Showing posts with label Science. Show all posts
Showing posts with label Science. Show all posts

April 28, 2018

Immortality? Scientist Keep Brain Cells Alive Outside the Body of An Animal



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Midbrain organoids, measuring about 3 mm across, cultured in the laboratory dish.



Simplified 3D brain organoids can be grown in a dish using human stem cells as the starting material.Credit: Genome Institute of Singapore, A*STAR

If researchers could create brain tissue in the laboratory that might appear to have conscious experiences or subjective phenomenal states, would that tissue deserve any of the protections routinely given to human or animal research subjects? 
This question might seem outlandish. Certainly, today’s experimental models are far from having such capabilities. But various models are now being developed to better understand the human brain, including miniaturized, simplified versions of brain tissue grown in a dish from stem cells — brain organoids1,2. And advances keep being made. 
These models could provide a much more accurate representation of normal and abnormal human brain function and development than animal models can (although animal models will remain useful for many goals). In fact, the promise of brain surrogates is such that abandoning them seems itself unethical, given the vast amount of human suffering caused by neurological and psychiatric disorders, and given that most therapies for these diseases developed in animal models fail to work in people. Yet the closer the proxy gets to a functioning human brain, the more ethically problematic it becomes. 
There is now a need for clear guidelines for research, albeit ones that can be adapted to new discoveries. This is the conclusion of many neuroscientists, stem-cell biologists, ethicists and philosophers — ourselves included — who gathered in the past year to explore the ethical dilemmas raised by brain organoids and related neuroscience tools. A workshop was held in May 2017 at the Duke Initiative for Science & Society at Duke University in Durham, North Carolina, with limited support from the US National Institutes of Health (NIH) BRAIN Initiative. A similar US meeting was held last month on related topics. 
Here we lay out some of the issues that we think researchers, funders, review boards and the public should discuss as a first step to guiding research on brain surrogates. 
Safe surrogates
Three classes of brain surrogate offer researchers a way to investigate how the living human brain works, without the need for potentially risky — if not ethically impossible — procedures in people. 
Organoids. Brain organoids can be produced much as other 3D multicellular structures resembling eye, gut, liver, kidney and other human tissues have been built24. By adding appropriate signaling factors, aggregates of pluripotent stem cells (which have the ability to develop into any cell type) can differentiate and self-organize into structures that resemble certain regions of the human brain57





Investigators use different approaches. They might coax pluripotent stem cells to turn into specific populations of neural cells, such as those specific to a particular brain region. Or they can allow the pluripotent cells to differentiate on their own, in which case both neural cells and other cell types might be generated2. Brain organoids resembling particular brain regions can even be combined into ‘brain assembloids’ to enable researchers to study the formation of neural circuits and cellular interactions between different regions8
Compared with 2D sheets of neural cells in a dish, the 3D structures last longer (for around two years9) and can consist of more types of cell. They also mimic key features of developing brains. For instance, in later stages of fetal development, the cerebral cortex switches from generating neurons to creating glial cells (the various other cell types in the brain that nourish, surround and protect neurons). This process can be captured in brain organoids, allowing investigators to gain insights that would be experimentally and ethically extremely challenging, if not ethically unacceptable, to obtain from developing brains. 
Already, researchers have deployed brain organoids to investigate neurodevelopmental alterations in people with autism spectrum disorders8,10 or schizophrenia11, and to study the unusually small brain size (microcephaly) seen in some babies infected with the Zika virus before birth12
Brain organoids have limitations. They lack certain cell types, such as microglia and cells that form blood vessels. Today, the largest organoids are about 4 millimetres in diameter and contain only about 2 million to 3 million cells. An adult human brain measures roughly 1,350 cubic centimetres, and is made up of 86 billion neurons and a similar number of non-neuronal cells. Moreover, so far, brain organoids have received sensory input only in primitive form, and connections from other brain regions are limited.
Given such constraints, the possibility of organoids becoming conscious to some degree, or of acquiring other higher-order properties, such as the ability to feel distressed, seems highly remote. But organoids are becoming increasingly complex. Indeed, one of us (P.A.) recorded neural activity from an organoid after shining light on a region where cells of the retina had formed together with cells of the brain. This illustrated that an external stimulus can result in an organoid response13.




