A Door Into Summer
Cooper Campbell, Robert C.W. Ettinger, Benjamin Franklin, Neil R. Jones, Mathew Shaer
1773, 1931, 1962, 2017-2019
CRT monitors, digital media player, digital to analog signal converters, digital video splitter.
1 Hour, 26 Minutes, 11 Seconds
Presented in four channel digital video
Four texts are displayed on four separate CRT teleprompters: A letter, A New Use for Madeira Wine by Benjamin Franklin (1773); a story, The Jameson Satellite by Neil R. Jones (1931); an essay, The Problem of Identity, excepted from The Prospect of Immortality by Robert C.W. Ettinger (1962); and an article, Scientists Are Giving Dead Brains New Life. What Could Go Wrong? by Mathew Shaer (2019).
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[2 min]
A New Use for Madeira Wine
Benjamin Franklin, April 1773
To: Jacques Barbeu Dubourg
Your observations on the causes of death, and the experiments which you propose for recalling to life those who appear to be killed by lightning, demonstrates equally your sagacity and your humanity. It appears that the doctrine of life and death in general is yet but little understood.
A toad buried in the sand may live, it is said, until the sand becomes petrified; and then, being enclosed in stone, it may still live for we know not how many centuries. The facts which are cited in support of this opinion are too numerous, and too circumstantial not to deserve a certain degree of credit.
I have seen an instance of common flies preserved in a manner somewhat similar. They had been drowned in Madeira wine, apparently about the time when it was bottled in Virginia, to be sent here [to London]. At the opening of one of the bottles, at the house of a friend where I was, three drowned flies fell into the first glass that we filled. Having heard it remarked that drowned flies come back to life in the sun, I proposed making the experiment upon these. They were therefore exposed to the sun upon a sieve which was employed to strain them out of the wine.
In less than three hours, two of them began by degrees to recover life. They commenced by some convulsive motions in the thighs, and at length they raised themselves upon their legs, wiped their eyes with their forefeet, beat and brushed their wings with their hind feet, and soon after flew away, finding themselves in Old England, without knowing how they came thither.
The third continued lifeless till sunset, when, losing all hopes of him, he was thrown away. I wish it were possible, from this instance, to invent a method of embalming drowned persons, in such a manner that they might be recalled to life by the solar warmth of my dear country. But since, in all probability, we live in a century too little advanced, and too near the infancy of science, to see such an art brought in our time to its perfection, I must, for the present, content myself with the treat, which you are so kind as to promise me, of the resurrection of a fowl or turkey cock.
I am, etc. B. Franklin
Cooper Campbell, Robert C.W. Ettinger, Benjamin Franklin, Neil R. Jones, Mathew Shaer
1773, 1931, 1962, 2017-2019
CRT monitors, digital media player, digital to analog signal converters, digital video splitter.
1 Hour, 26 Minutes, 11 Seconds
Presented in four channel digital video
Four texts are displayed on four separate CRT teleprompters: A letter, A New Use for Madeira Wine by Benjamin Franklin (1773); a story, The Jameson Satellite by Neil R. Jones (1931); an essay, The Problem of Identity, excepted from The Prospect of Immortality by Robert C.W. Ettinger (1962); and an article, Scientists Are Giving Dead Brains New Life. What Could Go Wrong? by Mathew Shaer (2019).
[2 min]A New Use for Madeira Wine
Benjamin Franklin, April 1773
To: Jacques Barbeu Dubourg
Your observations on the causes of death, and the experiments which you propose for recalling to life those who appear to be killed by lightning, demonstrates equally your sagacity and your humanity. It appears that the doctrine of life and death in general is yet but little understood.
A toad buried in the sand may live, it is said, until the sand becomes petrified; and then, being enclosed in stone, it may still live for we know not how many centuries. The facts which are cited in support of this opinion are too numerous, and too circumstantial not to deserve a certain degree of credit.
I have seen an instance of common flies preserved in a manner somewhat similar. They had been drowned in Madeira wine, apparently about the time when it was bottled in Virginia, to be sent here [to London]. At the opening of one of the bottles, at the house of a friend where I was, three drowned flies fell into the first glass that we filled. Having heard it remarked that drowned flies come back to life in the sun, I proposed making the experiment upon these. They were therefore exposed to the sun upon a sieve which was employed to strain them out of the wine.
In less than three hours, two of them began by degrees to recover life. They commenced by some convulsive motions in the thighs, and at length they raised themselves upon their legs, wiped their eyes with their forefeet, beat and brushed their wings with their hind feet, and soon after flew away, finding themselves in Old England, without knowing how they came thither.
The third continued lifeless till sunset, when, losing all hopes of him, he was thrown away. I wish it were possible, from this instance, to invent a method of embalming drowned persons, in such a manner that they might be recalled to life by the solar warmth of my dear country. But since, in all probability, we live in a century too little advanced, and too near the infancy of science, to see such an art brought in our time to its perfection, I must, for the present, content myself with the treat, which you are so kind as to promise me, of the resurrection of a fowl or turkey cock.
I am, etc. B. Franklin
[44 min]
The Jameson Satellite
Neil R. Jones, 1931
The mammoths of the ancient world have been wonderfully preserve in the ice of Siberia. The cold, only a few miles out in space, will be far more intense than in the polar regions and its power of preserving the dead body would most probably be correspondingly increased. When the hero-scientist of this story knew he must die, he conceived a brilliant idea for the preservation of his body, the result of which even exceeded his expectations. What, how, and why are cleverly told here.
Prologue: The Rocket Satellite
In the depths of space, some twenty thousand miles from the earth, the body of Professor Jameson within its rocket container cruised upon an endless journey, circling the gigantic sphere. The rocket was a satellite of the huge, revolving world around which it held to its orbit. In the year 1958, Professor Jameson had sought for a plan whereby he might preserve his body indefinitely after his death. He had worked long and hard upon the subject.
Since the time of the Pharaohs, the human race had looked for a means by which the dead might be preserved against the ravages of time. Great had been the art of the Egyptians in the embalming of their deceased, a practice which was later lost to humanity of the ensuing mechanical age, never to be rediscovered. But even the embalming of the Egyptians—so Professor Jameson had argued--would be futile in the face of millions of years, the dissolution of the corpses being just as eventual as immediate cremation following death.
The professor had looked for a means by which the body could be preserved perfectly forever. But eventually he had come to the conclusion that nothing on earth is unchangeable beyond a certain limit of time. Just as long as he sought an earthly means of preservation, he was doomed to disappointment. All earthly elements are composed of atoms which are forever breaking down and building up, but never destroying themselves. A match may be burned, but the atoms are still unchanged, having resolved themselves into smoke, carbon dioxide, ashes, and certain basic elements. It was clear to the professor that he could never accomplish his purpose if he were to employ one system of atomic structure, such as embalming fluid or other concoction, to preserve another system of atomic structure, such as the human body, when all atomic structure is subject to universal change, no matter how slow.
[Illustration: It glowed in a haze of light, the interior clearly revealed.]
He had then soliloquized upon the possibility of preserving the human body in its state of death until the end of all earthly time--to that day when the earth would return to the sun from which it had sprung. Quite suddenly one day he had conceived the answer to the puzzling problem which obsessed his mind, leaving him awed with its wild, uncanny potentialities.
He would have his body shot into space enclosed in a rocket to become a satellite of the earth as long as the earth continued to exist. He reasoned logically. Any material substance, whether of organic or inorganic origin, cast into the depths of space would exist indefinitely. He had visualized his dead body enclosed in a rocket flying off into the illimitable maw of space. He would remain in perfect preservation, while on earth millions of generations of mankind would live and die, their bodies to molder into the dust of the forgotten past. He would exist in this unchanged manner until that day when mankind, beneath a cooling sun, should fade out forever in the chill, thin atmosphere of a dying world. And still his body would remain intact and as perfect in its rocket container as on that day of the far-gone past when it had left the earth to be hurled out on its career. What a magnificent idea!
At first he had been assailed with doubts. Suppose his funeral rocket landed upon some other planet or, drawn by the pull of the great sun, were thrown into the flaming folds of the incandescent sphere? Then the rocket might continue on out of the solar system, plunging through the endless seas of space for millions of years, to finally enter the solar system of some far-off star, as meteors often enter ours. Suppose his rocket crashed upon a planet, or the star itself, or became a captive satellite of some celestial body?
It had been at this juncture that the idea of his rocket becoming the satellite of the earth had presented itself, and he had immediately incorporated it into his scheme. The professor had figured out the amount of radium necessary to carry the rocket far enough away from the earth so that it would not turn around and crash, and still be not so far away but what the earth's gravitational attraction would keep it from leaving the vicinity of the earth and the solar system. Like the moon, it would forever revolve around the earth.
He had chosen an orbit sixty-five thousand miles from the earth for his rocket to follow. The only fears he had entertained concerned the huge meteors which careened through space at tremendous rates of speed. He had overcome this obstacle, however, and had eliminated the possibilities of a collision with these stellar juggernauts. In the rocket were installed radium repulsion rays which swerved all approaching meteors from the path of the rocket as they entered the vicinity of the space wanderer.
The aged professor had prepared for every contingency, and had set down to rest from his labors, reveling in the stupendous, unparalleled results he would obtain. Never would his body undergo decay; and never would his bones bleach to return to the dust of the earth from which all men originally came and to which they must return. His body would remain millions of years in a perfectly preserved state, untouched by the hoary palm of such time as only geologists and astronomers can conceive.
His efforts would surpass even the wildest dreams of H. Rider Haggard, who depicted the wondrous, embalming practices of the ancient nation of Kor in his immortal novel, "She," wherein Holly, under the escort of the incomparable Ayesha, looked upon the magnificent, lifelike masterpieces of embalming by the long-gone peoples of Kor.
With the able assistance of a nephew, who carried out his instructions and wishes following his death, Professor Jameson was sent upon his pilgrimage into space within the rocket he himself had built. The nephew and heir kept the secret forever locked in his heart.
* * * * *
Generation after generation had passed upon its way. Gradually humanity had come to die out, finally disappearing from the earth altogether. Mankind was later replaced by various other forms of life which dominated the globe for their allotted spaces of time before they too became extinct. The years piled up on one another, running into millions, and still the Jameson Satellite kept its lonely vigil around the earth, gradually closing the distance between satellite and planet, yielding reluctantly to the latter's powerful attraction.
Forty million years later, its orbit ranged some twenty thousand miles from the earth while the dead world edged ever nearer the cooling sun whose dull, red ball covered a large expanse of the sky. Surrounding the flaming sphere, many of the stars could be perceived through the earth's thin, rarefied atmosphere. As the earth cut in slowly and gradually toward the solar luminary, so was the moon revolving ever nearer the earth, appearing like a great gem glowing in the twilight sky.
The rocket containing the remains of Professor Jameson continued its endless travel around the great ball of the earth whose rotation had now ceased entirely--one side forever facing the dying sun. There it pursued its lonely way, a cosmic coffin, accompanied by its funeral cortege of scintillating stars amid the deep silence of the eternal space which enshrouded it. Solitary it remained, except for the occasional passing of a meteor flitting by at a remarkable speed on its aimless journey through the vacuum between the far-flung worlds.
Would the satellite follow its orbit to the world's end, or would its supply of radium soon exhaust itself after so many eons of time, converting the rocket into the prey of the first large meteor which chanced that way? Would it some day return to the earth as its nearer approach portended, and increase its acceleration in a long arc to crash upon the surface of the dead planet? And when the rocket terminated its career, would the body of Professor Jameson be found perfectly preserved or merely a crumbled mound of dust?
Chapter I: 40,000,000 Years After
Entering within the boundaries of the solar system, a long, dark, pointed craft sped across the realms of space towards the tiny point of light which marked the dull red ball of the dying sun which would some day lie cold and dark forever. Like a huge meteor it flashed into the solar system from another chain of planets far out in the illimitable Universe of stars and worlds, heading towards the great red sun at an inconceivable speed.
Within the interior of the space traveler, queer creatures of metal labored at the controls of the space flyer which juggernauted on its way towards the far-off solar luminary. Rapidly it crossed the orbits of Neptune and Uranus and headed sunward. The bodies of these queer creatures were square blocks of a metal closely resembling steel, while for appendages, the metal cube was upheld by four jointed legs capable of movement. A set of six tentacles, all metal, like the rest of the body, curved outward from the upper half of the cubic body. Surmounting it was a queer-shaped head rising to a peak in the center and equipped with a circle of eyes all the way around the head. The creatures, with their mechanical eyes equipped with metal shutters, could see in all directions. A single eye pointed directly upward, being situated in the space of the peaked head, resting in a slight depression of the cranium.
These were the Zoromes of the planet Zor which rotated on its way around a star millions of light years distant from our solar system. The Zoromes, several hundred thousand years before, had reached a stage in science, where they searched for immortality and eternal relief from bodily ills and various deficiencies of flesh and blood anatomy. They had sought freedom from death, and had found it, but at the same time they had destroyed the propensities for birth. And for several hundred thousand years there had been no births and few deaths in the history of the Zoromes.
This strange race of people had built their own mechanical bodies, and by operation upon one another had removed their brains to the metal heads from which they directed the functions and movements of their inorganic anatomies. There had been no deaths due to worn-out bodies. When one part of the mechanical men wore out, it was replaced by a new part, and so the Zoromes continued living their immortal lives which saw few casualties. It was true that, since the innovation of the machines, there had been a few accidents which had seen the destruction of the metal heads with their brains. These were irreparable. Such cases had been few, however, and the population of Zor had decreased but little. The machine men of Zor had no use for atmosphere, and had it not been for the terrible coldness of space, could have just as well existed in the ether void as upon some planet. Their metal bodies, especially their metal-encased brains, did require a certain amount of heat even though they were able to exist comfortably in temperatures which would instantly have frozen to death a flesh-and-blood creature.
The most popular pastime among the machine men of Zor was the exploration of the Universe. This afforded them a never ending source of interest in the discovery of the variegated inhabitants and conditions of the various planets on which they came to rest. Hundreds of space ships were sent out in all directions, many of them being upon their expeditions for hundreds of years before they returned once more to the home planet of far-off Zor.
This particular space craft of the Zoromes had entered the solar system whose planets were gradually circling in closer to the dull red ball of the declining sun. Several of the machine men of the space craft's crew, which numbered some fifty individuals, were examining the various planets of this particular planetary system carefully through telescopes possessing immense power.
These machine men had no names and were indexed according to letters and numbers. They conversed by means of thought impulses, and were neither capable of making a sound vocally nor of hearing one uttered.
"Where shall we go?" queried one of the men at the controls questioning another who stood by his side examining a chart on the wall.
"They all appear to be dead worlds, 4R-3579," replied the one addressed, "but the second planet from the sun appears to have an atmosphere which might sustain a few living creatures, and the third planet may also prove interesting for it has a satellite. We shall examine the inner planets first of all, and explore the outer ones later if we decide it is worth the time."
"Too much trouble for nothing," ventured 9G-721. "This system of planets offers us little but what we have seen many times before in our travels. The sun is so cooled that it cannot sustain the more common life on its planets, the type of life forms we usually find in our travels. We should have visited a planetary system with a brighter sun."
"You speak of common life," remarked 25X-987. "What of the uncommon life? Have we not found life existent on cold, dead planets with no sunlight and atmosphere at all?"
"Yes, we have," admitted 9G-721, "but such occasions are exceedingly rare."
"The possibility exists, however, even in this case," reminded 4R-3579, "and what if we do spend a bit of unprofitable time in this one planetary system--haven't we all an endless lifetime before us? Eternity is ours."
"We shall visit the second planet first of all," directed 25X-987, who was in charge of this particular expedition of the Zoromes, "and on the way there we shall cruise along near the third planet to see what we can of the surface. We may be able to tell whether or not it holds anything of interest to us. If it does, after visiting the second planet, we shall then return to the third. The first world is not worth bothering with."
* * * * *
The space ship from Zor raced on in a direction which would take it several thousand miles above the earth and then on to the planet which we know as Venus. As the space ship rapidly neared the earth, it slackened its speed, so that the Zoromes might examine it closely with their glasses as the ship passed the third planet.
Suddenly, one of the machine men ran excitedly into the room where 25X-987 stood watching the topography of the world beneath him.
"We have found something!" he exclaimed.
"What?"
"Another space ship!"
"Where?"
"But a short distance ahead of us on our course. Come into the foreport of the ship and you can pick it up with the glass."
"Which is the way it's going?" asked 25X-987.
"It is behaving queerly," replied the machine man of Zor. "It appears to be in the act of circling the planet."
"Do you suppose that there really is life on that dead world--intelligent beings like ourselves, and that this is one of their space craft?"
"Perhaps it is another exploration craft like our own from some other world," was the suggestion.
"But not of ours," said 25X-987.
Together, the two Zoromes now hastened into the observation room of the space ship where more of the machine men were excitedly examining the mysterious space craft, their thought impulses flying thick and fast like bodiless bullets.
"It is very small!"
"Its speed is slow!"
"The craft can hold but few men," observed one.
"We do not yet know of what size the creatures are," reminded another. "Perhaps there are thousands of them in that space craft out there. They may be of such a small size that it will be necessary to look twice before finding one of them. Such beings are not unknown."
"We shall soon overtake it and see."
"I wonder if they have seen us?"
