction is skepticism, you are not alone. What is this, Lazarus Effect , Frankenstein, The Walking Dead ? Some kind of viral promotion for an upcoming horror movie?
is incomplete. A horde of zombies may not be in our future, but Bioquark's goal is to cheat death. That's what the ambitious ReAnima project plans to do.
Defining the thorny problem of death
We often think of death as flipping a switch: one minute you're there, the next minute all the lights are off.
But this is a simple irony of the death process: sparks of brain activity often linger even after heartbeat and breathing stops. In some cases, even deeply coma patients -- unable to breathe on their own -- maintain simple reflex responses. Their brainwaves , no matter how slight or erratic, can still be measured by EEG.
By contrast, brain death is final. Diagnosis indicated complete and irreversible destruction of the brain including brain stem . A brain dead person will not be in a coma or be in a vegetative state.They have no hope of a natural recovery. They are dead. Ira Pastor, CEO of
Bioquark to Singularity Hub, explained that in many countries around the world, these subjects are classified as "living cadavers". But there is a problem with the definition.
In theory, brain death is a highly objective, strictly defined medical condition with enormous legal implications. After all, we think brain-dead patients can't be saved - it's time to pull the plug, consider organ donation, and say our final goodbyes.
But in practice, brain death is not that simple.
Paster says there is a lot of "grey area" between deep coma and brain death. A major reason for
is that "irreversible death" relies heavily on technology. A lack of breathing and a heartbeat has been a hallmark of death for many centuries, but the invention of life-support machines and resuscitation methods has blurred the line.
Given historical precedent, who can say that brain death is truly irreversible?
Although brain death appears to be a medically advanced definition of death, its criteria were first created in the late 1960s, long before neuroscience delved into research consciousness and personality.
Therefore, brain death does not take into account the latest technologies and findings of modern neuroscience, such as measuring the release of the neurotransmitter .
The process of diagnosing brain death is equally old. A doctor may puncture a patient's nail bed to check for pain, see if carbon dioxide triggers spontaneous breathing, and use electroencephalography (EEG) to detect signs of electrical activity in the brain.
However, none of these measures tell us definitively whether it won't make a comeback.
Pastor said that while irreversibility is at the heart of brain death, it is not measurable. In rare cases, the doctor is wrong.Over the past few decades, there have been a handful of dozens of cases of spontaneous rebirth of brain-dead patients, most of whom are children and adolescents. In one particularly incredible case, a young woman gave birth successfully after being diagnosed as brain-dead.
"Despite controversy and resulting poor prognosis, we believe [these] cases highlight that in the realm of severe awareness impairment , things are not always black and white," Pastor said.
He said that was our main motivation for this niche initiative.
Lazarus Kit
How do you quickly start a dead brain?
Pastor explained that the subjects in our study suffered from severe and widespread neuron death. The integrity of the axon—the long projections that neurons use to communicate with each other—disintegrates, and normal signal processing is disrupted.
One workaround is to try to salvage what's left, eg repairing a broken headset by reconfiguring existing wires. However, any attempt by to rebuild dead brains will likely require effective replacement parts - newly grown brain cells to replace brain cells lost through injury. What's more, cells need a favorable environment to help them grow and integrate into existing brain circuits.
Bioquark focuses on both.
The team's "secret recipe" is a combination of bioactive molecules and mesenchymal stem cells (MSCs). MSCs are present in almost all tissues and have been used in cell replacement therapy for nearly 10 years. Although not yet fully tested in human , preliminary studies in rodents with traumatic brain injury suggest that transplanted MSCs integrate into the brain and contribute to enhanced motor and cognitive recovery.
By studying extreme cases of brain damage, Pastor believes the team will gain unique insights into the workings of the dying brain.
Stem cell transplantation is nothing new, but Bioquark wants to go a step further: Using a variety of bioactive molecules, the team hopes to create a microenvironment in the brain that allows for "ectogenesis," the process of regenerating missing body parts.