Slices of human brain for Parkinson's research



A researcher dissects slices of human brain tissue.Credit: Darragh Mason Field/Barcroft Images/Getty

Ex vivo brain tissue. Another type of model involves slices of brain tissue that have been removed from individuals during some surgical procedure, for example to treat seizures. 
For more than a century, researchers have studied brain cells in tissue extracted from patients undergoing surgery, or from people who have died. But technological advances, including in imaging and in the techniques used to preserve the functional properties of brain tissues in the lab (ex vivo), could make this approach considerably more powerful. 
When tissue from the neocortex or hippocampus regions is removed to treat a pathology, such as epilepsy or cancer, the piece removed is typically the size of a sugar cube (about 1–4 cubic centimetres), although it can sometimes be much bigger. That piece is then generally cut into slices, the functional properties of which can be preserved for weeks. 
Using these slices, researchers can measure the synaptic and other properties of neurons in intact brain circuits; map the 3D morphology of circuits; and extract and analyse cellular RNA to probe gene expression. They can also manipulate the firing of specific neurons using optogenetics, which could enable them to analyse in more detail the functional properties of human brain circuits. (Optogenetics uses light to track or selectively activate neurons that have been genetically modified to express a light-sensitive protein.) 
Currently, ex vivo brain tissue does not have sensory inputs. And with outbound connections severed, isolated tissues can’t communicate with other regions of the brain, or generate motor outputs. Thus, the possibility of consciousness or other higher-order perceptive properties emerging seems extremely remote. 
Chimaeras. The third class of experimental brain model involves the transplantation of human cells, derived in vitro from pluripotent stem cells, into the brains of animals such as rodents. This can be done while the animal fetus is developing or after the animal is born. Such chimaeras are generated to provide a more physiologically natural environment in which the human cells can mature. 
Neuroscientists have transplanted human glial cells into mice, for instance, and found that the animals perform better in certain tasks involving learning. Researchers have also injected human stem cells into early-stage pig embryos, and then transferred the embryos into surrogate sows, where they’ve been allowed to develop until the first trimester. More than 150 of the embryos developed into chimaeras; in these embryos, about 1 in 10,000 cells in the precursors of hearts and livers were human. 
In principle, chimaeras could help researchers to better understand human illnesses and the effects of drug treatments. Labs have developed human-mouse chimaeras to shed light on Parkinson’s disease, for example. 
Some groups have even successfully transplanted human brain organoids into rodents, where they have become supported by blood vessels (vascularized)14. The provision of a blood supply is an essential step in enabling organoids to grow larger than their current achievable size. But the size of rodent models restricts the degree to which human brain organoids can grow within them.




Two forebrain organoids that have been assembled



A 3D human-brain assembloid derived from stem cells.Credit: Pasca Lab/Stanford University