"Where do you suppose it came from?"
"From the world beneath us," was the suggestion.
“Perhaps."
Chapter II: The Mysterious Space Craft
The machine men made way for their leader, 25X-987, who regarded the space craft ahead of them critically.
"Have you tried communicating with it yet?" he asked.
"There is no reply to any of our signals," came the answer.
"Come alongside of it then," ordered their commander. "It is small enough to be brought inside our carrying compartment, and we can see with our penetration rays just what manner of creatures it holds. They are intelligent, that is certain, for their space ship does imply as much."
The space flyer of the Zoromes slowed up as it approached the mysterious wanderer of the cosmic void which hovered in the vicinity of the dying world.
"What a queer shape it has," remarked 25X-987. "It is even smaller than I had previously calculated."
A rare occurrence had taken place among the machine men of Zor. They were overcome by a great curiosity which they could not allow to remain unsatiated. Accustomed as they were to witnessing strange sights and still stranger creatures, meeting up with weird adventures in various corners of the Universe, they had now become hardened to the usual run of experiences which they were in the habit of encountering. It took a great deal to arouse their unperturbed attitudes. Something new, however, about this queer space craft had gripped their imaginations, and perhaps a subconscious influence asserted to their minds that here they have come across an adventure radically unusual.
"Come alongside it," repeated 25X-987 to the operator as he returned to the control room and gazed through the side of the space ship in the direction of the smaller cosmic wanderer.
"I'm trying to," replied the machine man, "but it seems to jump away a bit every time I get within a certain distance of it. Our ship seems to jump backward a bit too."
"Are they trying to elude us?"
"I don't know. They should pick up more speed if that is their object."
"Perhaps they are now progressing at their maximum speed and cannot increase their acceleration any more."
"Look!" exclaimed the operator. "Did you just see that? The thing has jumped away from us again!"
"Our ship moved also," said 25X-987. "I saw a flash of light shoot from the side of the other craft as it jumped."
Another machine man now entered and spoke to the commander of the Zorome expedition.
"They are using radium repellent rays to keep us from approaching," he informed.
"Counteract it," instructed 25X-987.
The man left, and now the machine man at the controls of the craft tried again to close with the mysterious wanderer of the space between planets. The effort was successful, and this time there was no glow of repulsion rays from the side of the long metal cylinder.
They now entered the compartment where various objects were transferred from out the depths of space to the interplanetary craft. Then patiently they waited for the rest of the machine men to open the side of their space ship and bring in the queer, elongated cylinder.
"Put it under the penetration ray!" ordered 25X-987. "Then we shall see what it contains!"
The entire group of Zoromes were assembled about the long cylinder, whose low nickel-plated sides shone brilliantly. With interest they regarded the fifteen-foot object which tapered a bit towards its base. The nose was pointed like a bullet. Eight cylindrical protuberances were affixed to the base while the four sides were equipped with fins such as are seen on aerial bombs to guide them in a direct, unswerving line through the atmosphere. At the base of the strange craft there projected a lever, while in one side was a door which, apparently opened outward. One of the machine men reached forward to open it but was halted by the admonition of the commander.
"Do not open it up yet!" he warned. "We are not aware of what it contains!"
Guided by the hand of one of the machine men, a series of lights shone down upon the cylinder. It became enveloped in a haze of light which rendered the metal sides of the mysterious space craft dim and indistinct while the interior of the cylinder was as clearly revealed as if there had been no covering. The machine men, expecting to see at least several, perhaps many, strange creatures moving about within the metal cylinder, stared aghast at the sight they beheld. There was but one creature, and he was lying perfectly still, either in a state of suspended animation or else of death. He was about twice the height of the mechanical men of Zor. For a long time they gazed at him in a silence of thought, and then their leader instructed them.
"Take him out of the container."
The penetration rays were turned off, and two of the machine men stepped eagerly forward and opened the door. One of them peered within at the recumbent body of the weird-looking individual with the four appendages. The creature lay up against a luxuriously upholstered interior, a strap affixed to his chin while four more straps held both the upper and lower appendages securely to the insides of the cylinder. The machine man released these, and with the help of his comrade removed the body of the creature from the cosmic coffin in which they had found it.
"He is dead!" pronounced one of the machine men after a long and careful examination of the corpse. "He has been like this for a long time."
"There are strange thought impressions left upon his mind," remarked another.
One of the machine men, whose metal body was of a different shade than that of his companions, stepped forward, his cubic body bent over that of the strange, cold creature who was garbed in fantastic accoutrements. He examined the dead organism a moment, and then he turned to his companions.
"Would you like to hear his story?" he asked.
"Yes!" came the concerted reply.
"You shall, then," was the ultimatum. "Bring him into my laboratory. I shall remove his brain and stimulate the cells into activity once more. We shall give him life again, transplanting his brain into the head of one of our machines."
With these words he directed two of the Zoromes to carry the corpse into the laboratory.
As the space ship cruised about in the vicinity of this third planet which 25X-987 had decided to visit on finding the metal cylinder with its queer inhabitant, 8B-52, the experimenter, worked unceasingly in his laboratory to revive the long-dead brain cells to action once more. Finally, after consummating his desires and having his efforts crowned with success, he placed the brain within the head of a machine. The brain was brought to consciousness. The creature's body was discarded after the all-important brain had been removed.
Chapter III: Recalled to Life
As Professor Jameson came to, he became aware of a strange feeling. He was sick. The doctors had not expected him to live; they had frankly told him so--but he had cared little in view of the long, happy years stretched out behind him. Perhaps he was not to die yet. He wondered how long he had slept. How strange he felt--as if he had no body. Why couldn't he open his eyes? He tried very hard. A mist swam before him. His eyes had been open all the time but he had not seen before. That was queer, he ruminated. All was silent about his bedside. Had all the doctors and nurses left him to sleep--or to die?
Devil take that mist which now swam before him, obscuring everything in line of vision. He would call his nephew. Vainly he attempted to shout the word "Douglas," but to no avail. Where was his mouth? It seemed as if he had none. Was it all delirium? The strange silence--perhaps he had lost his sense of hearing along with his ability to speak--and he could see nothing distinctly. The mist had transferred itself into a confused jumble of indistinct objects, some of which moved about before him.
He was now conscious of some impulse in his mind which kept questioning him as to how he felt. He was conscious of other strange ideas which seemed to be impressed upon his brain, but this one thought concerning his indisposition clamored insistently over the lesser ideas. It even seemed just as if someone was addressing him, and impulsively he attempted to utter a sound and tell them how queer he felt. It seemed as if speech had been taken from him. He could not talk, no matter how hard he tried. It was no use. Strange to say, however, the impulse within his mind appeared to be satisfied with the effort, and it now put another question to him. Where was he from? What a strange question--when he was at home. He told them as much. Had he always lived there? Why, yes, of course.
The aged professor was now becoming more astute as to his condition. At first it was only a mild, passive wonderment at his helplessness and the strange thoughts which raced through his mind. Now he attempted to arouse himself from the lethargy.
Quite suddenly his sight cleared, and what a surprise! He could see all the way around him without moving his head! And he could look at the ceiling of his room! His room? Was it his room! No-- It just couldn’t be. Where was he? What were those queer machines before him? They moved on four legs. Six tentacles curled outward from their cubical bodies. One of the machines stood close before him. A tentacle shot out from the object and rubbed his head. How strange it felt upon his brow. Instinctively he obeyed the impulse to shove the contraption of metal from him with his hands.
His arms did not rise, instead six tentacles projected upward to force back the machine. Professor Jameson gasped mentally in surprise as he gazed at the result of his urge to push the strange, unearthly looking machine-caricature from him. With trepidation he looked down at his own body to see where the tentacles had come from, and his surprise turned to sheer fright and amazement. His body was like the moving machine which stood before him! Where was he? What ever had happened to him so suddenly? Only a few moments ago he had been in his bed, with the doctors and his nephew bending over him, expecting him to die. The last words he had remembered hearing was the cryptic announcement of one of the doctors.
"He is going now."
But he hadn't died after all, apparently. A horrible thought struck him! Was this the life after death? Or was it an illusion of the mind? He became aware that the machine in front of him was attempting to communicate something to him. How could it, thought the professor, when he had no mouth. The desire to communicate an idea to him became more insistent. The suggestion of the machine man's question was in his mind. Telepathy, thought he.
The creature was asking about the place whence he had come. He didn’t know; his mind was in such a turmoil of thoughts and conflicting ideas. He allowed himself to be led to a window where the machine with waving tentacle pointed towards an object outside. It was a queer sensation to be walking on the four metal legs. He looked from the window and he saw that which caused him to nearly drop over, so astounded was he.
The professor found himself gazing out from the boundless depths of space across the cosmic void to where a huge planet lay quiet. Now he was sure it was an illusion which made his mind and sight behave so queerly. He was troubled by a very strange dream. Carefully he examined the topography of the gigantic globe which rested off in the distance. At the same time he could see back of him the concourse of mechanical creatures crowding up behind him, and he was aware of a telepathic conversation which was being carried on behind him--or just before him. Which was it now? Eyes extended all the way around his head, while there existed no difference on any of the four sides of his cubed body. His mechanical legs were capable of moving in any of four given directions with perfect ease, he discovered.
The planet was not the earth--of that he was sure. None of the familiar continents lay before his eyes. And then he saw the great dull red ball of the dying sun. That was not the sun of his earth. It had been a great deal more brilliant.
"Did you come from that planet?" came the thought impulse from the mechanism by his side.
"No," he returned.
He then allowed the machine men--for he assumed that they were machine men, and he reasoned that, somehow or other they had by some marvelous transformation made him over just as they were--to lead him through the craft of which he now took notice for the first time. It was an interplanetary flyer, or space ship, he firmly believed.
25X-987 now took him to the compartment which they had removed him to from the strange container they had found wandering in the vicinity of the nearby world. There they showed him the long cylinder.
"It's my rocket satellite!" exclaimed Professor Jameson to himself, though in reality every one of the machine men received his thoughts plainly. "What is it doing here?"
"We found your dead body within it," answered 25X-987. "Your brain was removed to the machine after having been stimulated into activity once more. Your carcass was thrown away."
Professor Jameson just stood dumfounded by the words of the machine man.
"So I did die!" exclaimed the professor. "And my body was placed within the rocket to remain in everlasting preservation until the end of all earthly time! Success! I have now attained unrivaled success!” He then turned to the machine man. "How long have I been that way?" he asked excitedly.
"How should we know?" replied the Zorome. "We picked up your rocket only a short time ago, which, according to your computation, would be less than a day. This is our first visit to your planetary system and we chanced upon your rocket. So it is a satellite? We didn't watch it long enough to discover whether or not it was a satellite. At first we thought it to be another traveling space craft, but when it refused to answer our signals we investigated."
"And so that was the earth at which I looked," mused the professor. “No wonder I didn't recognize it. The topography has changed so much. How different the sun appears--it must have been over a million years ago when I died!"
"Many millions," corrected 25X-987. "Suns of such size as this one do not cool in so short a time as you suggest."
Professor Jameson, in spite of all his amazing computations before his death, was staggered by the reality.
"Who are you?" he suddenly asked.
"We are the Zoromes from Zor, a planet of a sun far across the Universe."
25X-987 then went on to tell Professor Jameson something about how the Zoromes had attained their high stage of development and had instantly put a stop to all birth, evolution and death of their people, by becoming machine men.
Chapter IV: The Dying World
"And now tell us of yourself," said 25X-987, "and about your world."
Professor Jameson, noted in college as a lecturer of no mean ability and perfectly capable of relating intelligently to them the story of the earth's history, evolution and march of events following the birth of civilization up until the time when he died, began his story. The mental speech hampered him for a time, but he soon became accustomed to it so as to use it easily, and he found it preferable to vocal speech after a while. The Zoromes listened interestedly to the long account until Professor Jameson had finished.
"My nephew," concluded the professor, "evidently obeyed my instructions and placed my body in the rocket I had built, shooting it out into space where I became the satellite of the earth for these many millions of years."
"Do you really want to know how long you were dead before we found you?” asked 25X-987. "It would be interesting to find out."
"Yes, I should like very much to know," replied the professor.
"Our greatest mathematician, 459C-79, will tell it to you." The mathematician stepped forward. Upon one side of his cube were many buttons arranged in long columns and squares.
"What is your unit of measuring?" he asked.
"A mile."
"How many times more is a mile than is the length of your rocket satellite?”
"My rocket is fifteen feet long. A mile is five thousand two hundred and eighty feet."
The mathematician depressed a few buttons.
"How far, or how many miles from the sun was your planet at that time?"
"Ninety-three million miles," was the reply.
"And your world's satellite--which you call moon from your planet--earth?"
"Two hundred and forty thousand miles."
"And your rocket?"
"I figured it to go about sixty-five thousand miles from the earth."
"It was only twenty thousand miles from the earth when we picked it up,” said the mathematician, depressing a few more buttons. "The moon and sun are also much nearer your planet now."
* * * * *
Professor Jameson gave way to a mental ejaculation of amazement.
"Do you know how long you have cruised around the planet in your own satellite?" said the mathematician. "Since you began that journey, the planet which you call the earth has revolved around the sun over forty million times."
"Forty--million--years!" exclaimed Professor Jameson haltingly. "Humanity must then have all perished from the earth long ago! I'm the last man on earth!"
"It is a dead world now," interjected 25X-987.
"Of course," elucidated the mathematician, "those last few million years are much shorter than the ones in which you lived. The earth's orbit is of less diameter and its speed of revolution is greatly increased, due to its proximity to the cooling sun. I should say that your year was some four times as long as the time in which it now takes your old planet to circumnavigate the sun.
"How many days were there in your year?"
"Three hundred and sixty-five."
"The planet has now ceased rotating entirely."
"Seems queer that your rocket satellite should avoid the meteors so long," observed 459C-79, the mathematician.
"Automatic radium repulsion rays," explained the professor.
"The very rays which kept us from approaching your rocket," stated 25X-987, "until we neutralized them."
"You died and were shot out into space long before any life occurred on Zor," soliloquized one of the machine men. "Our people had not yet even been born when yours had probably disappeared entirely from the face of the earth."
"Hearken to 72N-4783," said 25X-987, "he is our philosopher, and he just loves to dwell on the past life of Zor when we were flesh and blood creatures with the threat of death hanging always over our heads. At that time, like the life you knew, we were born, we lived and died, all within a very short time, comparatively."
"Of course, time has come to mean nothing to us, especially when we are out in space," observed 72N-4783. "We never keep track of it on our expeditions, though back in Zor such accounts are accurately kept. By the way, do you know how long we stood here while you recounted to us the history of your planet? Our machine bodies never get tired, you know."
* * * * *
"Well," ruminated Professor Jameson, giving a generous allowance of time. "I should say about a half a day, although it seemed scarcely as long as that."
"We listened to you for four days," replied 72N-4783.
Professor Jameson was really aghast.
"Really, I hadn't meant to be such a bore," he apologized.
"That is nothing," replied the other. "Your story was interesting, and if it had been twice as long, it would not have mattered, nor would it have seemed any longer. Time is merely relative, and in space actual time does not exist at all, any more than your forty million years’ cessation of life seemed more than a few moments to you. We saw that it was so when your first thought impressions reached us following your revival."
"Let us continue on to your planet earth," then said 25X-987. “Perhaps we shall find more startling disclosures there."
As the space ship of the Zoromes approached the sphere from which Professor Jameson had been hurled in his rocket forty million years before, the professor was wondering how the earth would appear, and what radical changes he would find. Already he knew that the geographical conditions of the various continents were changed. He had seen as much from the space ship.
A short time later the earth was reached. The space travelers from Zor, as well as Professor Jameson, emerged from the cosmic flyer to walk upon the surface of the planet. The earth had ceased rotating, leaving one-half its surface always toward the sun. This side of the earth was heated to a considerable degree, while its antipodes, turned always away from the solar luminary, was a cold, frigid, desolate waste. The space travelers from Zor did not dare to advance very far into either hemisphere, but landed on the narrow, thousand-mile strip of territory separating the earth's frozen half from its sun-baked antipodes.
As Professor Jameson emerged from the space ship with 25X-987, he stared in awe at the great transformation four hundred thousand centuries had wrought. The earth's surface, its sky and the sun were all so changed and unearthly appearing. Off to the east the blood red ball of the slowly cooling sun rested upon the horizon, lighting up the eternal day. The earth's rotation had ceased entirely, and it hung motionless in the sky as it revolved around its solar parent, its orbit slowly but surely cutting in toward the great body of the sun. The two inner planets, Mercury and Venus, were now very close to the blood red orb whose scintillating, dazzling brilliance had been lost in its cooling process. Soon, the two nearer planets would succumb to the great pull of the solar luminary and return to the flaming folds, from which they had been hurled out as gaseous bodies in the dim, age-old past, when their careers had just begun.
The atmosphere was nearly gone, so rarefied had it become, and through it Professor Jameson could view with amazing clarity without discomfort to his eyes the bloated body of the dying sun. It appeared many times the size he had seen it at the time of his death, on account of its relative nearness. The earth had advanced a great deal closer to the great star around which it swung.
