Is Alzheimer’s Infectious, and Is a Vaccine Possible?
Dr Arancio is a cellular neurobiologist who has contributed to the characterization of the mechanisms of learning in both normal conditions and during neurodegenerative diseases. During the past decade he has pioneered the field of mechanisms of synaptic dysfunction in Alzheimer’s disease. Dr. Arancio’s laboratory has focused primarily on events triggered by amyloid protein. These studies, which have suggested new links between synaptic dysfunction and amyloid protein, are of a general relevance to the field of Alzheimer’s disease both for understanding the etiopathogenesis of the disease and for developing therapies aiming to improve the cognitive symptoms.
Is Alzheimer’s Infectious, and Is a Vaccine Possible?
Meryl Comer: For the general public the other issue is, is Alzheimer’s infectious? What would...
Dr. Arancio: My take on it is that it might be, but wait a second. It’s not that I'm thinking it’s like a flu and you might get infected. However, we were talking before at tau protein. There is common work and showing that actually it could spread within the brain just like prion disease, the same way, so it starts from one area and then it spreads all over the brain, so it’s not infection in the sense that we understand normal get infected, but it could once it is initiated in a certain part of the brain there is the possibility. It’s not 100% sure, but there are people now we’re starting to see that there is this spreading within the brain, because this tau protein comes out of the cells and spreads to the next cells and then from one area and goes all over the brain and so the disease it’s classical normal... these plaques. They start from a part of the brain and what we call the temporal lobe an then goes from the lobe. At very end it just goes to the occipital lobe, which is where we see, so from this point of view there could, although it has not been totally demonstrated, but there are some people that are following along this path.
Meryl Comer: Dr. Gandy?
Dr. Gandy: I think for classical thoughts about infections I mean like epidemics of flu I would not put Alzheimer’s disease in that category. Back in the 80s a neurologist and scientist and NIH, Carlton Gatacheck and colleague Joe Gibbs tried very, very hard to transmit extracts... use extracts from human Alzheimer’s disease to give the disease to monkeys and they never ever saw any evidence that could be the case.
Meryl Comer: To Dr. Arancio. Dr. Arancio, is a vaccination possible?
Dr. Arancio: All the attempts that are done so far have failed, which does not mean that they will not work in the future. Indeed a very good amount of research in terms of treatment research done on this, on finding a vaccine. Then one thing that we should also know is that there are two kinds of vaccines. One kind of vaccine is what we call "active vaccination," which would be just the same thing that we do with the flu, so you take vaccine and you’re protected for a certain number of years in your life... of your life. In this case one would think about prevention of using vaccine to prevent the disease. There is also what they call passive vaccinations, which will be more short time [...] vaccine. Instead of giving, trying to prompt the body to make what you call the antibodies against the for instance beta amyloid, we give just the antibody that they have a short life. We have to say though that so far all the attempts to fix the problem have failed, but like all the others anyway. That’s what we’re facing, but it could be... it is for sure an interesting avenue to pursue. It would be great if at that time of birth or very short afterward if there were a vaccine, an active vaccination and that will protect us at the very end, but we have to be very careful there too because if for instance what do we vaccinate against? If we vaccinate against A-beta, which is this beta amyloid and if it has some normal function through our life it then could be a negative. We could get also negative effect.
Meryl Comer: For those who know the ravages or have watched the ravages of Alzheimer’s disease in a family, the notion that it might be reversible... Dr. Guarente?
Dr. Guarente: Is it possible?
Meryl Comer: Is it possible?
Dr. Guarente: Well I do get asked that question a lot more broadly about aging: "Is it possible?" And my belief in general is to think that almost anything is possible okay, where science is concerned. Now I do think that at the moment all the research effort is focused on slowing down Alzheimer’s, slowing down aging, slowing down the buildup of and the progression of what is happening in the brain and I think that is the way it has to start because I think we have to be able to do that as a prelude to doing anything more. Now if we can get to effective drugs that can slow the progression of Alzheimer’s and maybe even arrest the deterioration, then I think ultimately, yes, it’s possible. You can imagine replacing neurons that have died by stimulating division of stem cell, neuronal stem cells, and things of that sort, so I think, yes, it’s possible, but I think the way I organize my thoughts on this is first we have to think about the disease and how do we stop it. How do we stop the buildup of damage and how do we arrest it and then we can really... that might give us the space to think about can we actually reverse it and I would give the same kind of answer about aging.
Alzheimer’s starts in one area and spreads all over the brain, like an infection. Does this mean that it's possible to develop a vaccine?
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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.
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