Issues to consider
Currently, if research on human tissue occurs outside a living person, only the processes of obtaining, storing, sharing and identifying the tissue fall under the regulations and guidelines that limit what interventions can be conducted on people. As brain surrogates become larger and more sophisticated, the possibility of them having capabilities akin to human sentience might become less remote. Such capacities could include being able to feel (to some degree) pleasure, pain or distress; being able to store and retrieve memories; or perhaps even having some perception of agency or awareness of self. 
Could studies involving brain tissue that has been removed from a living person or corpse provide information about the person’s memories, say? Could organisms that aren’t ‘biologically human’ ever warrant some degree of quasi-human or human moral status? 
In the light of such possibilities, here we lay out some of the issues that we think civil society, researchers, ethicists, funders, and reviewers ought now to be considering. 
Metrics. Is it even possible to assess the sentient capabilities of a brain surrogate? What should researchers measure? If appropriate metrics can be developed, how do investigators decide which capabilities are morally concerning? 
Neuroscientists have made considerable progress when it comes to identifying the neural correlates of consciousness15. Yet the signals for consciousness or unconsciousness detected in a living adult — using electroencephalography (EEG) electrodes, for example — don’t necessarily translate to infants, animals or experimental brain surrogates. Without knowing more about what consciousness is and what building blocks it requires, it might be hard to know what signals to look for in an experimental brain model15
With regard to human–animal chimaeras, researchers are already dealing with beings that have some form of consciousness. Here, the need to establish what measures to base protections on (both for the animal and the human subject) is more pressing. One possibility is for researchers to use anesthetics or other methods to maintain comatose-like brain states. Perhaps certain brain functions or a pre-specified level of brain activity, signaling a lack of capacity, could be used to delineate ethically justifiable research. 
Human-animal blurring. Researchers have already produced mice with rat pancreases by injecting rat pluripotent stem cells into mouse embryos. The same approach could one day enable the production of human organs in other animals16
How do we define the boundaries of this research? What implications might such boundaries have for vascularizing brain organoids, or for growing neural tissue in animals? Is the production of a human heart in a pig’s body acceptable, for instance, but not the production of a brain from human cells?
We believe that decisions about which kinds of chimaera are permitted, or about whether certain human organs grown in animals make animals ‘too human-like’, should ultimately be made on a case-by-case basis — taking into account the risks, benefits and people’s diverse sensitivities. 
Death. Do ex vivo human brain models challenge our understanding of life and death? What implications might such models have for the legal definition of death, and what are the implications for decisions tied to this definition, such as organ donation? 
The advent of tracheal positive-pressure ventilation in the 1950s and cardiopulmonary resuscitation (CPR) in the 1960s led to the concept of brain death. Beginning in the 1960s, a person whose brain had completely and irreversibly ceased to function could be declared dead, even if they still had a heartbeat.
Any emerging technologies that could restore lost functionality to a person’s brain could potentially undermine the diagnosis of brain death, because the cessation of brain function might no longer be permanent and irreversible. But a distinction here is important: technologies that would restore a few neurons or certain limited kinds of brain activity would not restore clinical functionality of the brain and so would not raise this concern.
Consent. Is the standard process of obtaining informed consent adequate for research using human brain cells or tissue, or developing brain surrogates from induced pluripotent stem cells? 
Currently, researchers using pluripotent stem cells or brain tissues generally disclose their plans to donors in broad terms. Given how much people associate their experiences and sense of self with their brains, more transparency and assurances could be warranted. Donors might wish to deny the use of their stem cells for the creation of, say, human-animal chimaeras.
This targeted approach is used in other contexts. When people undergoing in vitro fertilization procedures choose to donate excess embryos to research, for instance, they are assured that these will not be used to create a baby. 
Stewardship. Is there a point at which we should be concerned about the welfare of brain surrogates or chimaeras, such that assigning someone loosely akin to a guardian or decision-maker for the brain surrogate might be warranted, beyond the researchers involved? Such an arrangement would be similar to the appointment of a guardian ad litem in custody disputes involving children in the United States (someone besides the parents who can represent the child’s interests). 
Ownership. Who, if anyone, should ‘own’ ex vivo brain tissue, brain organoids or chimaeras? 
At present, brain tissue samples are owned by the researchers or organizations collecting the tissue or doing the science. If significant developments in the field one day lead us to regard any of these brain surrogates as having greater moral status than we would currently give them, might greater privileges and protections be appropriate?
Post-research handling. How should human brain tissue be disposed of, or handled at the end of an experiment? 
Today, brain organoids or ex vivo brain tissue are destroyed following standard practices for disposing of all tissues. But if researchers develop mice, say, with some advanced cognitive capacities, should those animals be destroyed or given special treatment at the end of a study? Already certain animals, such as chimpanzees, enter sanctuaries to live out the remainder of their lives after researchers have finished working with them in laboratories.
Data. Should there be special requirements for data sharing, collaboration and legacy use of brain tissue? 
The unique benefits and risks of sharing data obtained from such tissues will need to be considered. Ex vivo human brain tissue could reveal sensitive information — for instance, about a person’s memories or disease status. Equally, there could be more value in sharing such information, because of the difficulty of obtaining human brain tissue. In some cases, certain features of the data might need to be stripped out, or the extent of sharing limited. 
Geneticists have long grappled with similar issues for people’s genomic information; some of their approaches could be applied to brain research. 
Ethics efforts
Various efforts are already tackling the ethics of advances in neuroscience17. When the BRAIN Initiative was announced in 2013, the Presidential Commission for the Study of Bioethical Issues was charged with evaluating ethics, and produced a two-volume report in response18,19. The European Commission’s Human Brain Project has a major ethics component, and the NIH BRAIN Initiative has a neuroethics division. 
But we think more needs to be done. Existing institutional ethics review boards or those for stem-cell research oversight might not yet be equipped to address issues specific to these experimental brain models because they are so new. We recommend that such organizations ask experts in this area to join their boards or serve as consultants. New committees, dedicated to overseeing the use of human-brain surrogates, could also be assembled. 
As for the broader societal conversation, various models exist for democratic deliberation that could be applied. One example is the successful consultations between the public, scientists, regulators and bioethicists that preceded the UK government’s decision to permit the clinical use of mitochondrial DNA transfer in 2015. 
As these conversations play out, the major funders of biomedical research should strive to provide guidance and, eventually, guidelines. Also, researchers engaged in the development and use of human-brain surrogates should seek ethical guidance, for instance from their funders, review boards or institutions. They should also share their experiences and concerns, as reviewers, in their own papers or at conferences. 
We do not think that these difficult questions should halt this research. Experimental models of the human brain could help us to unlock mysteries about psychiatric and neurological illnesses that have long remained elusive. But to ensure the success and social acceptance of this research long term, an ethical framework must be forged now, while brain surrogates remain in the early stages of development.


nature.com
Nita A. Farahany, Henry T. Greely and 15 :

March 14, 2018

Steven Hawking and Our Eulogy






To me the death of Steven Hawking is like the death of a star that now becomes part of a black hole and thus it dissapears but we don't know what part it still might play in the universe. If a man can disprove the existence of god, well I was hopping we had him for a few more years. 

He did not have an easy life but he was blessed with a loving wife, three loving offsprings and the opportunity to help the human race in its quest for answers. Thanks goodness that here on earth no one person is indispensable and we do have other scientist minds, many inspired by Steven Hawking himself. Imagined being constrained to a wheel chair and not be able to move but your cheeks and your eyes. But even to that he found an answer.