The sky towards the west was pitch black except for the iridescent twinkle of the fiery stars which studded that section of the heavens. As he watched, a faint glow suffused the western sky, gradually growing brighter, the full moon majestically lifted itself above the horizon, casting its pale, ethereal radiance upon the dying world beneath. It was increased to many times the size Professor Jameson had ever seen it during his natural lifetime. The earth's greater attraction was drawing upon the moon just as the sun was pulling the earth ever nearer itself.
This cheerless landscape confronting the professor represented the state of existence to which the earth had come. It was a magnificent spread of loneliness which bore no witness to the fact that it had seen the teeming of life in better ages long ago. The weird, yet beautiful scene, spread in a melancholy panorama before his eyes, drove his thoughts into gloomy abstraction with its dismal, depressing influence. Its funereal, oppressive aspect smote him suddenly with the chill of a terrible loneliness.
25X-987 aroused Professor Jameson from his lethargic reverie. "Let us walk around and see what we can find. I can understand how you feel in regard to the past. It is quite a shock--but it must happen to all worlds sooner or later--even to Zor. When that time comes, the Zoromes will find a new planet on which to live. If you travel with us, you will become accustomed to the sight of seeing dead, lifeless worlds as well as new and beautiful ones pulsating with life and energy. Of course, this world being your own, holds a peculiar sentimental value to you, but it is really one planet among billions."
Professor Jameson was silent.
"I wonder whether or not there are any ruins here to be found?" queried 25X-987.
"I don't believe so," replied the professor. "I remember hearing an eminent scientist of my day state that, given fifty thousand years, every structure and other creation of man would be obliterated entirely from off the earth's surface."
"And he was right," endorsed the machine man of Zor. "Time is a great effacer."
For a long time the machine men wandered over the dreary surface of the earth, and then 25X-987 suggested a change of territory to explore. In the space ship, they moved around the earth to the other side, still keeping to the belt of shadowland which completely encircled the globe like some gigantic ring. Where they now landed arose a series of cones with hollow peaks.
"Volcanoes!" exclaimed the professor.
"Extinct ones," added the machine man.
Leaving the space ship, the fifty or more machine men, including also Professor Jameson, were soon exploring the curiously shaped peaks. The professor, in his wanderings had strayed away from the rest, and now advanced into one of the cup-like depressions of the peak, out of sight of his companions, the Zoromes.
Chapter V: Eternity or Death
He was well in the center of the cavity when the soft ground beneath him gave way suddenly and he catapulted below into the darkness. Through the Stygian gloom he fell in what seemed to be an endless drop. He finally crashed upon something hard. The thin crust of the volcano's mouth had broken through, precipitating him into the deep, hollow interior.
It must have been a long ways to fall--or so it had seemed. Why was he not knocked senseless or killed? Then he felt himself over with three tentacles. His metal legs were four broken, twisted masses of metal, while the lower half of his cubic body was jammed out of shape and split. He could not move, and half of his six tentacles were paralyzed.
How would he ever get out of there? he wondered. The machine men of Zor might never find him. What would happen to him, then? He would remain in this deathless, monotonous state forever in the black hole of the volcano's interior unable to move. What a horrible thought! He could not starve to death; eating was unknown among the Zoromes, the machines requiring no food. He could not even commit suicide. The only way for him to die would be to smash the strong metal head, and in his present immovable condition, this was impossible.
It suddenly occurred to him to radiate thoughts for help. Would the Zoromes receive his messages? He wondered how far the telepathic messages would carry. He concentrated the powers of his mind upon the call for help, and repeatedly stated his position and plight. He then left his mind clear to receive the thought answers of the Zoromes. He received none. Again he tried. Still he received no welcoming answer. Professor Jameson became dejected.
* * * * *
It was hopeless. The telepathic messages had not reached the machine men of Zor. They were too far away, just as one person may be out of earshot of another's voice. He was doomed to a terrible fate of existence! It were better that his rocket had never been found. He wished that the Zoromes had destroyed him instead of bringing him back to life--back to this!
His thoughts were suddenly broken in upon.
"We're coming!"
"Don't give up hope!"
If the professor's machine body had been equipped with a heart, it would have sung for joy at these welcome thought impressions. A short time later there appeared in the ragged break of the volcano's mouth, where he had fallen through, the metal head of one of the machine men.
"We shall have you out of there soon," he said.
* * * * *
The professor never knew how they managed it for he lost consciousness under some strange ray of light they projected down upon him in his prison. When he came to consciousness once more, it was to find himself inside the space ship.
"If you had fallen and had smashed your head, it would have been all over with you," were the first thought impulses which greeted him. “As it is, however, we can fix you up first rate."
"Why didn't you answer the first time I called to you?" asked the professor. "Didn't you hear me?"
"We heard you, and we answered, but you didn't hear us. You see, your brain is different than ours, and though you can send thought waves as far as we can you cannot receive them from such a great distance."
"I'm wrecked," said the professor, gazing at his twisted limbs, paralyzed tentacles and jammed body.
"We shall repair you," came the reply. "It is your good fortune that your head was not crushed."
"What are you going to do with me?" queried the professor. "Will you remove my brains to another machine?"
"No, it isn't necessary. We shall merely remove your head and place it upon another machine body."
The Zoromes immediately set to work upon the task, and soon had Professor Jameson's metal head removed from the machine which he had wrecked in his fall down the crater. All during the painless operation, the professor kept up a series of thought exchanges in conversation with the Zoromes, and it seemed but a short time before his head surmounted a new machine and he was ready for further exploration. In the course of his operation, the space ship had moved to a new position, and now as they emerged 25X-987 kept company with Professor Jameson.
"I must keep an eye on you," he said. "You will be getting into more trouble before you get accustomed to the metal bodies."
But Professor Jameson was doing a great deal of thinking. Doubtlessly, these strange machine men who had picked up his rocket in the depths of space and had brought him back to life, were expecting him to travel with them and become adopted into the ranks of the Zoromes. Did he want to go with them? He couldn't decide. He had forgotten that the machine men could read his innermost thoughts.
"You wish to remain here alone upon the earth?" asked 25X-987. "It is your privilege if you really want it so."
"I don't know," replied Professor Jameson truthfully.
* * * * *
He gazed at the dust around his feet. It had probably been the composition of men, and had changed from time to time into various other atomic structures--of other queer forms of life which had succeeded mankind. It was the law of the atom which never died. And now he had within his power perpetual existence. He could be immortal if he wished! It would be an immortality of never-ending adventures in the vast, endless Universe among the galaxy of stars and planets.
A great loneliness seized him. Would he be happy among these machine men of another far-off world--among these Zoromes? They were kindly and solicitous of his welfare. What better fate could he expect? Still, a longing for his own kind arose in him--the call of humanity. It was irresistible. What could he do? Was it not in vain? Humanity had long since disappeared from the earth--millions of years ago. He wondered what lay beyond the pales of death--the real death, where the body decomposed and wasted away to return to the dust of the earth and assume new atomic structures.
He had begun to wonder whether or not he had been dead all these forty millions of years--suppose he had been merely in a state of suspended animation. He had remembered a scientist of his day, who had claimed that the body does not die at the point of official death. According to the claims of this man, the cells of the body did not die at the moment at which respiration, heart beats and the blood circulation ceased, but it existed in the semblance of life for several days afterward, especially in the cells of the bones, which died last of all.
Perhaps when he had been sent out into space in his rocket right after his death, the action of the cosmic void was to halt his slow death of the cells in his body, and hold him in suspended animation during the ensuing millions of years. Suppose he should really die--destroying his own brain? What lay beyond real death? Would it be a better plane of existence than the Zoromes could offer him? Would he rediscover humanity, or had they long since arisen to higher planes of existence or reincarnation? Did time exist beyond the mysterious portals of death? If not, then it was possible for him to join the souls of the human race. Had he really been dead all this time? If so, he knew what to expect in case he really destroyed his own brain. Oblivion!
Again the intense feeling of loneliness surged over him and held him within its melancholy grasp. Desperately, he decided to find the nearest cliff and jump from it--head-first! Humanity called; no man lived to companion him. His four metal limbs carried him swiftly to the summit of a nearby precipice. Why not gamble on the hereafter? 25X-987, understanding his trend of thought, did not attempt to restrain him. Instead, the machine man of Zor waited patiently.
As Professor Jameson stood there meditating upon the jump which would hurl him now into a new plane of existence--or into oblivion, the thought transference of 25X-987 reached him. It was laden with the wisdom born of many planets and thousands of centuries' experience.
"Why jump?" asked the machine man. "The dying world holds your imagination within a morbid clutch. It is all a matter of mental condition. Free your mind of this fascinating influence and come with us to visit other worlds, many of them are both beautiful and new. You will then feel a great difference.
"Will you come?"
The professor considered for a moment as he resisted the impulse to dive off the declivity to the enticing rocks far below. An inspiration seized him. Backing away from the edge of the cliff, he joined 25X-987 once more.
"I shall come," he stated.
He would become an immortal after all and join the Zoromes in their never-ending adventures from world to world. They hastened to the space ship to escape the depressing, dreary influence of the dying world, which had nearly driven Professor Jameson to take the fatal leap to oblivion.
THE END
[22 Min]The Prospect of Immortality, The Problem of Identity
Robert C.W. Ettinger, 1962
In considering the chances of reviving, curing, rejuvenating, and improving a frozen man, we have to envisage the possibility of some very extensive repairs and alteration. This leads to a number of very perplexing puzzles.
As an extreme case, imagine an elderly cancer victim who is not frozen until several hours after death, and then only by crude methods. Almost all the cells of his body have suffered severe damage and are thoroughly dead by present criteria, although some would grow in culture and we assume a small percentage of them have degenerated relatively little. But after enough centuries pass medical art at last is ready to deal with him, and for the sake of emphasis let us assume a grotesque mixture of techniques is used.
When our resuscitee emerges from the hospital he may be a crazy quilt of patchwork. His internal organs - heart, lungs, liver, kidneys, stomach, and all the rest - may be grafts, implanted after being grown in the laboratory from someone else's donor cells. His arms and legs may be bloodless artifacts of fabric, metal and plastic, directed by his own will and complete with sense of touch but extended and flexed by tiny motors. His brain cells may be mostly new, regenerated from the few which could be saved, and some of his memories and personality traits may have had to be imprinted on or into the new cells by microtechniques of chemistry and physics, after being ascertained from the written records.
Striding eagerly into the new world, he feels like a new man. Is he?
Who is this resuscitee? For that matter, who am I and who are you?
Although most resuscitees will not represent such extreme cases - we hope most of us will be frozen by non-damaging methods - nevertheless we cannot sidestep the issue. We are now face to face with one of the principal unsolved problems of philosophy and/or biology, which now becomes one of prime importance in an exceedingly practical way, namely that concerning the nature of "self."
What characterizes an individual? What is the soul, or essence, or ego? This seemingly abstruse question will shortly be seen to have ramifications in almost every area of practical affairs; it will be the subject of countless newspaper editorials and Congressional investigations, and will reach the Supreme Court of the United States.
We can bring the problem into better focus by putting it in the form of two questions. First, how can we distinguish one man from another? Second, how can we distinguish life from death?
Later I shall offer some tentative partial answers. First we can illuminate the question, and perceive some of its difficulties and subtleties, by considering a series of experiments. Some of these experiments are imaginary, but perhaps not impossible in principle, while others have actually been performed.
Experiment 1.
We allow a man to grow older
Legally, he retains his identity; and also subjectively, and also in the minds of his acquaintances (usually). Yet most of the material of his body is replaced and changed; his memories change, and some are lost; his outlook and personality change.
It is even possible that an old acquaintance, seeing him again after many years, might refuse to believe he is the same person. On first considering this experiment, we are apt to feel slightly disturbed, but to retain a vague conviction that "basically" the man is unchanged. We may feel that the physical and psychological continuity has some bearing on the question.
Experiment 2.
We watch a sudden, drastic change in a man's personality and physique, brought about by physical damage, or disease, or emotional shock, or some combination of these. Such has often occurred.
Afterwards, there may be little resemblance to the previous man, mentally or physically. There may be "total" amnesia, although he may recover capability of speech.
Of course he retains, e.g., the same fingerprints, and the same genes. But it would be absurd to say the main part of a man is his skin; and identical twins have the same genes, yet are separate individuals.
Although the physical material of his body is the same stuff, he seems - and feels - like a different person. Now we are more seriously disturbed, because the main continuity is merely physical; there is a fairly sharp discontinuity in personality. One might say with some plausibility that a man was destroyed, and another man was created, inheriting the tissues of his predecessor's body.
Experiment 3.
We observe an extreme case of "split personality."
It is commonly believed that sometimes two (or even more) disparate personalities seem to occupy the same body, sometimes one exercising control and sometimes the other. Partly separate sets of memories may be involved. The two "persons" in the same body may dislike each other; they may be able to communicate only by writing notes when dominant, for the other to read when his turn comes.
We may be inclined to dismiss this phenomenon by talking about psychosis or pathology. This tendency is reinforced by the fact that apparently one of the personalities is usually eventually submerged, or the two are integrated, leaving us with the impression that "really" there was only one person all along. Nevertheless, the personalities may for a time seem completely distinct by behavioral tests, and subjectively the difference is obviously real. This may leave us with a disturbing impression that possibly the essence of individuality lies after all in the personality, in the pattern of the brain's activity, and in its memory.
Experiment 4.
Applying biochemical or microsurgical techniques to a newly fertilized human ovum, we force it to divide and separate, thereby producing identical twins where the undisturbed cell would have developed as a single individual. (Similar experiments have been performed, with animals.)
An ordinary individual should probably be said to originate at the moment of conception. At any rate, there does not seem to be any other suitable time - certainly not the time of birth, because a Caesarean operation would have produced a living individual as well; and choice of any other stage of development of the fetus would be quite arbitrary.
Our brief, coarse, physical interference has resulted in two lives, two individuals, where before there was one. In a sense, we have created one life. Or perhaps we have destroyed one life, and created two, since neither individual is quite the same as the original one would have been.
Although it does not by any means constitute proof, the fact that a mere, crude, mechanical or chemical manipulation can "create a soul" suggests that such portentous terms as "soul" and "individuality" may represent nothing more than clumsy attempts to abstract from, or even inject into, a system certain "qualities" which have only a limited relation to physical reality.
Experiment 5.
By super-surgical techniques (which may not be far in the future) we lift the brains from the skulls of two men, and interchange them.
This experiment might seem trivial to some. Most of us, after thinking it over, will agree it is the brain which is important, and not the arms, nor the legs, nor even the face. If Joe puts on a mask resembling Jim, he is still Joe; and even if the "mask" is of living flesh and extends to the whole body, our conclusion will probably be the same. The assemblage of Joe's brain in Jim's body will probably be identified as Joe. But at least two factors make this experiment non-trivial.
First, if the experiment were actually performed and not merely discussed, the emotional impact on the parties concerned would be powerful. The wives would be severely shaken, as would the subjects. Furthermore, Joe-in-Jim’s-body would rapidly change, since personality depends heavily on environment, and the body is an important part of the brain's environment. Also, we may be willing to admit that Joe's arms, legs, face, and intestines are not essential attributes of Joe - but what about his testicles? If Joe-in-Jim’s-body lies with one of their wives, he can only beget Jim's child, since he is using Jim's gonads. The psychiatric and legal problems involved here are formidable indeed.
Some people might be tempted to give up on Joe and Jim altogether, and start afresh with Harry and Henry. In one sense, this is an impractical evasion, since the memories, family rights and property rights cannot be dismissed. From another view, it may be a sensible admission that characterization of an individual is to some extent arbitrary.
Once again, the suggestion is that physical systems (i.e., real systems) must in the end be described by physical parameters (operationally) and that attempts to pin profound or abstract labels on them, or to categorize them in subjective terms, cannot be completely successful.
Experiment 6.
By super-surgical techniques (not yet available) we divide a man's brain in two, separating the left and right halves, and transplant one half into another skull (whose owner has been evicted).
Similar, but less drastic, experiments have been performed. Working with split-brain monkeys, Dr. C. B. Trevarthen has reported that " . . . the surgically separated brain halves may learn side by side at the normal rate, as if they were quite independent." (121) This is most intriguing, even though the brains were not split all the way down to the brain stem, and even though monkeys are not men.
There is also other evidence in the literature which we can summarize, with certain simplifications and exaggerations, as follows. Either half of a brain can take over an individual's functions independently. Normally, one half dominates, and loss of the other half is not too serious. But even if the dominant half is removed, or killed, the other half will take over, learning the needed skills.
There is presently no conclusive evidence that so drastic an experiment as ours would necessarily succeed; but in principle, as far as I know, it might, and we are not at the moment concerned with technical difficulties.
If it did succeed, we would have created a new individual. If the left half was dominant, we might label the original individual LR; the same skull containing the left half alone after surgery we might call L, and the right half alone, in a different skull after the operation, is R. L thinks of himself as being the same as LR. R may also think of himself as LR, recuperated after a sickness, but to the outside world he may seem to be a new and different, although similar, person.
In any case, R is now an individual in his own right, and regards his life to be as precious as anyone else's. He will cling to life with the usual tenacity, and if he sees death approaching will probably not be consoled by the knowledge that L lives on.