When an adult suffers a physical injury, such as losing a finger, our body responds by forming scar tissue. The default response is to repair, not regenerate.
However, during early human fetal development, tissue damage triggers a massive and highly coordinated response that steers the body away from inflammation and scarring. Human fetuses don't leave nasty scars, but can rebuild lost tissue, much like the planarian flatworm regenerates severed heads (and possibly retains the memory of the last head!).
Much of this process involves attracting large numbers of local cells to help rebuild the tissue. And they're not just stem cells either. In many cases, mature cells are "dedifferentiated" because they lose their identity and switch back to a stem cell-like state. In this way, the body "recycles" these cells to support tissue regeneration.
Paste said it is a process that occurs naturally in human fetuses. So, we asked - what if we could mimic this process and force the adult brain's default response from repair to regeneration? Previous research by
Bioquark found that this reconstruction process relies on bioactive molecules that can extract from from amphibian egg cells.
The team wrote in a 2014 patent that the extracted bioactive components, mainly microRNA and proteins, can reprogram damaged cells into a stem cell-like state.
In fact, stem cells are somewhat secondary - there are concerns that they may be exaggerated.Our core focus, Pastor explained, is on these morphogenetic extracts.
That said, there are relatively few reports of lead chemical extracts, a mixture of bioactive molecules with the esoteric name BQ-A, in animal models of brain death. The problem with
is that such models are few and far between, and some of them are quite exotic, like poisoning pigs with carbon monoxide, Pastor explained. In our initial study, we eschewed these models and focused instead on traumatic brain injury and spinal cord injury models, he said.
's current trial will be the first to directly test the ability of these extracts to help reboot the human brain.
Pastor emphasized that the study was designed to look at very basic brainstem function after treatment — an electrical whisper here, a burst of neurotransmitters there.
In addition to cell-based therapy, Bioquark plans to supplement BQ-A with brain stimulation technology. These treatments, including median nerve stimulation and transcranial laser stimulation, are commonly used to treat cases of coma and other severe disturbances of consciousness, with varying degrees of success. Why does
use such a large mix of different technologies? Bioquark doesn't want to know right away what works and what doesn't?
Pastor explained that, in my view, the current Big Pharma model of disease intervention has two serious flaws. One is a high focus on treating late symptoms rather than the initial cause. The other is a reductionist approach that attributes any disease to a single cause, and therefore a single drug solution.
"Alien regeneration in nature is multifaceted and involves many mechanisms working together," Pastor said. "There is obviously no 'silver bullet' (and probably never will) for such a complex scheme, hence the concept of a combinatorial agreement."
Resurrection
Paster emphasized that this study was designed to look at very basic brainstem function after treatment - an electrical whisper here, a burst of neurotransmitters there.
"While full recovery ... is indeed our long-term vision ...but it's not the core focus or primary endpoint of the first study," Pastor said. He added that the near-term "holy grail" is restoring spontaneous breathing.
In other words, we won't see the brain fully Awake and alert.
But looking ahead, if treatment works, we may encounter intractable philosophical questions of personal identity. As bioethicist Dr Anders Sandberg considers in The Conversation, “It is not difficult to imagine that this treatment does not The brain is fully restored: memory, personality and function may be disrupted, lost or replaced by new growth. "
In this case the original person would not benefit from the treatment - they would be replaced by a similar but different person.
But that is a distant future that may never happen. After all, the proposed The therapy is highly experimental, and the brain's ability to regenerate - albeit remarkable - can be very limited.
However, even if the trial fails, Pastor sees value in the venture. Discovery and development areas of development. Even if you scan outward into the broader category of 'disorders of consciousness', there is very little research into therapeutic interventions of any kind taking place in this area," Pastor said. This is especially true when compared to Alzheimer's or Parkinson's ).
By studying the extremes of brain injury, Pastor believes the team will gain unique insights into the workings of the dying brain - these The insights could ultimately help in a range of degenerative central nervous system diseases.
"We think 'trickle down' learning is invaluable for all these diseases," he said.
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