I wanted to post something on his passing and I read some obits but it was CNN with simple quotes  by him full of wisdom, Iam glad for Steven that at last he is free, just like the day he was born. If there is a god it wont be mad at Steve for proving there is no god because Steven always spoked the truth as he knew it. That is all we can all do. Speak things as we see they are not how we might wish they were or others to see it.
Adam Gonzalez, Publisher Adamfoxie blog


Steve Hawking, A marvolous Scientist with the thirst to know and find out What others didn't or could not
  
 CNN)  "Stephen Hawking was one of the most beloved scientists in this generation -- not only for his intellect, but for his wit and humor."

He died at the age of 76, and left behind provocative as well as comical quotes.

On the universe
"It would not be much of a universe if it wasn't home to the people you love."

On scientific discoveries
"I wouldn't compare it to sex, but it lasts longer." -- at a science festival in 2011.

On persistence
"However difficult life may seem, there is always something you can do and succeed at. It matters that you don't just give up." -- at an Oxford University Union speech in 2016.

On curiosity
"So remember, look at the stars and not at your feet." -- at the Sydney Opera House in 2015.

On intelligence
"I would never claim this. People who boast about their IQ are losers."-- in response to a 2017 question if he believed he was the most intelligent person in the world.

On space
Stephen Hawking Fast Facts
"May you keep flying like superman in microgravity." -- to NASA astronauts in 2014.
"I have always tried to overcome the limitations of my condition and lead as full a life as possible. I have traveled the world, from the Antarctic to zero gravity. Perhaps one day I will go into space." -- to the New York Times in 2011.
"I have already completed a zero gravity flight which allowed me to float weightless, but my ultimate ambition is to fly into space." -- to ITV in 2017.

On God
"God may exist, but science can explain the universe without the need for a creator." -- in a 2010
CNN interview.
"The scientific account is complete. Theology is unnecessary." -- in a 2010 CNN interview.
On women
"My [physician assistant] reminds me that although I have a PhD in physics, women should remain a mystery." -- in his first Reddit AMA. (His PA is a woman, by the way.)
On his appearance
"Unfortunately, Eddie [Redmayne] did not inherit my good looks." -- of the Oscar-winning actor who portrayed him in "The Theory of Everything."


It is adamfoxie's 10th🦊Anniversay. 10 years witnessing the world and bringing you a pieace whcih is ussually not getting its due coverage.

May 2, 2017

Congress on Bipartisan Basis Go Against Trump on Funding Med.Research






 The National Institutes of Health will get a $2 billion funding boost over the next five months, under a bipartisan spending deal reached late Sunday night in Congress. The agreement marks a sharp rejection of President Trump’s proposal to cut $1.2 billion from the medical research agency in the current fiscal year.

The deal does not address funding for 2018, when Trump has called for a slashing the NIH’s budget by about a fifth, or $5.8 billion.

But it sends a clear signal that lawmakers on both sides of the aisle prioritize funding for medical research and intend to honor the agreements laid out in the 21st Century Cures Act, a bipartisan bill that called for raising NIH funding and speeding approvals of new drugs and medical devices. This will be the second year running that Congress gives a $2 billion funding bump to the agency, which funds medical research across the country. 

“The omnibus is in sharp contrast to President Trump’s dangerous plans to steal billions from lifesaving medical research, instead increasing funding for the NIH by $2 billion,” House Minority Leader Nancy Pelosi said in a statement. 
The roughly $1 trillion spending agreement, which funds the government through the end of September, also more than quadruples funds to fight opioid addiction. That money — about $800 million total, up from $150 million in the last budget — will be divided among opioid addiction programs at the Centers for Disease Control and Prevention, the Substance Abuse and Mental Health Services Administration, and the Health Resources and Services Administration.

In addition, the plan permanently extends a health insurance program for coal miners, which had been on the brink of shutting down. It preserves federal funding for Planned Parenthood, for now, though Republicans are still expected to push hard to eliminate that in the 2018 budget.

And in a victory for Democrats, Puerto Rico’s health commissioner announced on her Facebook page that the budget includes $295 million to shore up the territory’s Medicaid program, which should help avert cuts that could have resulted in major coverage losses.

Science isn’t dead in Washington. At least not yet
The NIH funding hike includes an extra $400 million to research Alzheimer’s disease and an additional $476 million for the National Cancer Institute. And it boosts spending on two of former President Barack Obama’s big science projects: the Precision Medicine Initiative, which will get an increase of $120 million as it seeks to recruit volunteers for genetic testing and health tracking; and the BRAIN Initiative, which will get an extra $110 million to support work mapping the human brain.

The spending agreement is a firm repudiation of the Trump administration’s vision of a much leaner federal research program.