Even more interesting is the attitude of L, the formerly dominant half, now alone in the skull. Suppose that, before the operation, we had told LR that the dominant half of his brain was diseased, and would have to be removed, but that the other half would take over, albeit with some personality changes and possibly some loss of memory. He would be worried and disturbed, certainly -- but he would probably not regard this as a death sentence. In other words, LR would be consoled well enough by the assurance that R would live on. Yet after the splitting, and transplanting operation, L would regard his own destruction as death, and it would not satisfy him that R lived on, in another body.
This experiment seems to suggest again that, psychologically if not logically, the physical continuity is an important consideration.
Experiment 7.
A man is resuscitated after a short period of clinical death, with some loss of memory and some change in personality.
This experiment has actually been performed many times. Death was real by the usual clinical tests (no respiration, no heartbeat) but of course most of the cells remained alive, and most people would say that he had not "really" died, and that he was certainly the same person afterward. This experiment is important only as background for the following ones.
Experiment 8.
A man dies, and lies unattended for a couple of days, passing through biological death and cellular death. But now a marvel occurs; a space ship arrives from a planet of the star Arcturus, carrying a supersurgeon of an elder race, who applies his arts and cures the man of death and decay, as well as his lesser ailments.
(It is not, of course, suggested that any such elder race exists; the experiment is purely hypothetical, but as far as we know today it is not impossible in principle.)
The implications are apt to shake us. If decay is to be regarded as just another disease, with a possibility of cure, then when may the body be considered truly dead? If "truly" dead be taken to mean "permanently" dead, then we may never know when we are in the presence of death, since the criterion is not what has already happened to the man, but what is going to happen to him in the (endless?) future.
Experiment 9.
A man dies, and decays, and his components are scattered. But after a long time a super-being somehow collects his atoms and reassembles them, and the man is recreated.
Once more, the difficulty or even impossibility of the experiment is not important. We also disregard the question of the possibility of identifying individual elementary particles. Is it the "same" man, in spite of the sharp physical discontinuity in time? If memory, personality, and physical substance are all the same, perhaps most of us would think so, even though we are disturbed by the black gulf of death intervening. But if we so admit, we must open the door even wider.
Experiment 10.
We repeat the previous experiment, but with a less faithful reproduction, involving perhaps only some of the original atoms and only a moderately good copy. Is it still the same man?
Again, perhaps, we wonder if there is really any such thing as an individual in any clear-cut and fundamental sense.
Experiment 11.
We repeat experiment 10, making a moderately good reconstruction of a man, but this time without trying to use salvaged material.
Now, according to the generally accepted interpretation of quantum theory, there is in principle as well as in practice no way to "tag" individual particles, e.g. the atoms or molecules of a man's brain; equivalent particles are completely indistinguishable, and in general it does not even make sense to ask whether the atoms of the reconstructed body are the "same" atoms that were in the original body. Those unfamiliar with the theory, who find this notion hard to stomach, may consult any of the standard texts.
If we accept this view, then a test of individuality becomes still more difficult, because the criteria of identity of material substance and continuity of material substance become difficult or impossible to apply.
Experiment 12.
We discover how to grow or to construct functional replicas of the parts of the brain - possibly biological in nature, possibly mechanical, but at any rate distinguishable from natural units by special tests, although not distinguishable in function. The units might be cells, or they might be larger or smaller components. Now we operate on our subject from time to time, in each operation substituting some artificial brain parts for the natural ones. The subject notices no change in himself, yet when the experiment is finally over, we have in effect a "robot"!
Does the "robot" have the same identity as the original man?
Experiment 13.
We perform the same experiment as 12, but more quickly.
In a single, long operation, we keep replacing natural brain components with artificial ones (and the rest of the body likewise) until all the original bodily material is in the garbage disposal, and a "robot" lies on the operating table, an artificial man whose memories and personality closely duplicate those of the original.
Perhaps some would feel the "robot" was indeed the man, basing the identity in the continuity, on the fact that there was never a sharp dividing line in time where one could say man ended and robot began. Others, well steeped in democracy and willing to apply political principles to biology, might think the robot was not the man, and ceased to be the man when half the material was artificial.
The subject himself, before the operation, would probably regard it as a death sentence. And yet this seems odd, since there is so little real difference between experiments 13 and 12; 13 merely speeds things up. Perhaps sufficient persuasion could convince the subject that the operation did not represent death; he might even be made to prefer a single operation to the nuisance of a series of operations.
Experiment 14.
We assume, as in the previous two experiments, that we can make synthetic body and brain components. We also assume that somehow we can make sufficiently accurate nondestructive analyses of individuals. We proceed to analyze a subject, and then build a replica or twin of him, complete with memories.
Does the identity of our subject now belong equally to the "robot" twin? It might seem absurd to say so, but compare the previous experiment. There is scarcely any difference, especially since in experiment 13 the subject was under anesthesia during the operation; experiment 13 was virtually equivalent to destroying the subject, then building a robot twin. The only real difference between experiments 13 and 14 is that in experiment 14 both the original and the duplicate survive.
Experiments 15, 16, and 17.
We repeat experiments 12, 13, and 14 respectively, but instead of using artificial parts we use ordinary biological material, perhaps obtained by culturing the subject's own cells and conditioning the resultant units appropriately. Does this make any difference?
In logic, one would think perhaps not, but blood is thicker than water. Some people might make a different decision on 15 and 16 than on 12 and 13.
Experiment 18.
We assume the truth of an assertion sometimes heard, viz., that in certain types of surgery a patient under certain types of anesthesia suffers pain, although he does not awaken and afterwards does not remember the pain. The experiment consists in performing such an operation.
Most of us do not fear such operations, because we remember no pain in previous experiences, and because authoritative persons assure us we need not worry. Even a warning that the pain under anesthesia is real is unlikely to disturb us much, if we are not of very nervous temperament. Still less do we fear ordinary deep anesthesia, in which there seems to be no pain on any level, even though for the conscious mind this gulf is like that of death. Yet a child, or a person of morbid imagination, might be intensely frightened by these prospects.
Thus again we note a possible discrepancy between the logical and the psychological.
Experiment 19.
A Moslem warrior is persuaded to give his life joyfully in a "holy war," convinced that the moment his throat is cut he will awaken in Paradise to be entertained by houris.
We draw the obvious but useful conclusion that, from the standpoint of present serenity, it is merely the prospect of immortality that is important.
Experiment 20.
We pull out all the stops, and assume we can make a synthetic chemical electronic mechanical brain which can, among other things, duplicate all the functions of a particular human brain, and possesses the same personality and memory as the human brain. We also assume that there is complete but controlled interconnection between the human brain and the machine brain: that is, we can, at will, remove any segments or functions of the human brain from the joint circuit and replace them by machine components, or vice versa.
In a schematic sense, then, we envisage each of the two brains, the biological one and the mechanical one, as an electronic circuit spread out on a huge "bread board" with complete accessibility. From the two sets of components, by plugging in suitable leads, we can patch together a single functioning unit, the bypassed elements simply lying dormant.
To make the picture simpler and more dramatic, let us also assume the connections require only something like radio communication, and not a physically cumbersome coupling.
We might begin the experiment with the man fully conscious and independent, and the machine brain disconnected and fully dormant. But now we gradually begin disconnecting nerve cells or larger units in the man's brain, simultaneously switching in the corresponding units of the machine. The subject notices no change - yet when the process is completed, we "really" have a machine brain controlling a "zombie" human body!
The machine also has its own sensory organs and effectors. If we now cut off the man's sensory nerves and motor leads and simultaneously activate those of the machine, the first subjective change will occur, namely, an eerie transportation of the senses from one body to another, from the man's to the machine's. This might be enjoyable: perhaps the machine's sense organs are more versatile than the man's, with vision in the infra-red and other improvements, and the common personality might feel wonderful and even prefer to "live" in the machine.
At this stage, remember, the man is entirely dormant, brain and body, and the outside observer may be inclined to think he is looking at an unconscious man and a conscious machine, the machine suffering from the curious delusion that it is a man controlling a machine. Next, we reactivate the components of the man's brain, either gradually or suddenly, simultaneously cutting off those of the machine, but leaving the machine's sensors plugged in and the sensors of the human body disconnected. The subject notices no change, but we now have a human brain using mechanical senses, by remote control. (We disregard such details as the ability of the human optical center to cope with infra-red vision, and the duplication of the new memories.)
Finally, we switch the human effectors and sensors back in, leaving the man once more in his natural state and the machine quiescent.
If we perform this sort of exchange many times, the subject may become accustomed to it, and may even prefer to "inhabit" the machine. He may even view with equanimity the prospect of remaining permanently "in" the machine and having his original body destroyed. This may not prove anything, but it suggests once more that individuality is an illusion.
Discussion and Conclusion.
In discussing these hypothetical experiments we have touched on various possible criteria of individuality - identity of material substance, continuity of material substance, identity of personality and memory, continuity of personality and memory - and seen that none of these is wholly satisfactory. At any rate, none of these, nor any combination, is both necessary and sufficient to prove identity.
One cannot absolutely rule out the possibility that we have missed the nub of the matter, which may lie in some so far intangible essence or soul. However, such a notion seems inconsistent with the ease with which man can instigate, modify, and perhaps actually create life, and with several of our experiments.
The simplest conclusion is that there is really no such thing as individuality in any profound sense. The difficulty arises from our efforts first to abstract generalities from the physical world, and then to regard the abstractions, rather than the world, as the basic reality. A rough analogy will help drive home the point:
The classification "man" is useful, but not sharply definable. Is a freak a man? Is an aborted fetus a man? Is a pre-Neanderthal or other "missing link" a man? Is a corpse a man if some of the cells are still alive? And so on. A label is handy, but objects may be tagged arbitrarily. In the physical world there is no definite collection of objects which can be called "men," but only shifting assemblages of atoms organized in various ways, some of which we may choose to lump together for convenience. Let us then cut the Gordian knot by recognizing that identity, like morality, is man-made and relative, rather than natural and absolute. Identity, like beauty, is partly in the eye of the beholder. It is only partly existent, and partly invented. Instead of having identity, we have degrees of identity, measured by some criteria suitable to the purpose.
The result is wonderful: we have lost our souls, but gained heaven, in a certain sense. Perhaps few of us, even if intellectually convinced that identity is an illusion and death therefore unimportant, may be able to translate this into emotional acceptance, or will want to. But we can now persuade ourselves that death need never be regarded as absolutely final - since it is always possible, at some distance in space, time, and matter, for reasonably close duplication or resuscitation to occur - that is, for physical reincarnation, with memory or without. This possibility can dull the edge of desperation for those unable to obtain first-class freezer accommodations for themselves or their families.
[40 min]
Scientists Are Giving Dead Brains New Life. What Could Go Wrong?
In experiments on pig organs, scientists at Yale made a discovery that could someday challenge our understanding of what it means to die.
Matthew Shaer, July 2, 2019
A few years ago, a scientist named Nenad Sestan began throwing around an idea for an experiment so obviously insane, so “wild” and “totally out there,” as he put it to me recently, that at first he told almost no one about it: not his wife or kids, not his bosses in Yale’s neuroscience department, not the dean of the university’s medical school.
Like everything Sestan studies, the idea centered on the mammalian brain. More specific, it centered on the tree-shaped neurons that govern speech, motor function and thought — the cells, in short, that make us who we are. In the course of his research, Sestan, an expert in developmental neurobiology, regularly ordered slices of animal and human brain tissue from various brain banks, which shipped the specimens to Yale in coolers full of ice. Sometimes the tissue arrived within three or four hours of the donor’s death. Sometimes it took more than a day. Still, Sestan and his team were able to culture, or grow, active cells from that tissue — tissue that was, for all practical purposes, entirely dead. In the right circumstances, they could actually keep the cells alive for several weeks at a stretch.
When I met with Sestan this spring, at his lab in New Haven, he took great care to stress that he was far from the only scientist to have noticed the phenomenon. “Lots of people knew this,” he said. “Lots and lots.” And yet he seems to have been one of the few to take these findings and push them forward: If you could restore activity to individual post-mortem brain cells, he reasoned to himself, what was to stop you from restoring activity to entire slices of post-mortem brain?
To do so would be to create an entirely novel medium for understanding brain function. “One of the things we studied in our lab was the connectome — a kind of wiring map of the brain,” Sestan told me. Research on the connectome, which comprises the brain’s 90 billion neurons and hundreds of trillions of synapses, is widely viewed among neuroscientists as integral to understanding — and potentially treating — a range of disorders, from autism to schizophrenia. And yet there are few reliable ways of tracing all those connections in the brains of large mammals. “I thought, O.K., let’s see if this” — slices of cellularly revived brain tissue — “is the way to go,” Sestan said.
In 2012, Sestan approached two members of his lab, Mihovil Pletikos and Daniel Franjic, and asked them to assist him on the project. Through the spring of 2014, the scientists, often laboring in time they stole from other projects, managed to develop a customized fluid that could preserve centimeter-thick chunks of mouse, pig and human brain for long periods. “Six days was our record,” Sestan recalled. “Six days, and the cells were still culturable.” But there was a hitch: The tissue stayed intact only when the samples were stored in a fridge. Once they were removed and brought to room temperature (any accurate modeling of neuronal function would have to occur at 98.6 degrees Fahrenheit), decomposition rapidly set in.
The primary issue appeared to be one of oxygenation. Mammalian brains are tangled knots of arteries and capillaries, each of which is instrumental in circulating blood (and with it, oxygen and nutrients) throughout the organ. In slicing an entire brain into extremely thin leaves of tissue, the delicate interior architecture was decimated. But Sestan is stubborn, several of his colleagues later told me — in the manner of a dog locking his jaws on a length of knotted rope, he has trouble letting things go. “I get an idea, and I want to finish it,” he admitted. “I have to finish it.” The experiment, he went on, “was constantly on my mind. Like, What is the solution here?”
One afternoon, he dropped by Yale’s pathology department to discuss an unrelated issue with a colleague, Art Belanger, the manager of the university’s morgue at the time. “I look over, and there’s this human brain in a sink, mounted upside-down,” Sestan recalled. As he watched, preservative from a nearby plastic bottle dripped through a few lines of tubing and into the organ’s arteries. The rig, a so-called gravity feed, was being used to “fix” the brain, Belanger explained — to preserve it for further study. Sestan nodded. In his lab, he frequently fixed organs, usually by freezing the specimens or immersing them in formaldehyde. “Trust me,” Belanger told Sestan. “Perfusion is much more effective.”
In contrast to immersion, perfusion leverages the existing vascular network — it mimics the flow of blood through the organ. The resulting fixation is more uniform and drastically faster than traditional methods. And if it’s done quickly enough post-mortem, it can prevent cellular decomposition. “You don’t see any breakdown of tissue; you don’t see any bacterial growth,” Belanger told me recently. “Everything just sort of gets put on pause.”
Sestan stopped in front of the gravity feed, eyes wide. Maybe, he thought, he had been thinking about the problem in the wrong way. Maybe the solution didn’t lie in slices of brain, but in an entire brain, perfused the way Belanger was perfusing this one, with hemoglobin-rich fluid standing in for a preservative. “It was my light-bulb moment,” he said. (Belanger told me: “For 30 years, I’d waited to see a scientist go screaming down the hallway, screaming, ‘Eureka!’ That was the moment. Finally.”) But soon enough, Sestan’s euphoria was followed by a dawning awareness of where the experiment might take him. If the path to cellular restoration really did lie in the perfusion of a whole brain, his experiment would be entering entirely unexplored territory. “It’s kind of amazing, considering everything that came later, but that was the origin,” Sestan told me. “We didn’t want to restart life, you know?”
As long as scientists have understood the role of the mammalian brain, there have been efforts to reanimate it. “To conduct an energetic fluid to the general seat of all impressions,” the Italian physicist Giovanni Aldini wrote at the turn of the 19th century, “to continue, revive, and, if I may be allowed the expression, to command the vital powers — such are the objects of my research.”
In his 1803 book, Aldini describes decapitating an ox and connecting the head to a rudimentary battery; almost immediately, the head began to violently shiver, as if undergoing some kind of seizure. Later, he moved on to humans. “The left eye actually opened,” he wrote of the murderer George Forster, whose recently executed corpse was provided to him by the British government for experimentation. (When Aldini pressed a conducting rod to Forster’s rectum and ear, the muscle contractions “so much increased as almost to give an appearance of reanimation,” the scientist bragged.)
What Aldini failed to grasp, of course, is that life is not powered by electricity alone. It is powered by blood and oxygen, by gases and acids, by an impossibly intricate symphony of cells that die and regenerate and evolve and grow as we do. And it would be more than 150 years before technology had advanced to the point at which it was possible to observe, let alone duplicate, the most basic of those functions.
In the latter half of the 20th century, a new era of brain research was made possible by inventions like microelectrodes that allowed scientists to listen to neurons communicating and cutting-edge devices like functional magnetic resonance imaging scanners, which allow researchers to track blood flow and neuronal activity in the brain, and to learn how the brain responds to injury. Scientists eventually made great strides on the cellular level: In 1982, Takaaki Kirino, a Japanese researcher, published a groundbreaking paper documenting “delayed neuronal death” in Mongolian gerbils. As Kirino noted, many of the animals’ brain cells apparently remained intact long after blood flow had been cut off to the brain. Later, the same phenomenon was observed in post-mortem human cerebral tissue. And in 1991, scientists discovered that the neurons in the brains of lab rats euthanized up to three hours earlier still retained significant electrical activity. Collectively, the research proved that brain death wasn’t a single event. It happened in gradual steps. And precisely because it was gradual, scientists found that they could delay it or reverse parts of the process altogether — perhaps not as drastically as Giovanni Aldini envisioned, but no less emphatically.