Health and Human Services Secretary Tom Price had suggested at a congressional hearing that the NIH budget could be cut significantly without harming medical research by reducing grants for “indirect costs” — the federal dollars that help research universities pay for utility bills, heating costs, pricey equipment, and other expenses that support their biomedical labs. University administrators, who make up a powerful lobbying group, did not take kindly to that suggestion.

 Should taxpayers cover the light bills at university labs? Trump kicks off a tense debate
And from the moment Trump proposed such steep cuts, Republicans have joined Democrats in rejecting them.

The Republican members who chair the health appropriations subcommittees in the House and Senate — Senator Roy Blunt of Missouri and Representative Tom Cole of Oklahoma, respectively — have been steadfast in their support for NIH funding. Senator Lamar Alexander of Tennessee has likewise advocated for research spending, especially as he helped shepherd the 21st Century Cures Act into law.

The agreement lives up to Cole’s word from March, when he told STAT that Trump was unreasonable in requesting a $1.2 billion NIH cut within a budget Congress had largely negotiated before the 2016 presidential election. As he put it then: “Not going to happen.”

By LEV FACHER 

January 23, 2017

Theory Based on Quantum Physics in Which Death Is Not The End

image: http://biocentrismnews.com/wp-content/uploads/sites/23/2016/08/What-HaGraphic image for What Happens When You Die article
This is  theory adamfoxie is sharing with you and is posted by biocentrismnews.com 
It has nothing to do with religious believes but instead on the laws seen as physics and relativity.
                        We watch our loved ones’ age and die and assume that’s the end of the story. We believe in death because we’ve been taught we die. Also, of course, because we associate ourselves with our body and we know bodies die. But biocentrism — a new theory of everything — tells us death may not be the terminal event we think. Amazingly, if you add life and consciousness to the equation, you can explain some of the biggest puzzles of science. For instance, it becomes clear why space and time — and even the properties of matter itself — depend on the observer.
One well-known aspect of quantum physics is that certain observations cannot be predicted absolutely. Instead, there is a range of possible observations each with a different probability. One mainstream explanation, the “many-worlds” interpretation, states that there are an infinite number of universes (the ‘multiverse’). Everything that can possibly happen occurs in some universe. Death doesn’t exist in any real sense in these scenarios since all of them exist simultaneously regardless of what happens in any of them. Although individual bodies are destined to self-destruct, the alive feeling — the ‘Who am I?’— is just a 20-watt fountain of energy operating in the brain. But this energy doesn’t go away at death. One of the surest axioms of science is that energy never dies; it can’t be created or destroyed. But does this energy transcend from one world to the other?
Consider an experiment that was published in in the prestigious scientific journal Science (Jacques et al, 315, 966, 2007). Scientists in France shot photons into an apparatus, and showed that what they did could retroactively change something that had already happened in the past. As the photons passed a fork in the apparatus, they had to decide whether to behave like particles or waves when they hit a beam splitter. Later on — well after the photons passed the fork — the experimenter could randomly switch a second beam splitter on and off. It turns out that what the observer decided at that point, determined what the particle actually did at the fork in the past. Regardless of the choice you, the observer, make, it is you who will experience the outcomes that will result. The linkages between these various histories and universes transcend our ordinary classical ideas of space and time. Think of the 20-watts of energy as simply holo-projecting either this or that result onto a screen. Whether you turn the second beam splitter on or off, it’s still you, the same battery or agent responsible for the projection.
According to Biocentrism, space and time are not the hard cold objects we think. In truth, you can’t see anything through the bone that surrounds your brain. Your eyes are not portals to the world. Everything you see and experience right now — even your body — is a whirl of information occurring in your mind. Wave your hand through the air — if you take everything away, what’s left? Nothing. The same thing applies for time. Space and time are simply the tools for putting everything together.
Death does not exist in a timeless, spaceless world. Einstein knew this. In 1955, when his lifelong friend Michele Besso died, he wrote: “Now he has departed from this strange world a little ahead of me. That means nothing. People like us, who believe in physics, know that the distinction between past, present and future is only a stubbornly persistent illusion.” Immortality doesn’t mean a perpetual existence in time without end, but rather resides outside of time altogether.
This was clear with the death of my sister Christine. After viewing her body at the hospital, I went out to speak with family members. Christine’s husband — Ed — started to sob uncontrollably. For a few moments I felt like I was transcending the provincialism of time. I thought about the 20-watts of energy, and about experiments that show a single particle can pass through two holes at the same time. I could not dismiss the conclusion: Christine was both alive and dead, outside of time.
Christine had had a hard life. She had finally found a man that she loved very much. My younger sister couldn’t make it to her wedding because she had a card game that had been scheduled for several weeks. My mother also couldn’t make the wedding due to an important engagement she had at the Elks Club. The wedding was one of the most important days in Christine’s life. Since no one else from our side of the family showed, Christine asked me to walk her down the aisle to give her away.
Soon after the wedding, Christine and Ed were driving to the dream house they had just bought when their car hit a patch of black ice. She was thrown from the car and landed in a banking of snow.
“Ed,” she said “I can’t feel my leg.”
She never knew that her liver had been ripped in half and blood was rushing into her peritoneum.
After the death of his son, Ralph Waldo Emerson wrote “Our life is not so much threatened as our perception. I grieve that grief can teach me nothing, nor carry me one step into real nature.”
Life is an adventure that transcends our ordinary linear way of thinking. When we die, we do so not in the random billiard-ball-matrix but in the inescapable-life-matrix. Life has a non-linear dimensionality — it’s like a perennial flower that returns to bloom in the multiverse.
Whether it’s flipping the switch for the Science experiment, or turning the driving wheel ever so slightly this way or that way on black-ice, it’s the 20-watts of energy that will experience the result. In some cases the car will swerve off the road, but in other cases the car will continue on its way to my sister’s dream house.
Christine had recently lost 100 pounds, and Ed had bought her a surprise pair of diamond earrings. It’s going to be hard to wait, but I know Christine is going to look fabulous in them the next time I see her.