Culturing cells from dead tissue was just a small part of it: Studies showed that the brain was far more resilient than had been understood. It could, for example, recover neuronal function after a half-hour of oxygen and blood deprivation — in other words, it could be taken offline and turned back on again. “What’s happened, I’d argue,” says Christof Koch, the president and chief scientist at the Allen Institute for Brain Science, “is that a lot of things about the brain that we once thought were irreversible have turned out not necessarily to be so.”
In recent years, some scientists have moved from the study of the organic tissue to the wholesale creation of artificial brain matter. Grown from human stem cells reprogrammed to act like neurons, brain organoids, or “mini brains,” can mimic some of the functions of their biological counterparts — last year, for example, the biologist Alysson Muotri announced that his lab at the University of California had grown brain organoids with neurons that fired at a level consistent with that of a preterm infant. Muotri has said he hopes to use the creations to research brain function and formulate disease models without buying lab animals or expensive specimens from brain banks. “The potential uses are vast,” he has said.
So, too, are the ethical quandaries. Writing in his forthcoming book on the biological origins of consciousness, “The Feeling of Life Itself: Why Consciousness Is Widespread but Can’t Be Computed,” Koch argues that the chance that an advanced organoid “experiences anything like what a person feels — distress, boredom or a cacophony of sensory impressions — is remote. But it will feel something.” Ideally, Koch adds, “it would be best if this tissue were anesthetized.”
To Sestan and others, there is a mandate to keep pushing, not least because of what it might mean to the world at large: more diseases combated, more treatments developed, more lives saved and, above all, a fuller glimpse of a dauntingly complex organ. The brain remains “the most mysterious” of all the organs, as Sestan put it to me. “The least — what is the right word? Let’s see — well understood.” He went on: “If you’re nuts enough to make the brain the thing you study, you must accept that there will always be more questions than answers. You’ll always be searching. Always.”
For the pasthalf-decade, Sestan has worked out of the same small office in Sterling Hall, in the heart of Yale’s medical campus. The room has one arrow-slit window, which is almost always shuttered, and a wraparound desk buried under a minor Everest of unread journals. Opposite are his sole concessions to décor: a blue Ikea couch and a pillow for lumbar support, necessities for the evenings he opts to write through the night rather than return to the Madison home he shares with his family. “I’m a naturally restless person,” Sestan told me. “High levels of anxiety, high levels of nervousness. But having that quiet, that peace, it centers me. Focuses me.”
Until this year, Sestan was best known as the senior author of the first full genetic survey of the developing human brain; the paper, published in Nature, earned him a raft of awards, including the prestigious Constance Lieber Prize for Innovation in Developmental Neuroscience, which is given out every two years to a pioneering neuroscientist. “I have rarely seen a scientist be able to identify what the field needs better than Nenad, or to address that void with creative ideas,” one of his colleagues told me. “He takes these seemingly disparate observations and synthesizes them into something completely novel. That, to me, is what constitutes a great thinker.”
Stubbornly, Sestan does not hold himself like a great thinker. He likes fart jokes. He says “Holy guacamole!” more than you’d expect. He drives a rusty Subaru, which he parks on the streets surrounding the lab, declining to pay what he views as the “extortionate” fee for the med-school lots. The first time I met him, he held the Subaru’s key fob up to his head and explained that the fat in his brain, acting as a conductor, would allow him to lock the car from more than a block away. He depressed his thumb; sure enough, the Subaru gave an obliging beep. “I learned about that on YouTube,” he told me. “YouTube! It’s like, Holy guacamole!”
A native of Zemunik Donji, a village not far from the Dalmatian coast of Croatia, Sestan had what he calls “the most perfect upbringing you could imagine.” His father was a sergeant in the Yugoslavian Navy, and his mother was a part-time postal worker; he spent much of his childhood playing in the farmland that surrounds Zemunik. When he was 11, his mother bought him a subscription to a medical encyclopedia series. He was entranced. School had been hard for him: He suffered from what he suspects now were dyslexia and attention-deficit disorder. “But I liked systematic things,” he said. “My brain worked fine that way: From A to B to C.”
Paging through the books, he came across an encyclopedia article by an anatomist named Ivica Kostovic, who would later serve as his mentor in medical school. “Kostovic had done all these dissections, all this work on the human brain, and he wrote that there was no subject more fascinating,” Sestan told me. “I said, ‘I’m going to study the human brain, and I’m going to do it with this man.’ ”
It took him a while to get there. By his own admission, he partied maybe more than he should have; he discovered Iron Maiden, grew his hair long and founded his own band, called Twilight Zone. Before his senior year of high school, as he was planning to eventually leave for college in Zagreb, he learned that his girlfriend, soon to be a sophomore, was pregnant. “I wanted to marry her, but her father goes: ‘She’s too young. Let’s wait,’ ” Sestan said. They dated long-distance for two years; when she graduated, she and their son briefly joined Sestan in the capital, where Sestan set about establishing himself as a neuroscientist. He was a co-author of two papers that were among the first to locate, in the developing human brain, the enzyme that makes nitric oxide, which functions as a transmitter between neurons.
Then came the war years. In the early 1990s, Sestan recalls that his hometown was surrounded by Croatian Serbs and troops from the Yugoslav People’s Army; in the fighting, his childhood home was decimated. “My family, my girlfriend, my son, they fled to Slovenia, became refugees,” Sestan told me. But Zagreb was largely spared, and Sestan was able to stay in the capital to continue his studies. (His family’s home in Zemunik has since been rebuilt.)
In the winter of 1994, Sestan, still several months from earning his medical degree, convened a meeting to discuss his enzyme research. His mentor, Kostovic, who had become the deputy prime minister of the republic, was in attendance. “The conversation was basically: ‘O.K., how do we prove this is correct? We need to conduct molecular tests, and we can’t do it here. We don’t have the equipment we need,’ ” Sestan recalled. But Yale, which offered several fellowships to promising foreign neuroscientists, did. “My colleague, the guy I’d written the paper with, said: ‘I have older kids, and a family. Nenad should go.’ ”
At Yale, Sestan joined a lab run by the renowned neuroscientist Pasko Rakic, then the head of the university’s neuroscience program. “I’m in my 80s now, and I’ve worked with a lot of students,” Rakic told me. “Some of those students, they’re content to sit in place, to do the same thing as everyone else. Nenad was not like that. He always wanted the new thing. The next thing.” Rakic is famous in scientific circles for his research on the cerebral cortex, the center of information processing in the brain. Under his tutelage, Sestan published widely on gene expression and cell development in the cerebral cortex, attracting the notice of the department’s hiring committee. “I think people saw what I saw: how much Nenad was capable of,” Rakic told me. By the summer of 2002, Sestan had been made an assistant professor and given a lab of his own in Sterling Hall, along with a half dozen researchers and postgraduates. He was 32.
The demonstration in the Yale morgue inspired Sestan, and with the help of his team, he set about obtaining all the relevant literature on perfusion, including a 1964 study involving dog brains that had been perfused with whole blood. It wasn’t an apples-to-apples comparison: The animals in those experiments had never been truly dead, and the brains hadn’t been removed from the bodies. But it was something. “If you look back at my notes from that period, you can see a lot of extrapolation,” Sestan told me. “There was no exact precedent, but there was stuff that seemed close. And it kept me going.”
As modern medical technologies go, perfusion is a relatively old one: The first perfusion pump, invented in the 1930s by the Nobel Prize-winning scientist and Nazi sympathizer Alexis Carrel and his close friend, the aviator Charles Lindbergh, was used to maintain blood circulation in cat thyroids during a series of transplant operations. Successive generations of engineers have refined and automated Carrel and Lindbergh’s “artificial heart” — if you’ve had open-heart surgery in the past quarter century, your doctors probably had a perfusion system on hand to keep the blood flowing through your brain.
This type of perfusion, performed on a living organ still housed in the host body, is known as “in vivo.” With current technology, it is relatively easy to achieve. “Ex vivo” perfusion, however, is considered by scientists to be far more challenging, while significant attempts to restore metabolic function through a post-mortem ex vivo perfusion of a whole brain are so rare as to be essentially unheard-of. (The most famous attempt was made by the Soviet scientist Sergei Brukhonenko, who used a circulation machine to “revive” a decapitated dog, as documented in the 1940 film “Experiments in the Revival of Organisms,” though many suspect that the footage was doctored.) “You say to a scientist that you want to do this, they’ll think you developed psychosis,” Sestan told me.
Sestan was determined to think like a scientist, not a philosopher. The existential questions interested him far less than the practical ones. “Our goal, our intention, was to do basic biology,” he told me. “And we had to be focused on what we were doing, because it was so important that everything was done correctly, that all the data was solid. When you let your imagination go berserk, when your mind wanders, you make mistakes, and one thing that I knew was that this was likely going to be the hardest thing, technically speaking, I’d ever done, and we couldn’t afford any mistakes.”
Still, as Sestan acknowledged to me, the project was an outlier for him. He felt compelled to put certain safeguards in place: He added “blockers” to the perfusate, to prevent the rise of electrical activity should the experiment succeed in restoring the neurons to do anything resembling consciousness; later, for the same reason, he began keeping a syringe full of a powerful anesthetic in his lab.
The technical hurdles were immense: To perfuse a post-mortem brain, you would have to somehow run fluid through a maze of tiny capillaries that start to clot minutes after death. Everything, from the composition of the blood substitute to the speed of the fluid flow, would have to be calibrated perfectly. In 2015, Sestan struck up an email correspondence with John L. Robertson, a veterinarian and research professor in the department of biomedical engineering at Virginia Tech. For years, Robertson had been collaborating with a North Carolina company, BioMedInnovations, or BMI, on a system known as a CaVESWave — a perfusion machine capable of keeping kidneys, hearts and livers alive outside the body for long stretches. Eventually, Robertson and BMI hoped, the machine would replace cold storage as a way to preserve organs designated for transplants.
For now, one of the few available machines — the third generation of the CaVESWave system — was in Robertson’s lab in Blacksburg, Va.; a majority of the test subjects were pig organs obtained from a nearby slaughterhouse. Sestan was intrigued, and when he traveled to the Washington area that February to present a paper on his gene-expression research, he arranged a side trip to Blacksburg to meet with Robertson in person. “I couldn’t get there fast enough,” Sestan told me. On Interstate 81, near Roanoke, he was pulled over by a state trooper. “I said: ‘I’ll be honest with you, sir. All my life, I’ve hated driving behind big trucks. They scare me. It’s my paranoia.’ ” The trooper thanked him for his honesty and wrote him a ticket anyway.
Back in New Haven, Sestan showed pictures of the machine to his colleagues. Some questioned his sanity. (“This isn’t a joke, man!” Sestan remembers one telling him.) Others, busy with their own projects, were wary of getting involved. “And that was when I found Zvonimir,” Sestan recalled. Zvonimir is Zvonimir Vrselja, a fellow Croat who was 28 at the time. Angular and bright-eyed, Vrselja specialized in radiology; he has published on the vasculature of the brain and cerebral pulsatility — the way that blood moves through the cortex. In late 2015, a colleague of Vrselja’s in Croatia reached out to Sestan and suggested that the two scientists talk. Zvonimir’s “skill set was exactly what I wanted,” Sestan told me. “Exactly.”
A few months later, Vrselja moved to New Haven; together, he and Sestan reached out to a third scientist: Stefano Daniele, a 25-year-old who had spent years researching brain degeneration in patients with Parkinson’s disease. Daniele was skeptical. In joining what was then still a top-secret project, he would have to rearrange his plans for his dual M.D.-Ph.D. degree. “Nenad took me aside,” Daniele told me, “and said: ‘I have never done anything like this; we have no data. But if it works, it’s going to change neuroscience.’ ”
In the spring of 2015, Sestan made the first of several payments on a BMI machine, which Robertson and the company estimated would take half a year to fabricate. In the meantime, Daniele and Vrselja could test out a version of the system housed at Virginia Tech. (It was decided that Sestan, with his academic commitments, would remain in New Haven.)
All three scientists were adamant that they had never once considered carrying out any tests on human specimens. The regulatory bar was too high, and as Sestan put it to me, when it comes to human tissue, post-mortem or not, “there has to be extreme justification, from an ethical standpoint. Which is exactly how it should be.” To a slightly lesser degree, the same is true of other large mammals. But dead animals are a different matter. And BMI had its relationship with the slaughterhouse near Virginia Tech. It wouldn’t be a problem, Sestan figured, to arrange for the purchase of pig brain tissue — porcine brains, after all, are usually discarded after the animal’s death.
“We knew that with a project like this one, it was going to be trial and error,” Vrselja told me. “Lots of trial and error. And to kill that number of animals, it just seemed absurd.” But if the slaughterhouse would sell them the equivalent of refuse, there would be no ethical quandary at all. “I remember we went to the slaughterhouse manager, and he shrugged. He was like, ‘Are you going to pay me?’ ” When they said they would, the manager replied, “Great, you can work out of my office.”
Almost immediately after arriving in Virginia, Vrselja and Daniele ran into a very big problem. “To perfuse something, you have to know how it works,” Vrselja recalled. “You go to an anatomy class, and that’s what you learn — how an organ functions. But there is not a lot of good literature on pig vasculature. And definitely not about how the blood circulates in a pig’s brain. We had to figure that out from scratch.”
Every morning for several weeks, the scientists woke up around 4:30 to be at the slaughterhouse as the first pigs were led to the killing floor. While they waited, the animals were stunned, killed, eviscerated and stripped of usable meat; later, Daniele and Vrselja would run carrying a bloody pig head in a bag to the manager’s office, where they would use a pump to empty the excess blood from it. Finally, placing the skull on ice, they would drive it back with them to the lab in Blacksburg.
It was difficult not to get discouraged. The architecture of the brains was only half of it: The scientists also had to learn to remove the skull in a way that preserved the organ’s vital architecture, like the arteries. And initially they were working without neurosurgical tools. “We had an oscillating saw from Home Depot,” Daniele said. “It was like sawing into the unknown, because you had to go millimeter by millimeter, and the whole key was to go as close as possible to the brain but not pierce into it, because you actually didn’t know where the floor was, where the brain was.”
With every two steps forward, they seemed to be taking another one back. By running food coloring through the arteries of the brain, Vrselja and Daniele could see how blood traveled through the organ, but the arteries split and joined at such irregular intervals that it took days to figure out how each one influenced the circulation of blood. “Every time we thought that we had it down,” Daniele told me, “a weird branch would come up and steal the circulation from the brain, and then it would leak out that way.”
By the 20th brain, they had a sense of which arteries connected to which; by the 40th, they had worked out what vessels needed to be closed off — and what sections of the skull needed to remain attached. “I remember feeling like shit, physically, because we were up at 4 every morning, going to bed at midnight and doing the same thing again,” Vrselja told me. “But eventually, there was progress.”
Sestan and his team would end up modifying nearly every aspect of BMI’s machine. Still, both the original and the current iteration, which Yale is seeking a patent for using the name BrainEx, work in fundamentally the same way. First, the brain is mostly freed from the skull; all the dangling arteries, save the carotids, are cauterized or sutured. Next, the organ is flushed of residual blood. At the same time, an amount of perfusate equivalent to a bottle of wine is brought to body temperature in the machine’s reservoir and oxygenated — as with real blood, oxygenation turns the perfusate a darker, scarlet red.
Once the fluid — the present form of which includes antibiotics and nine different types of cytoprotective agents — is ready, the brain is lowered into a plastic case the scientists have nicknamed “the football” and connected via the carotids. A small thermal unit (a miniature air-conditioner and heater) sits under the football, controlling the temperature of the organ; the pressure and speed of the perfusate, meanwhile, are governed by a type of pump. With a dull whir, the fluid begins to circulate across the arteries, capillaries and veins of the brain in a loop, exiting on each circuit through a dialysis unit that “cleans” any waste products and through a filter that removes any naturally occurring bubbles.
Perhaps the most innovative modification involved fluid mechanics, one of Vrselja’s specialties in graduate school. As the British mathematician John Womersley managed to quantify more than half a century ago, blood does not circulate through our arteries at a uniform rhythm — it circulates in pulses, in concert with the shudder of our hearts. To account for that dynamic, the BMI unit had shipped with an automated “pulse generator,” a device that replicates the heartbeat’s pulsatility in the organs.
But the pulse generator’s settings proved unsuitable for brains, which have a different flow pattern than the rest of the body. Before Sestan’s team adjusted the settings, the fluid might not completely permeate the vasculature of the organ, leaving parts of the brain essentially untreated. In such tissue, Daniele told me, “you’d end up with this sludgy, white yogurt-ish substance. It was a mess.” Conversely, if the pressure was too high, “the brain could just physically not stand it.” The organ fell apart.
By that summer, Vrselja and Daniele had fine-tuned the pulse generator and attached a number of custom sensors, which ran on software designed by Vrselja; the technology allowed them to experiment more easily, and widely, with different settings. “A good way of putting it,” Vrselja told me, “is we needed to figure out millions of years of evolution in a very short window of time.”