biocentrismnews.com 

January 21, 2017

When knife Placed on Corpse to Remove Cornea Eyes Flinch, Still Dead?


Reader Advisory-Not for everyone, this is a true medical story. 

 Be educated while your brain works, tell them now how things should be handle or may be you don’t care because you will be dead; But would you really be dead?
The Beating Heart ❥Corpses

Their hearts are still beating. They urinate. Their bodies don’t decompose and they are warm to the touch; their stomachs rumble, their wounds heal and their guts can digest food. They can have heart attacks, catch a fever and suffer from bedsores. They can blush and sweat – they can even have babies.
And yet, according to most legal definitions and the vast majority of doctors these patients are thoroughly, indisputably deceased.
These are the beating heart cadavers; brain-dead corpses with functioning organs and a pulse. Their medical costs are astronomical (up to $217,784 for just a few weeks), but with a bit of luck and a lot of help, today it’s possible for the body to survive for months – or in rare cases, decades – even though it’s technically dead. How is this possible? Why does this happen? And how do doctors know they’re really dead?
Premature burials
Identifying the dead has never been easy. In 19th Century France there were 30 theories about how to tell if someone had passed away – including attaching pincers to their nipples and putting leeches in their bottom. Elsewhere, the most reliable methods included yelling a patient’s name (if the patient ignored them three times, they were dead) or thrusting mirrors under their noses to see if they fogged up.
Suffice to say, the medical establishment wasn’t convinced about any of them. Then in 1846, the Academy of Sciences in Paris launched a competition for “'the best work on the signs of death and the means of preventing premature burials” and a young doctor tried his luck. Eugène Bouchut figured that if a person’s heart had stopped beating, they were surely dead. He suggested using the newly invented stethoscope to listen for a heartbeat – if the doctor didn’t hear anything for two minutes, they could be safely buried.
He won the competition and his definition of “clinical death” stuck, eventually to be immortalised in films, books and popular wisdom. “There wasn’t much that could be done, so basically anyone could look at a person, check for a pulse and decide whether they were dead or alive,” says Robert Veatch from the Kennedy Institute of Ethics.
But a chance discovery in the 1920s made things decidedly messier. An electrical engineer from Brooklyn, New York, had been investigating why people die after they’ve been electrocuted – and wondered if the right voltage might also jolt them back to life. William Kouwenhoven devoted the next 50 years to finding a way to make it happen, work which eventually led to the invention of the defibrillator.
It was the first of a deluge of revolutionary new techniques, including mechanical ventilators and feeding tubes, catheters and dialysis machines. For the first time, you could lack certain bodily functions and still be alive. Our understanding of death was becoming unstuck.
The invention of the EEG – which can be used to identify brain activity – dealt the final blow. Starting in the 1950s, doctors across the globe began discovering that some of their patients, who they had previously considered only comatose, in fact had no brain activity at all. In France the mysterious phenomenon was termed coma dépasse, meaning literally “a state beyond coma”. They had discovered the ‘beating-heart cadavers’, people whose bodies were alive though their brains were dead.
This was an entirely new category of patient, one which overturned 5,000 years of medical understanding in a single sweep, raising new questions about how death is identified and dredging up some thorny philosophical, ethical and legal issues to boot.
 “It goes back and forth as to what people call them but I think patient is the correct term,” says Eelco Wijdicks, a neurologist from Rochester, Minnesota.
These beating heart cadavers should not be confused with other kinds of unconscious patients, such as those in a coma. Though they aren’t able to sit up and respond to the sound of their name, they still show brain activity, undergoing cycles of sleep and (unresponsive) wakefulness. A patient in a coma has the potential to make a full recovery.
A persistent vegetative state is decidedly more serious – in these patients the higher brain is permanently, irretrievably damaged – but though they will never have another conscious thought, again, they are not dead. 
To qualify as a beating heart cadaver, the entire brain must be dead. This includes the “brain stem”, the primitive, tube-shaped mass at the bottom of the brain which controls critical bodily functions, such as breathing. But, somewhat disconcertingly, our other organs aren’t as troubled by the death of their HQ as you’d think.
Alan Shewmon, a neurologist from UCLA and outspoken critic of the brain death definition, identified 175 cases where people’s bodies survived for more than a week after the person had died. In some cases, their hearts kept beating and their organs kept functioning for a further 14 years – for one cadaver, this strange afterlife lasted two decades.
How is this possible?
In fact, biologically speaking, there has never been a single moment of death; each passing is really a series of mini-deaths, with different tissues dropping off at different rates. “Choosing a definition of death is essentially a religious or philosophical question,” says Veatch.
For centuries, soldiers, butchers and executioners have observed how certain body parts may continue twitching after decapitation or dismemberment. Even long before life support, 19th Century physicians related accounts of patients whose hearts had continued to beat for several hours after they stopped breathing.
At times, this slow decline can have alarming consequences. One example is the Lazarus sign, an automatic reflex first reported in 1984. The reflex causes the dead to sit up, briefly raise their arms and drop them, crossed, onto their chests. It happens because while most reflexes are mediated by the brain, some are overseen by “reflex arcs”, which travel through the spine instead. In addition to the Lazarus reflex, corpses also have the knee-jerk reflex intact.
Further along the life-death continuum, skin and brain stem cells are known to remain alive for several days after a person has died. Living muscle stem cells have been found in corpses which are two-and-a-half-weeks old.
Even our genes keep going long after we’ve taken our last breath. Earlier this year, scientists discovered thousands which spring to life days after death, including those involved in inflammation, counteracting stress and – mysteriously – embryonic development.
Beating heart cadavers can only exist because of this lopsided decline – it’s all dependent on the brain dying first. To get to grips with why this happens, consider this. Though the brain makes up just 2% of a person’s body weight, it sucks up a staggering 25% of all its oxygen. 
Neurons are so high-maintenance in part because they are active all the time. They are constantly pumping out ions to create miniature electrical gradients between their insides and the surrounding environment; to fire, they simply open up the floodgates and let the ions flow back in.
The trouble is, they can’t stop pumping. If their efforts are stalled by a lack of oxygen, neurons are rapidly inundated with ions which build to toxic levels, causing irreversible damage. This “ischaemic cascade” explains why if you accidentally lop off a finger, it can usually be sewn back on, but most people can’t hold their breath for more than a few minutes without fainting.
Which brings us back to that perennial medical problem: if your heart’s still beating, how can doctors tell you’re dead? To begin with, doctors identified victims of coma dépasse by checking for the absence of brain activity on an EEG. But there was a problem.
Colleen Burns woke up just as doctors were about to remove her organs 
Alarmingly, alcohol, anaesthesia, some illnesses (such as hypothermia) and many drugs (including Valium) can shut down brain activity, conning doctors into thinking their patient is dead. In 2009, Colleen Burns was found in a drug-induced coma and doctors at a hospital in New York thought she was dead. She woke up in the operating room the day before doctors were due to remove her organs (NB: it’s unlikely this would have gone ahead, because her doctors had planned additional tests before the surgery).
Several decades earlier in 1968, a group of esteemed Harvard doctors called an emergency meeting to discuss exactly this. Over the course of several months, they devised a set of foolproof criteria which would allow doctors to avoid such blunders and establish that beating heart cadavers were definitely dead. 
The tests remain the global standard today, though some of them look uncannily like those from the 19th Century. For a start, a patient should be “unresponsive to verbal stimuli”, such as yelling their name. And though leeches and nipple pincers are out, they should remain unresponsive despite numerous uncomfortable procedures, including injecting ice-cold water into one of their ears – a technique which aims to trigger an automatic reflex and make the eyes move. This particular test is so valuable it won its discoverer a Nobel Prize.
Finally, the patient shouldn’t be able to breathe on their own, since this is a sure sign that their primitive brain is still going. In the case of Burns, the horrifying incident was only possible because her doctors ignored tell-tale signs that she was alive; she curled her toes when they were touched, moved her mouth and tongue and was breathing independently, though she was hooked up to a respirator. Had they followed the Harvard criteria correctly, they would never have declared her dead.
Cadaver donor management
You might expect all medical treatment to stop after someone is considered dead – even if they are a beating heart cadaver – but that’s not quite true. Today beating heart cadavers have spawned a strange new medical specialty, “cadaver donor management”, which aims to improve the success of transplants by tending to the health of the dead. The aim of the game is to fool the body into thinking everything is fine until recipients are lined up and their surgeons are ready.
In all, nearly twice as many viable organs – around 3.9 per cadaver– are retrieved from these donors compared to those without a pulse and they’re currently the only reliable source of hearts for transplant.