As the weeks went on, Vrselja and Daniele discovered something encouraging: The interior brain tissue had a moist gray hue, as a living organ would — a sign that some cellular function had been restored. But to know for sure, they would have to perform the requisite lab work.
Over the course of that spring, they fixed brains from separate specimen sets and delivered them to Sestan. “It was the most astonishing thing, ” Sestan recalls. Active brain cells can have a variety of shapes, depending on the type and function. But dead or dying or inactive brain cells tend to look alike, as if a bomb has been set off somewhere in the nucleus and the entire structure has imploded from within. In the face of almost everything that was known about the brain — in the face of centuries of scientific research — the cells from the experimental group were metabolically active. Sestan, hunched over the microscope, could hardly believe what he was seeing. “Oh, my God,” he remembers whispering to himself.
Soon, the scientists had ratcheted up the length of the perfusions, from one hour to two or three, and Sestan found himself staring down a fresh and unusual dilemma. In and of itself, he knew, cellular function is not indicative of life, just as Giovanni Aldini’s galvanic experimentation did not amount to the resurrection of an animal’s mind. And yet by all accounts, the longer Vrselja and Daniele perfused the pig brains, and the better they got at the process, the more brain cells were restored.
In 2016, Sestan employed a machine known as a BIS, or a bispectral index monitor, which is used in hospitals to measure how deeply a patient is “under” during surgery. BIS results are categorized on a scale from zero to 100: Zero is the absence of electrical activity — a chunk of wood would score a zero on the bispectral index — while 90 to 100 is consistent with full cerebral function in a living human. (A person between 40 and 60, target numbers for general anesthesia, will be unresponsive to most stimuli.)
That summer, Sestan was preparing a grant application when Vrselja and Daniele summoned him to the perfusion room. The BIS readout had just hit 10 — at the low end of what is called burst suppression, a stuttering pattern often observed in human patients in a deep coma. “That level, it’s not associated with any kind of cognition,” Daniele told me. “The brain is considered to be entirely inactive. Dead.”
And yet as low as the score was, it wasn’t zero. “I just thought, Yeah, O.K., forget it,” Sestan recalled. “I’m not taking any chances. I said: ‘Unplug the machine. Stop the experiment until we can figure out what’s happening.’ ” That same day, he wrote two emails. The first was to a contact at the National Institutes of Health. The second was to Stephen Latham, the director of the Yale Interdisciplinary Center for Bioethics.
Latham is tall and ruddy, with neatly parted gray hair and a big, gaptoothed smile. Trained as an attorney, he speaks precisely, often in complete paragraphs, as if he is weighing each word before it leaves his mouth. “I remember that I shared Nenad’s reaction, which was, ‘No, we can’t have this happening,’ ” he told me recently. “If there is even a possibility of consciousness, yeah, you have got to stop the experiment.”
Legally, Latham knew, Sestan and his team weren’t in jeopardy. “The way our existing laws on animal research work — and I’ll stipulate that these are laws that many animal ethics people take issue with — you can kill an animal,” Latham told me. “You can give an animal a disease like cancer, you can let it die and you can dissect that animal to see what happened.” Sestan hadn’t killed any animals; he had merely recycled flesh that would have otherwise been disposed of. “Nenad wasn’t even at the boundary of what isn’t permissible,” Latham said.
And yet in another way, Sestan had long since passed any known boundaries. Cellularly revived dead tissue is “an in-between category,” said Nita Farahany, a law scholar and ethicist at Duke University. “It’s a total gray zone.” There were no rules in place to follow, and no rules to break.
For Sestan, the thorniest issue centered on consciousness and whether the Yale team, inadvertently, might somehow have figured out a way to elicit it from dead flesh. In 2019, brain death — and thus complete loss of consciousness — has become something of a moving target: Research has shown that patients we once thought were in deep comas as a result of a traumatic brain injury are actually able to communicate. As Christof Koch, the neuroscientist, writes, all neurologists agree that electricity in the brain is a prerequisite for thought. But new technologies, including a machine nicknamed the “zip-and-zap,” which uses both EEG monitoring and transcranial magnetic stimulation, have been used to detect brain activity in patients assumed to be in a vegetative state. These machines, Koch writes, challenge “clinicians to devise more sophisticated physiological and behavioral measures to detect the faint telltale signs of a mind.”
As Sestan knew, the chances of real consciousness arising from the perfused brains were slim, thanks to the channel blockers. But there was a worst-case scenario: A partly revived post-mortem brain, trapped in a feverish nightmare, perpetually reliving the very moment of its slaughter. “Imagine the ultimate sensory-deprivation tank,” a member of the N.I.H.’s Neuroethics Working Group told me. “No inputs. No outputs. In your brain, nobody can hear you scream.”
In August, with the experiment now paused, Sestan and his team went to Washington to meet with the members of the N.I.H.’s working group. “It’s fair to say that we were shocked,” the member told me this spring. “Astounded, I suppose.”
The board suggested that Sestan trade in the BIS monitor, which is not made for nonhuman subjects, for a more sensitive electrical monitoring system. And a colleague gave him a name: Rafeed Alkawadri, an expert in invasive intracranial EEG evaluations — a form of electrocorticography, or ECoG, in which the electrodes are connected directly to the brain’s surface rather than the exterior of the head. “Electrocorticography was the way to go, but with ECoG, generally speaking, you’ve got a scalp,” Sestan recalled. “With our experiment, we had no scalp. We said, ‘Let’s get this equipment into the lab.’ ”
A few days later, Alkawadri completed a round of tests on a perfused porcine brain. He saw no “spontaneous global activity” present in the organ or communication between the various parts of the brain; the BIS reading of 10, Alkawadri theorized, was a result of electrical interference produced by the machine.
Still, the incident was not exactly a false alarm. Sestan considered it more like a warning. Remove the channel blockers, he told me, “and you might get a signal” — a real one. I wondered if he had thought about trying it. “No,” he answered quickly. “Not now. And just speaking for myself here, maybe not ever.”
By early 2017, Daniele and Vrselja were again expanding the length of the perfusions, past three hours and then to four. But the brains in the control group couldn’t survive cellularly past 240 minutes, at which point decomposition set in, making comparison to the experimental group impossible beyond that.
After the N.I.H. meeting, Sestan was invited to Duke University to speak with the members of the school’s bioethics faculty and others. “People were aghast,” one person familiar with the meeting told me, “because everyone had this image of a pig’s head on a lab cart, attached to a bunch of hoses and tube, and the pig’s head coming back to life. There was a lot of concern,” the person went on, “that if this was to be made public in the wrong way, it could really be a setback for brain research. Like, decades of setback. It was so easily caricaturized.”
That summer, after a source told me about the Duke meeting, I reached out to Sestan. In a phone call, he called the experiment “the most important thing I’ve ever done, and the most important thing I will ever do,” and mentioned he was preparing to submit a paper to Nature. Once it had been accepted, he went on, he would get back in touch with me; until then, he wasn’t able to comment on the record.
In March 2018, Sestan met again with the N.I.H. Under the impression that everything he said would be kept confidential, he had put together a presentation on his experiment, and while the dozen or so attendees looked on, he clicked through a series of slides showing restored cells from the perfused brains. According to later reports, Sestan, referring to the most recent ECoG data, stressed that he was confident that the brains in his experiment were “not aware of anything.” Still, he went on, he could not speak to what other scientists might do with the research. “Hypothetically, somebody takes this technology, makes it better and restores someone’s [brain] activity,” he said. “That is restoring a human being. If that person has memory, I would be freaking out completely.”
With each meeting, the number of people aware of the project was growing, and Sestan, despite what he described to me as “begging and pleading,” was unable to prevent the publication last spring of an article in the MIT Technology Review, which was apparently based on video of Sestan’s 2018 N.I.H. presentation. Published with a still of a scene from the Steve Martin comedy “The Man With Two Brains,” the article framed Sestan’s work as “a step that could change the definition of death” — a “feat” that “inaugurates a bizarre new possibility in life extension.”
Within hours, the news had been picked up by media outlets around the world. “Scientists keeping pig brains ‘alive’ inside their SEVERED heads in Frankenstein-style research,” read the headline in the British tabloid The Mirror. The conspiracy theorist Alex Jones brought up the experiment on his radio show.
The email flooded in to Sestan’s office. “In case a study comes up and I find myself dying at that time, I volunteer for the brain study,” one read. “That’s right, I give you permission to, upon my untimely death, extract my brain and keep it ‘alive’ as long as you can outside the context of my body.” Another writer chided Sestan for taking measures to prevent the emergence of consciousness. “Progress cannot and should not be held back. ... I suggest you seek private research funding from Silicon Valley, there is many a great powers and influential men who would fund this line of research and see it through to its full potential.” Finally, and most tragic, there were the relatives of patients who suffered brain trauma. What Sestan’s project proved, a mother in New England wrote hopefully, was that “there is no way to know when someone is truly dead.” Sestan told me: “You want to respond to each email, you want to try to explain the science, but you can’t. There are just too many.”
This spring, I flew to New Haven to tour Sestan’s lab. In a show of ceremony, he saved a viewing of the BrainEx for last. “You,” he said proudly, throwing open the door to a converted supply closet, “are the first member of the public to see it.” Roughly eight feet wide and mounted on the shelves of a long metal hospital-style cart, the BrainEx was less a single machine than a bristling collection of individual machines, each connected to the next, in a simulacrum of the human body. Here, the pulse generator — the equivalent of a heart. Here, the filters — mechanized kidneys. There, the device that, like lungs, helped oxygenate the perfusate. “We’ll do our dance,” Daniele said, and he commenced a dry run — sans brain — of the process, miming each step.
“Don’t forget the Kanye,” Daniele joked.
“Our soundtrack,” Vrselja said with a grin.
By any measure, the contents of the paper Sestan and his team published in Nature this April were astonishing: Not only were Sestan and his team eventually able to maintain perfusion for six hours in the organs, but they managed to restore full metabolic function in most of the brain — the cells in the dead pig brains took oxygen and glucose and converted them into metabolites like carbon dioxide that are essential to life. “These findings,” the scientists write, “show that, with the appropriate interventions, the large mammalian brain retains an underappreciated capacity for normothermic restoration of microcirculation and certain molecular and cellular functions multiple hours after circulatory arrest.”
When we spoke in June, shortly before this article went to press, Sestan told me he frequently marveled at the direction the experiment had ultimately taken. “You know, I started out hoping to be able to trace connections,” he said. “But in the last three years, what happened was that the project really became more about death than anything having to do with the connectome.”
“The whole project is testament to the fact that the simplest observations can lead to the most exciting findings,” said Stephen L. Hauser, director of the Weill Institute for Neurosciences at the University of California, San Francisco. “It’s the type of finding that after it is made, it might seem obvious. One reaction could be, ‘Hey, why didn’t we think of that?’ But it took creativity, it took doggedness to get to that point.”
In our conversations, Sestan was always happy to expound on the science behind his experiment but cagier when it came to the implications. In the field of modern neurology, Hauser told me, “you’re constantly trying to dampen down overinterpretation. Often, that’s easy, because what’s being written about it is an incremental change over what’s already been established, or it’s just total baloney. Here, though, with this paper, we have something different: These are truly superb scientists. I think there’s a lot more that we still have to learn; the story’s not yet complete. But this is interesting, real science.”
Sestan did acknowledge that, yes, theoretically there is nothing stopping a scientist from immediately building a perfusion machine that could support a human brain. The BrainEx technology is open-source, and pig and homo sapiens brains have a fair amount in common. And there are plenty of conceivable applications for a human-optimized BrainEx. In addition to being an ideal model for testing out drugs, a portable perfusion system might be used on the battlefield, to protect the brain of a soldier whose body has been grievously injured; it might, in some distant future, become standard equipment for first responders. “The thing is,” Sestan said, “there’s a lot of research left to be done.” His focus now is better understanding how brain cells can be saved after major heart events. He sees no path to human tests. “If you could be absolutely certain you could do this on a post-mortem human brain and not get electrical activity of any kind, then maybe, maybe, we talk more,” he went on. “At the moment, I can’t see justification.”
And yet, as the ethicist and Stanford University law professor Hank Greely argued to me recently, we live in a time of breakneck scientific advancements; in 2019, “what ifs” advance more rapidly to the experimentation stage than ever before. Consider, Greely suggested, the case of the Italian neurosurgeon Sergio Canavero and his associate, the Chinese scientist Xiaoping Ren, who claim to have transplanted a head from one cadaver to another. Undoubtedly, a scientist with fewer scruples than Sestan, fewer moral qualms about human experimentation, will emerge. “Somebody will perfuse a dead human brain, and I think it will be in an unconventional setting, not necessarily in a pure research manner,” Greely told me. “It will be somebody with a lot of money, and he’ll find a scientist willing to do it.”
Greely and Nita Farahany of Duke, along with the young Duke scientist Charles M. Giattino, recently published a long essay in Nature on Sestan’s findings. (Their 2,000-word essay is one of two to appear alongside the paper.) “In our view, new guidelines are needed for studies involving the preservation or restoration of whole brains,” they wrote, “because animals used for such research could end up in a gray area — not alive, but not completely dead.” They noted, “We’re reminded of a line from the 1987 film ‘The Princess Bride’: ‘There’s a big difference between mostly dead and all dead. Mostly dead is slightly alive.’ ”
In the paper, Greely, Farahany and Giattino advocate the adoption of guidelines modeled on those established in 2005 on stem-cell usage. “Looking back, those guidelines really helped shape the field,” Greely told me. “Here, we have nothing. We have serious gaps in the regulatory system. We need to be proactive.”
Sestan, for his part, agrees. “Every one of these decisions,” he told me before I left New Haven, “shouldn’t be up to me alone.” In solving countless technical problems, he knew, he had created an entirely new set of implications for the rest of us to wrestle with. “I shouldn’t decide,” he went on, “what we do or what we shouldn’t do. That’s up to you; it’s up to all of us. We make the decision together.”
Scientists Are Giving Dead Brains New Life. What Could Go Wrong?
In experiments on pig organs, scientists at Yale made a discovery that could someday challenge our understanding of what it means to die.
Matthew Shaer, July 2, 2019
A few years ago, a scientist named Nenad Sestan began throwing around an idea for an experiment so obviously insane, so “wild” and “totally out there,” as he put it to me recently, that at first he told almost no one about it: not his wife or kids, not his bosses in Yale’s neuroscience department, not the dean of the university’s medical school.
Like everything Sestan studies, the idea centered on the mammalian brain. More specific, it centered on the tree-shaped neurons that govern speech, motor function and thought — the cells, in short, that make us who we are. In the course of his research, Sestan, an expert in developmental neurobiology, regularly ordered slices of animal and human brain tissue from various brain banks, which shipped the specimens to Yale in coolers full of ice. Sometimes the tissue arrived within three or four hours of the donor’s death. Sometimes it took more than a day. Still, Sestan and his team were able to culture, or grow, active cells from that tissue — tissue that was, for all practical purposes, entirely dead. In the right circumstances, they could actually keep the cells alive for several weeks at a stretch.
When I met with Sestan this spring, at his lab in New Haven, he took great care to stress that he was far from the only scientist to have noticed the phenomenon. “Lots of people knew this,” he said. “Lots and lots.” And yet he seems to have been one of the few to take these findings and push them forward: If you could restore activity to individual post-mortem brain cells, he reasoned to himself, what was to stop you from restoring activity to entire slices of post-mortem brain?
To do so would be to create an entirely novel medium for understanding brain function. “One of the things we studied in our lab was the connectome — a kind of wiring map of the brain,” Sestan told me. Research on the connectome, which comprises the brain’s 90 billion neurons and hundreds of trillions of synapses, is widely viewed among neuroscientists as integral to understanding — and potentially treating — a range of disorders, from autism to schizophrenia. And yet there are few reliable ways of tracing all those connections in the brains of large mammals. “I thought, O.K., let’s see if this” — slices of cellularly revived brain tissue — “is the way to go,” Sestan said.
In 2012, Sestan approached two members of his lab, Mihovil Pletikos and Daniel Franjic, and asked them to assist him on the project. Through the spring of 2014, the scientists, often laboring in time they stole from other projects, managed to develop a customized fluid that could preserve centimeter-thick chunks of mouse, pig and human brain for long periods. “Six days was our record,” Sestan recalled. “Six days, and the cells were still culturable.” But there was a hitch: The tissue stayed intact only when the samples were stored in a fridge. Once they were removed and brought to room temperature (any accurate modeling of neuronal function would have to occur at 98.6 degrees Fahrenheit), decomposition rapidly set in.
The primary issue appeared to be one of oxygenation. Mammalian brains are tangled knots of arteries and capillaries, each of which is instrumental in circulating blood (and with it, oxygen and nutrients) throughout the organ. In slicing an entire brain into extremely thin leaves of tissue, the delicate interior architecture was decimated. But Sestan is stubborn, several of his colleagues later told me — in the manner of a dog locking his jaws on a length of knotted rope, he has trouble letting things go. “I get an idea, and I want to finish it,” he admitted. “I have to finish it.” The experiment, he went on, “was constantly on my mind. Like, What is the solution here?”