Intriguingly, the part of the brain that the body misses most is not its primitive stem or, as we’d like to think, the wrinkled seat of human consciousness (the cortex), but the hypothalamus. The almond-shaped structure monitors levels of important hormones, including those which regulate a person’s blood pressure, appetite, circadian rhythms, sugar levels, fluid balance and energy expenditure – then makes them, or instructs the pituitary gland to do so.
Instead the hormones must be provided by intensive care teams, who add just enough to an intravenous drip as and when they are needed. “It’s not just a case of putting them on a ventilator and giving them some food – it’s far more than that,” says Wijdicks.
Once the consent forms have been signed, dead patients receive the best medical care of their lives 
Of course, not everyone is comfortable with the idea. To some, organ donor management reduces human beings to mere collections of organs to be stripped for parts. As journalist Dick Teresi cynically put it, once the consent forms have been signed, dead patients receive the best medical care of their lives.
These interventions are only possible because the Harvard tests promise to sort the dead and the living into neat boxes – but alas, yet again death is messier than we’d like to think. In a review of 611 patients diagnosed as brain dead using their criteria, scientists found brain activity in 23%. In another study, 4% had sleep-like patterns of activity for up to a week after they had died. Others have reported beating heart cadavers flinching under the surgeon’s knife and there have even been suggestions that they should be given an anaesthetic – though this is controversial.
To inject further controversy into the mix, some people don’t even agree with the definition in principle, let alone in practice. In the United States, many Orthodox Jews, some Roman Catholics and certain ethnic minorities – in total, around 20% of the population – like their dead with a flat-lining heart rate and cold to the touch. “There’s this group of people who quite militantly are offended when a doctor tries to pronounce death on someone that the family thinks are still alive,” says Veatch.
“Even with clinical death, there are disputes – for instance about how long it’s necessary for circulation to be lost before it’s impossible for it to be restored. We use five minutes in the US but there isn’t really good evidence that that’s the right number,” says Veatch.
At the heart of many legal struggles is the right to choose your own definition of death and when life support should be removed, issues Veatch is particularly passionate about. “I have consistently supported individuals who would insist on a circulatory definition, though that’s not the one I would use,” he says.
Where it gets particularly sticky is if the victim is pregnant. In these cases, the patient’s family have a heart-breaking choice to make. They can either accept that they’ve lost her unborn baby, or begin the intensive and often gruesome battle to keep her going long enough to deliver, which is usually when the foetus is about 24-weeks-old.
Back in 2013, Marlise Munoz was found unconscious at her home in Texas. Her doctors suspected that she had suffered a pulmonary embolism and discovered that she was 14 weeks pregnant. Two days later she was declared dead. Munoz was a paramedic and had previously told her husband that in case of brain death, she would not want to be kept alive artificially. He petitioned to have her life support removed – but the hospital refused.
“In Texas there’s an automatic invalidation of a pregnant woman’s advanced directive. If she wanted them to withdraw life-sustaining treatment, then when she died that would not be allowed – that would be ripped up. She would be provided life-sustaining treatment,” says Christopher Burkle, an anaesthetist from Rochester, Minnesota who co-authored a paper on the subject with Wijdicks.
The circumstances are extremely rare, with only about 30 reported cases between 1982 and 2010, but the tug-of-war between the interests of the mother and those of her unborn baby begs the question: which human rights should we retain when we’re dead?
“In the US a dead patient still has rights to the protection of their medical information, for example. You can’t publish their medical record on the 6 o’clock news – a person who is dead has privacy rights in that respect. It’s not a huge jump to suggest that rights be maintained in other avenues for a dead person,” says Burkle.
And things may be about to get a lot more complicated. At the moment, doctors are bound by the “dead donor rule”, which asserts that no organs can be removed until a person is dead – that is, totally brain-dead or with a heart which has already stopped beating. But some people, including Veatch, think this should change.
They have proposed the “higher brain” definition, which means a person isn’t dead when their heart stops beating, or even when they stop breathing – a person is dead when they lose their “personhood”. Those with crucial parts of their brains intact and the ability to breathe independently would be dead so long as they could no longer have conscious thoughts. 
By loosening up the definition a little further, transplant doctors would have access to a much larger pool of potential donors than they do at the moment and save countless lives.
Death isn’t an event, it’s a process – but after thousands of years of trying, we’re still searching for something more definitive. It doesn’t look like this is about to end any time soon.
 --By Zaria Gorvett
  From BBC Future, Earth, Culture.

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