One afternoon, he dropped by Yale’s pathology department to discuss an unrelated issue with a colleague, Art Belanger, the manager of the university’s morgue at the time. “I look over, and there’s this human brain in a sink, mounted upside-down,” Sestan recalled. As he watched, preservative from a nearby plastic bottle dripped through a few lines of tubing and into the organ’s arteries. The rig, a so-called gravity feed, was being used to “fix” the brain, Belanger explained — to preserve it for further study. Sestan nodded. In his lab, he frequently fixed organs, usually by freezing the specimens or immersing them in formaldehyde. “Trust me,” Belanger told Sestan. “Perfusion is much more effective.”
In contrast to immersion, perfusion leverages the existing vascular network — it mimics the flow of blood through the organ. The resulting fixation is more uniform and drastically faster than traditional methods. And if it’s done quickly enough post-mortem, it can prevent cellular decomposition. “You don’t see any breakdown of tissue; you don’t see any bacterial growth,” Belanger told me recently. “Everything just sort of gets put on pause.”
Sestan stopped in front of the gravity feed, eyes wide. Maybe, he thought, he had been thinking about the problem in the wrong way. Maybe the solution didn’t lie in slices of brain, but in an entire brain, perfused the way Belanger was perfusing this one, with hemoglobin-rich fluid standing in for a preservative. “It was my light-bulb moment,” he said. (Belanger told me: “For 30 years, I’d waited to see a scientist go screaming down the hallway, screaming, ‘Eureka!’ That was the moment. Finally.”) But soon enough, Sestan’s euphoria was followed by a dawning awareness of where the experiment might take him. If the path to cellular restoration really did lie in the perfusion of a whole brain, his experiment would be entering entirely unexplored territory. “It’s kind of amazing, considering everything that came later, but that was the origin,” Sestan told me. “We didn’t want to restart life, you know?”
As long as scientists have understood the role of the mammalian brain, there have been efforts to reanimate it. “To conduct an energetic fluid to the general seat of all impressions,” the Italian physicist Giovanni Aldini wrote at the turn of the 19th century, “to continue, revive, and, if I may be allowed the expression, to command the vital powers — such are the objects of my research.”
In his 1803 book, Aldini describes decapitating an ox and connecting the head to a rudimentary battery; almost immediately, the head began to violently shiver, as if undergoing some kind of seizure. Later, he moved on to humans. “The left eye actually opened,” he wrote of the murderer George Forster, whose recently executed corpse was provided to him by the British government for experimentation. (When Aldini pressed a conducting rod to Forster’s rectum and ear, the muscle contractions “so much increased as almost to give an appearance of reanimation,” the scientist bragged.)
What Aldini failed to grasp, of course, is that life is not powered by electricity alone. It is powered by blood and oxygen, by gases and acids, by an impossibly intricate symphony of cells that die and regenerate and evolve and grow as we do. And it would be more than 150 years before technology had advanced to the point at which it was possible to observe, let alone duplicate, the most basic of those functions.
In the latter half of the 20th century, a new era of brain research was made possible by inventions like microelectrodes that allowed scientists to listen to neurons communicating and cutting-edge devices like functional magnetic resonance imaging scanners, which allow researchers to track blood flow and neuronal activity in the brain, and to learn how the brain responds to injury. Scientists eventually made great strides on the cellular level: In 1982, Takaaki Kirino, a Japanese researcher, published a groundbreaking paper documenting “delayed neuronal death” in Mongolian gerbils. As Kirino noted, many of the animals’ brain cells apparently remained intact long after blood flow had been cut off to the brain. Later, the same phenomenon was observed in post-mortem human cerebral tissue. And in 1991, scientists discovered that the neurons in the brains of lab rats euthanized up to three hours earlier still retained significant electrical activity. Collectively, the research proved that brain death wasn’t a single event. It happened in gradual steps. And precisely because it was gradual, scientists found that they could delay it or reverse parts of the process altogether — perhaps not as drastically as Giovanni Aldini envisioned, but no less emphatically.
Culturing cells from dead tissue was just a small part of it: Studies showed that the brain was far more resilient than had been understood. It could, for example, recover neuronal function after a half-hour of oxygen and blood deprivation — in other words, it could be taken offline and turned back on again. “What’s happened, I’d argue,” says Christof Koch, the president and chief scientist at the Allen Institute for Brain Science, “is that a lot of things about the brain that we once thought were irreversible have turned out not necessarily to be so.”
In recent years, some scientists have moved from the study of the organic tissue to the wholesale creation of artificial brain matter. Grown from human stem cells reprogrammed to act like neurons, brain organoids, or “mini brains,” can mimic some of the functions of their biological counterparts — last year, for example, the biologist Alysson Muotri announced that his lab at the University of California had grown brain organoids with neurons that fired at a level consistent with that of a preterm infant. Muotri has said he hopes to use the creations to research brain function and formulate disease models without buying lab animals or expensive specimens from brain banks. “The potential uses are vast,” he has said.
So, too, are the ethical quandaries. Writing in his forthcoming book on the biological origins of consciousness, “The Feeling of Life Itself: Why Consciousness Is Widespread but Can’t Be Computed,” Koch argues that the chance that an advanced organoid “experiences anything like what a person feels — distress, boredom or a cacophony of sensory impressions — is remote. But it will feel something.” Ideally, Koch adds, “it would be best if this tissue were anesthetized.”
To Sestan and others, there is a mandate to keep pushing, not least because of what it might mean to the world at large: more diseases combated, more treatments developed, more lives saved and, above all, a fuller glimpse of a dauntingly complex organ. The brain remains “the most mysterious” of all the organs, as Sestan put it to me. “The least — what is the right word? Let’s see — well understood.” He went on: “If you’re nuts enough to make the brain the thing you study, you must accept that there will always be more questions than answers. You’ll always be searching. Always.”
For the pasthalf-decade, Sestan has worked out of the same small office in Sterling Hall, in the heart of Yale’s medical campus. The room has one arrow-slit window, which is almost always shuttered, and a wraparound desk buried under a minor Everest of unread journals. Opposite are his sole concessions to décor: a blue Ikea couch and a pillow for lumbar support, necessities for the evenings he opts to write through the night rather than return to the Madison home he shares with his family. “I’m a naturally restless person,” Sestan told me. “High levels of anxiety, high levels of nervousness. But having that quiet, that peace, it centers me. Focuses me.”
Until this year, Sestan was best known as the senior author of the first full genetic survey of the developing human brain; the paper, published in Nature, earned him a raft of awards, including the prestigious Constance Lieber Prize for Innovation in Developmental Neuroscience, which is given out every two years to a pioneering neuroscientist. “I have rarely seen a scientist be able to identify what the field needs better than Nenad, or to address that void with creative ideas,” one of his colleagues told me. “He takes these seemingly disparate observations and synthesizes them into something completely novel. That, to me, is what constitutes a great thinker.”
Stubbornly, Sestan does not hold himself like a great thinker. He likes fart jokes. He says “Holy guacamole!” more than you’d expect. He drives a rusty Subaru, which he parks on the streets surrounding the lab, declining to pay what he views as the “extortionate” fee for the med-school lots. The first time I met him, he held the Subaru’s key fob up to his head and explained that the fat in his brain, acting as a conductor, would allow him to lock the car from more than a block away. He depressed his thumb; sure enough, the Subaru gave an obliging beep. “I learned about that on YouTube,” he told me. “YouTube! It’s like, Holy guacamole!”
A native of Zemunik Donji, a village not far from the Dalmatian coast of Croatia, Sestan had what he calls “the most perfect upbringing you could imagine.” His father was a sergeant in the Yugoslavian Navy, and his mother was a part-time postal worker; he spent much of his childhood playing in the farmland that surrounds Zemunik. When he was 11, his mother bought him a subscription to a medical encyclopedia series. He was entranced. School had been hard for him: He suffered from what he suspects now were dyslexia and attention-deficit disorder. “But I liked systematic things,” he said. “My brain worked fine that way: From A to B to C.”
Paging through the books, he came across an encyclopedia article by an anatomist named Ivica Kostovic, who would later serve as his mentor in medical school. “Kostovic had done all these dissections, all this work on the human brain, and he wrote that there was no subject more fascinating,” Sestan told me. “I said, ‘I’m going to study the human brain, and I’m going to do it with this man.’ ”
It took him a while to get there. By his own admission, he partied maybe more than he should have; he discovered Iron Maiden, grew his hair long and founded his own band, called Twilight Zone. Before his senior year of high school, as he was planning to eventually leave for college in Zagreb, he learned that his girlfriend, soon to be a sophomore, was pregnant. “I wanted to marry her, but her father goes: ‘She’s too young. Let’s wait,’ ” Sestan said. They dated long-distance for two years; when she graduated, she and their son briefly joined Sestan in the capital, where Sestan set about establishing himself as a neuroscientist. He was a co-author of two papers that were among the first to locate, in the developing human brain, the enzyme that makes nitric oxide, which functions as a transmitter between neurons.
Then came the war years. In the early 1990s, Sestan recalls that his hometown was surrounded by Croatian Serbs and troops from the Yugoslav People’s Army; in the fighting, his childhood home was decimated. “My family, my girlfriend, my son, they fled to Slovenia, became refugees,” Sestan told me. But Zagreb was largely spared, and Sestan was able to stay in the capital to continue his studies. (His family’s home in Zemunik has since been rebuilt.)
In the winter of 1994, Sestan, still several months from earning his medical degree, convened a meeting to discuss his enzyme research. His mentor, Kostovic, who had become the deputy prime minister of the republic, was in attendance. “The conversation was basically: ‘O.K., how do we prove this is correct? We need to conduct molecular tests, and we can’t do it here. We don’t have the equipment we need,’ ” Sestan recalled. But Yale, which offered several fellowships to promising foreign neuroscientists, did. “My colleague, the guy I’d written the paper with, said: ‘I have older kids, and a family. Nenad should go.’ ”
At Yale, Sestan joined a lab run by the renowned neuroscientist Pasko Rakic, then the head of the university’s neuroscience program. “I’m in my 80s now, and I’ve worked with a lot of students,” Rakic told me. “Some of those students, they’re content to sit in place, to do the same thing as everyone else. Nenad was not like that. He always wanted the new thing. The next thing.” Rakic is famous in scientific circles for his research on the cerebral cortex, the center of information processing in the brain. Under his tutelage, Sestan published widely on gene expression and cell development in the cerebral cortex, attracting the notice of the department’s hiring committee. “I think people saw what I saw: how much Nenad was capable of,” Rakic told me. By the summer of 2002, Sestan had been made an assistant professor and given a lab of his own in Sterling Hall, along with a half dozen researchers and postgraduates. He was 32.
The demonstration in the Yale morgue inspired Sestan, and with the help of his team, he set about obtaining all the relevant literature on perfusion, including a 1964 study involving dog brains that had been perfused with whole blood. It wasn’t an apples-to-apples comparison: The animals in those experiments had never been truly dead, and the brains hadn’t been removed from the bodies. But it was something. “If you look back at my notes from that period, you can see a lot of extrapolation,” Sestan told me. “There was no exact precedent, but there was stuff that seemed close. And it kept me going.”
As modern medical technologies go, perfusion is a relatively old one: The first perfusion pump, invented in the 1930s by the Nobel Prize-winning scientist and Nazi sympathizer Alexis Carrel and his close friend, the aviator Charles Lindbergh, was used to maintain blood circulation in cat thyroids during a series of transplant operations. Successive generations of engineers have refined and automated Carrel and Lindbergh’s “artificial heart” — if you’ve had open-heart surgery in the past quarter century, your doctors probably had a perfusion system on hand to keep the blood flowing through your brain.
This type of perfusion, performed on a living organ still housed in the host body, is known as “in vivo.” With current technology, it is relatively easy to achieve. “Ex vivo” perfusion, however, is considered by scientists to be far more challenging, while significant attempts to restore metabolic function through a post-mortem ex vivo perfusion of a whole brain are so rare as to be essentially unheard-of. (The most famous attempt was made by the Soviet scientist Sergei Brukhonenko, who used a circulation machine to “revive” a decapitated dog, as documented in the 1940 film “Experiments in the Revival of Organisms,” though many suspect that the footage was doctored.) “You say to a scientist that you want to do this, they’ll think you developed psychosis,” Sestan told me.
Sestan was determined to think like a scientist, not a philosopher. The existential questions interested him far less than the practical ones. “Our goal, our intention, was to do basic biology,” he told me. “And we had to be focused on what we were doing, because it was so important that everything was done correctly, that all the data was solid. When you let your imagination go berserk, when your mind wanders, you make mistakes, and one thing that I knew was that this was likely going to be the hardest thing, technically speaking, I’d ever done, and we couldn’t afford any mistakes.”
Still, as Sestan acknowledged to me, the project was an outlier for him. He felt compelled to put certain safeguards in place: He added “blockers” to the perfusate, to prevent the rise of electrical activity should the experiment succeed in restoring the neurons to do anything resembling consciousness; later, for the same reason, he began keeping a syringe full of a powerful anesthetic in his lab.
The technical hurdles were immense: To perfuse a post-mortem brain, you would have to somehow run fluid through a maze of tiny capillaries that start to clot minutes after death. Everything, from the composition of the blood substitute to the speed of the fluid flow, would have to be calibrated perfectly. In 2015, Sestan struck up an email correspondence with John L. Robertson, a veterinarian and research professor in the department of biomedical engineering at Virginia Tech. For years, Robertson had been collaborating with a North Carolina company, BioMedInnovations, or BMI, on a system known as a CaVESWave — a perfusion machine capable of keeping kidneys, hearts and livers alive outside the body for long stretches. Eventually, Robertson and BMI hoped, the machine would replace cold storage as a way to preserve organs designated for transplants.
For now, one of the few available machines — the third generation of the CaVESWave system — was in Robertson’s lab in Blacksburg, Va.; a majority of the test subjects were pig organs obtained from a nearby slaughterhouse. Sestan was intrigued, and when he traveled to the Washington area that February to present a paper on his gene-expression research, he arranged a side trip to Blacksburg to meet with Robertson in person. “I couldn’t get there fast enough,” Sestan told me. On Interstate 81, near Roanoke, he was pulled over by a state trooper. “I said: ‘I’ll be honest with you, sir. All my life, I’ve hated driving behind big trucks. They scare me. It’s my paranoia.’ ” The trooper thanked him for his honesty and wrote him a ticket anyway.
Back in New Haven, Sestan showed pictures of the machine to his colleagues. Some questioned his sanity. (“This isn’t a joke, man!” Sestan remembers one telling him.) Others, busy with their own projects, were wary of getting involved. “And that was when I found Zvonimir,” Sestan recalled. Zvonimir is Zvonimir Vrselja, a fellow Croat who was 28 at the time. Angular and bright-eyed, Vrselja specialized in radiology; he has published on the vasculature of the brain and cerebral pulsatility — the way that blood moves through the cortex. In late 2015, a colleague of Vrselja’s in Croatia reached out to Sestan and suggested that the two scientists talk. Zvonimir’s “skill set was exactly what I wanted,” Sestan told me. “Exactly.”
A few months later, Vrselja moved to New Haven; together, he and Sestan reached out to a third scientist: Stefano Daniele, a 25-year-old who had spent years researching brain degeneration in patients with Parkinson’s disease. Daniele was skeptical. In joining what was then still a top-secret project, he would have to rearrange his plans for his dual M.D.-Ph.D. degree. “Nenad took me aside,” Daniele told me, “and said: ‘I have never done anything like this; we have no data. But if it works, it’s going to change neuroscience.’ ”
In the spring of 2015, Sestan made the first of several payments on a BMI machine, which Robertson and the company estimated would take half a year to fabricate. In the meantime, Daniele and Vrselja could test out a version of the system housed at Virginia Tech. (It was decided that Sestan, with his academic commitments, would remain in New Haven.)
All three scientists were adamant that they had never once considered carrying out any tests on human specimens. The regulatory bar was too high, and as Sestan put it to me, when it comes to human tissue, post-mortem or not, “there has to be extreme justification, from an ethical standpoint. Which is exactly how it should be.” To a slightly lesser degree, the same is true of other large mammals. But dead animals are a different matter. And BMI had its relationship with the slaughterhouse near Virginia Tech. It wouldn’t be a problem, Sestan figured, to arrange for the purchase of pig brain tissue — porcine brains, after all, are usually discarded after the animal’s death.
“We knew that with a project like this one, it was going to be trial and error,” Vrselja told me. “Lots of trial and error. And to kill that number of animals, it just seemed absurd.” But if the slaughterhouse would sell them the equivalent of refuse, there would be no ethical quandary at all. “I remember we went to the slaughterhouse manager, and he shrugged. He was like, ‘Are you going to pay me?’ ” When they said they would, the manager replied, “Great, you can work out of my office.”
Almost immediately after arriving in Virginia, Vrselja and Daniele ran into a very big problem. “To perfuse something, you have to know how it works,” Vrselja recalled. “You go to an anatomy class, and that’s what you learn — how an organ functions. But there is not a lot of good literature on pig vasculature. And definitely not about how the blood circulates in a pig’s brain. We had to figure that out from scratch.”
Every morning for several weeks, the scientists woke up around 4:30 to be at the slaughterhouse as the first pigs were led to the killing floor. While they waited, the animals were stunned, killed, eviscerated and stripped of usable meat; later, Daniele and Vrselja would run carrying a bloody pig head in a bag to the manager’s office, where they would use a pump to empty the excess blood from it. Finally, placing the skull on ice, they would drive it back with them to the lab in Blacksburg.
It was difficult not to get discouraged. The architecture of the brains was only half of it: The scientists also had to learn to remove the skull in a way that preserved the organ’s vital architecture, like the arteries. And initially they were working without neurosurgical tools. “We had an oscillating saw from Home Depot,” Daniele said. “It was like sawing into the unknown, because you had to go millimeter by millimeter, and the whole key was to go as close as possible to the brain but not pierce into it, because you actually didn’t know where the floor was, where the brain was.”
With every two steps forward, they seemed to be taking another one back. By running food coloring through the arteries of the brain, Vrselja and Daniele could see how blood traveled through the organ, but the arteries split and joined at such irregular intervals that it took days to figure out how each one influenced the circulation of blood. “Every time we thought that we had it down,” Daniele told me, “a weird branch would come up and steal the circulation from the brain, and then it would leak out that way.”
By the 20th brain, they had a sense of which arteries connected to which; by the 40th, they had worked out what vessels needed to be closed off — and what sections of the skull needed to remain attached. “I remember feeling like shit, physically, because we were up at 4 every morning, going to bed at midnight and doing the same thing again,” Vrselja told me. “But eventually, there was progress.”
Sestan and his team would end up modifying nearly every aspect of BMI’s machine. Still, both the original and the current iteration, which Yale is seeking a patent for using the name BrainEx, work in fundamentally the same way. First, the brain is mostly freed from the skull; all the dangling arteries, save the carotids, are cauterized or sutured. Next, the organ is flushed of residual blood. At the same time, an amount of perfusate equivalent to a bottle of wine is brought to body temperature in the machine’s reservoir and oxygenated — as with real blood, oxygenation turns the perfusate a darker, scarlet red.
Once the fluid — the present form of which includes antibiotics and nine different types of cytoprotective agents — is ready, the brain is lowered into a plastic case the scientists have nicknamed “the football” and connected via the carotids. A small thermal unit (a miniature air-conditioner and heater) sits under the football, controlling the temperature of the organ; the pressure and speed of the perfusate, meanwhile, are governed by a type of pump. With a dull whir, the fluid begins to circulate across the arteries, capillaries and veins of the brain in a loop, exiting on each circuit through a dialysis unit that “cleans” any waste products and through a filter that removes any naturally occurring bubbles.
Perhaps the most innovative modification involved fluid mechanics, one of Vrselja’s specialties in graduate school. As the British mathematician John Womersley managed to quantify more than half a century ago, blood does not circulate through our arteries at a uniform rhythm — it circulates in pulses, in concert with the shudder of our hearts. To account for that dynamic, the BMI unit had shipped with an automated “pulse generator,” a device that replicates the heartbeat’s pulsatility in the organs.
But the pulse generator’s settings proved unsuitable for brains, which have a different flow pattern than the rest of the body. Before Sestan’s team adjusted the settings, the fluid might not completely permeate the vasculature of the organ, leaving parts of the brain essentially untreated. In such tissue, Daniele told me, “you’d end up with this sludgy, white yogurt-ish substance. It was a mess.” Conversely, if the pressure was too high, “the brain could just physically not stand it.” The organ fell apart.
By that summer, Vrselja and Daniele had fine-tuned the pulse generator and attached a number of custom sensors, which ran on software designed by Vrselja; the technology allowed them to experiment more easily, and widely, with different settings. “A good way of putting it,” Vrselja told me, “is we needed to figure out millions of years of evolution in a very short window of time.”
As the weeks went on, Vrselja and Daniele discovered something encouraging: The interior brain tissue had a moist gray hue, as a living organ would — a sign that some cellular function had been restored. But to know for sure, they would have to perform the requisite lab work.
Over the course of that spring, they fixed brains from separate specimen sets and delivered them to Sestan. “It was the most astonishing thing, ” Sestan recalls. Active brain cells can have a variety of shapes, depending on the type and function. But dead or dying or inactive brain cells tend to look alike, as if a bomb has been set off somewhere in the nucleus and the entire structure has imploded from within. In the face of almost everything that was known about the brain — in the face of centuries of scientific research — the cells from the experimental group were metabolically active. Sestan, hunched over the microscope, could hardly believe what he was seeing. “Oh, my God,” he remembers whispering to himself.
Soon, the scientists had ratcheted up the length of the perfusions, from one hour to two or three, and Sestan found himself staring down a fresh and unusual dilemma. In and of itself, he knew, cellular function is not indicative of life, just as Giovanni Aldini’s galvanic experimentation did not amount to the resurrection of an animal’s mind. And yet by all accounts, the longer Vrselja and Daniele perfused the pig brains, and the better they got at the process, the more brain cells were restored.
In 2016, Sestan employed a machine known as a BIS, or a bispectral index monitor, which is used in hospitals to measure how deeply a patient is “under” during surgery. BIS results are categorized on a scale from zero to 100: Zero is the absence of electrical activity — a chunk of wood would score a zero on the bispectral index — while 90 to 100 is consistent with full cerebral function in a living human. (A person between 40 and 60, target numbers for general anesthesia, will be unresponsive to most stimuli.)
That summer, Sestan was preparing a grant application when Vrselja and Daniele summoned him to the perfusion room. The BIS readout had just hit 10 — at the low end of what is called burst suppression, a stuttering pattern often observed in human patients in a deep coma. “That level, it’s not associated with any kind of cognition,” Daniele told me. “The brain is considered to be entirely inactive. Dead.”
And yet as low as the score was, it wasn’t zero. “I just thought, Yeah, O.K., forget it,” Sestan recalled. “I’m not taking any chances. I said: ‘Unplug the machine. Stop the experiment until we can figure out what’s happening.’ ” That same day, he wrote two emails. The first was to a contact at the National Institutes of Health. The second was to Stephen Latham, the director of the Yale Interdisciplinary Center for Bioethics.
Latham is tall and ruddy, with neatly parted gray hair and a big, gaptoothed smile. Trained as an attorney, he speaks precisely, often in complete paragraphs, as if he is weighing each word before it leaves his mouth. “I remember that I shared Nenad’s reaction, which was, ‘No, we can’t have this happening,’ ” he told me recently. “If there is even a possibility of consciousness, yeah, you have got to stop the experiment.”
Legally, Latham knew, Sestan and his team weren’t in jeopardy. “The way our existing laws on animal research work — and I’ll stipulate that these are laws that many animal ethics people take issue with — you can kill an animal,” Latham told me. “You can give an animal a disease like cancer, you can let it die and you can dissect that animal to see what happened.” Sestan hadn’t killed any animals; he had merely recycled flesh that would have otherwise been disposed of. “Nenad wasn’t even at the boundary of what isn’t permissible,” Latham said.
And yet in another way, Sestan had long since passed any known boundaries. Cellularly revived dead tissue is “an in-between category,” said Nita Farahany, a law scholar and ethicist at Duke University. “It’s a total gray zone.” There were no rules in place to follow, and no rules to break.
For Sestan, the thorniest issue centered on consciousness and whether the Yale team, inadvertently, might somehow have figured out a way to elicit it from dead flesh. In 2019, brain death — and thus complete loss of consciousness — has become something of a moving target: Research has shown that patients we once thought were in deep comas as a result of a traumatic brain injury are actually able to communicate. As Christof Koch, the neuroscientist, writes, all neurologists agree that electricity in the brain is a prerequisite for thought. But new technologies, including a machine nicknamed the “zip-and-zap,” which uses both EEG monitoring and transcranial magnetic stimulation, have been used to detect brain activity in patients assumed to be in a vegetative state. These machines, Koch writes, challenge “clinicians to devise more sophisticated physiological and behavioral measures to detect the faint telltale signs of a mind.”
As Sestan knew, the chances of real consciousness arising from the perfused brains were slim, thanks to the channel blockers. But there was a worst-case scenario: A partly revived post-mortem brain, trapped in a feverish nightmare, perpetually reliving the very moment of its slaughter. “Imagine the ultimate sensory-deprivation tank,” a member of the N.I.H.’s Neuroethics Working Group told me. “No inputs. No outputs. In your brain, nobody can hear you scream.”
In August, with the experiment now paused, Sestan and his team went to Washington to meet with the members of the N.I.H.’s working group. “It’s fair to say that we were shocked,” the member told me this spring. “Astounded, I suppose.”
The board suggested that Sestan trade in the BIS monitor, which is not made for nonhuman subjects, for a more sensitive electrical monitoring system. And a colleague gave him a name: Rafeed Alkawadri, an expert in invasive intracranial EEG evaluations — a form of electrocorticography, or ECoG, in which the electrodes are connected directly to the brain’s surface rather than the exterior of the head. “Electrocorticography was the way to go, but with ECoG, generally speaking, you’ve got a scalp,” Sestan recalled. “With our experiment, we had no scalp. We said, ‘Let’s get this equipment into the lab.’ ”
A few days later, Alkawadri completed a round of tests on a perfused porcine brain. He saw no “spontaneous global activity” present in the organ or communication between the various parts of the brain; the BIS reading of 10, Alkawadri theorized, was a result of electrical interference produced by the machine.
Still, the incident was not exactly a false alarm. Sestan considered it more like a warning. Remove the channel blockers, he told me, “and you might get a signal” — a real one. I wondered if he had thought about trying it. “No,” he answered quickly. “Not now. And just speaking for myself here, maybe not ever.”
By early 2017, Daniele and Vrselja were again expanding the length of the perfusions, past three hours and then to four. But the brains in the control group couldn’t survive cellularly past 240 minutes, at which point decomposition set in, making comparison to the experimental group impossible beyond that.
After the N.I.H. meeting, Sestan was invited to Duke University to speak with the members of the school’s bioethics faculty and others. “People were aghast,” one person familiar with the meeting told me, “because everyone had this image of a pig’s head on a lab cart, attached to a bunch of hoses and tube, and the pig’s head coming back to life. There was a lot of concern,” the person went on, “that if this was to be made public in the wrong way, it could really be a setback for brain research. Like, decades of setback. It was so easily caricaturized.”
That summer, after a source told me about the Duke meeting, I reached out to Sestan. In a phone call, he called the experiment “the most important thing I’ve ever done, and the most important thing I will ever do,” and mentioned he was preparing to submit a paper to Nature. Once it had been accepted, he went on, he would get back in touch with me; until then, he wasn’t able to comment on the record.
In March 2018, Sestan met again with the N.I.H. Under the impression that everything he said would be kept confidential, he had put together a presentation on his experiment, and while the dozen or so attendees looked on, he clicked through a series of slides showing restored cells from the perfused brains. According to later reports, Sestan, referring to the most recent ECoG data, stressed that he was confident that the brains in his experiment were “not aware of anything.” Still, he went on, he could not speak to what other scientists might do with the research. “Hypothetically, somebody takes this technology, makes it better and restores someone’s [brain] activity,” he said. “That is restoring a human being. If that person has memory, I would be freaking out completely.”
With each meeting, the number of people aware of the project was growing, and Sestan, despite what he described to me as “begging and pleading,” was unable to prevent the publication last spring of an article in the MIT Technology Review, which was apparently based on video of Sestan’s 2018 N.I.H. presentation. Published with a still of a scene from the Steve Martin comedy “The Man With Two Brains,” the article framed Sestan’s work as “a step that could change the definition of death” — a “feat” that “inaugurates a bizarre new possibility in life extension.”
Within hours, the news had been picked up by media outlets around the world. “Scientists keeping pig brains ‘alive’ inside their SEVERED heads in Frankenstein-style research,” read the headline in the British tabloid The Mirror. The conspiracy theorist Alex Jones brought up the experiment on his radio show.
The email flooded in to Sestan’s office. “In case a study comes up and I find myself dying at that time, I volunteer for the brain study,” one read. “That’s right, I give you permission to, upon my untimely death, extract my brain and keep it ‘alive’ as long as you can outside the context of my body.” Another writer chided Sestan for taking measures to prevent the emergence of consciousness. “Progress cannot and should not be held back. ... I suggest you seek private research funding from Silicon Valley, there is many a great powers and influential men who would fund this line of research and see it through to its full potential.” Finally, and most tragic, there were the relatives of patients who suffered brain trauma. What Sestan’s project proved, a mother in New England wrote hopefully, was that “there is no way to know when someone is truly dead.” Sestan told me: “You want to respond to each email, you want to try to explain the science, but you can’t. There are just too many.”
This spring, I flew to New Haven to tour Sestan’s lab. In a show of ceremony, he saved a viewing of the BrainEx for last. “You,” he said proudly, throwing open the door to a converted supply closet, “are the first member of the public to see it.” Roughly eight feet wide and mounted on the shelves of a long metal hospital-style cart, the BrainEx was less a single machine than a bristling collection of individual machines, each connected to the next, in a simulacrum of the human body. Here, the pulse generator — the equivalent of a heart. Here, the filters — mechanized kidneys. There, the device that, like lungs, helped oxygenate the perfusate. “We’ll do our dance,” Daniele said, and he commenced a dry run — sans brain — of the process, miming each step.
“Don’t forget the Kanye,” Daniele joked.
“Our soundtrack,” Vrselja said with a grin.
By any measure, the contents of the paper Sestan and his team published in Nature this April were astonishing: Not only were Sestan and his team eventually able to maintain perfusion for six hours in the organs, but they managed to restore full metabolic function in most of the brain — the cells in the dead pig brains took oxygen and glucose and converted them into metabolites like carbon dioxide that are essential to life. “These findings,” the scientists write, “show that, with the appropriate interventions, the large mammalian brain retains an underappreciated capacity for normothermic restoration of microcirculation and certain molecular and cellular functions multiple hours after circulatory arrest.”
When we spoke in June, shortly before this article went to press, Sestan told me he frequently marveled at the direction the experiment had ultimately taken. “You know, I started out hoping to be able to trace connections,” he said. “But in the last three years, what happened was that the project really became more about death than anything having to do with the connectome.”
“The whole project is testament to the fact that the simplest observations can lead to the most exciting findings,” said Stephen L. Hauser, director of the Weill Institute for Neurosciences at the University of California, San Francisco. “It’s the type of finding that after it is made, it might seem obvious. One reaction could be, ‘Hey, why didn’t we think of that?’ But it took creativity, it took doggedness to get to that point.”
In our conversations, Sestan was always happy to expound on the science behind his experiment but cagier when it came to the implications. In the field of modern neurology, Hauser told me, “you’re constantly trying to dampen down overinterpretation. Often, that’s easy, because what’s being written about it is an incremental change over what’s already been established, or it’s just total baloney. Here, though, with this paper, we have something different: These are truly superb scientists. I think there’s a lot more that we still have to learn; the story’s not yet complete. But this is interesting, real science.”
Sestan did acknowledge that, yes, theoretically there is nothing stopping a scientist from immediately building a perfusion machine that could support a human brain. The BrainEx technology is open-source, and pig and homo sapiens brains have a fair amount in common. And there are plenty of conceivable applications for a human-optimized BrainEx. In addition to being an ideal model for testing out drugs, a portable perfusion system might be used on the battlefield, to protect the brain of a soldier whose body has been grievously injured; it might, in some distant future, become standard equipment for first responders. “The thing is,” Sestan said, “there’s a lot of research left to be done.” His focus now is better understanding how brain cells can be saved after major heart events. He sees no path to human tests. “If you could be absolutely certain you could do this on a post-mortem human brain and not get electrical activity of any kind, then maybe, maybe, we talk more,” he went on. “At the moment, I can’t see justification.”
And yet, as the ethicist and Stanford University law professor Hank Greely argued to me recently, we live in a time of breakneck scientific advancements; in 2019, “what ifs” advance more rapidly to the experimentation stage than ever before. Consider, Greely suggested, the case of the Italian neurosurgeon Sergio Canavero and his associate, the Chinese scientist Xiaoping Ren, who claim to have transplanted a head from one cadaver to another. Undoubtedly, a scientist with fewer scruples than Sestan, fewer moral qualms about human experimentation, will emerge. “Somebody will perfuse a dead human brain, and I think it will be in an unconventional setting, not necessarily in a pure research manner,” Greely told me. “It will be somebody with a lot of money, and he’ll find a scientist willing to do it.”
Greely and Nita Farahany of Duke, along with the young Duke scientist Charles M. Giattino, recently published a long essay in Nature on Sestan’s findings. (Their 2,000-word essay is one of two to appear alongside the paper.) “In our view, new guidelines are needed for studies involving the preservation or restoration of whole brains,” they wrote, “because animals used for such research could end up in a gray area — not alive, but not completely dead.” They noted, “We’re reminded of a line from the 1987 film ‘The Princess Bride’: ‘There’s a big difference between mostly dead and all dead. Mostly dead is slightly alive.’ ”
In the paper, Greely, Farahany and Giattino advocate the adoption of guidelines modeled on those established in 2005 on stem-cell usage. “Looking back, those guidelines really helped shape the field,” Greely told me. “Here, we have nothing. We have serious gaps in the regulatory system. We need to be proactive.”
Sestan, for his part, agrees. “Every one of these decisions,” he told me before I left New Haven, “shouldn’t be up to me alone.” In solving countless technical problems, he knew, he had created an entirely new set of implications for the rest of us to wrestle with. “I shouldn’t decide,” he went on, “what we do or what we shouldn’t do. That’s up to you; it’s up to all of us. We make the decision together.”