Part 5 (1/2)

Then we have that mournful scholar dreaming of his lost Lenore, and the bird that croaks from the bust of Pallas just above his chamber door: ”Take thy beak from out my heart, and take thy form from off my door!”Quoth the Raven, ”Nevermore.”

In any case, it's a simple point. If life is a chain with seven weak links, then you have to fix each and every one of those weak links to strengthen the chain.

Aubrey's suggestion about moving those vulnerable thirteen genes out of the mitochondria was intriguing. I've since talked about it with a number of biologists. All of them thought it was ridiculously complicated and risky, but a few found it interesting, even so. One famous molecular biologist, Seymour Benzer, at Cal Tech, who had taken up the study of mortality in his old age, told me that he and a student had tried to make the repairs that Aubrey was suggesting, in fruit flies, one summer. They ran into a few technical difficulties and he set the experiment aside.

Aubrey went on with his list. First, we have the cross-links that wrinkle our skins and stiffen our veins and arteries and do all kinds of visible and invisible damage to our bodies as we get older. Second, we have the mutations that acc.u.mulate in our mitochondria. Third, we have junk that acc.u.mulates inside the nerve cells of our brains. Whenever pathologists autopsy the brains of people who have died of Parkinson's, they find Lewy bodies, for instance, which are tiny b.a.l.l.s of nasty protein.

These clumps and b.a.l.l.s are hydrophobic; so we talked a little more about hydrophobicity, and its importance in the life of the cell. All of our molecular machinery in the cell is made of proteins, and when the cell manufactures proteins, they extrude from the cells' manufacturing sites like long straight noodles of pasta. After these long spaghetti noodles are extruded they fold up almost instantly into complicated and intricate shapes. Their shapes, if they were entered into contests, would win every prize on Earth for architectural, industrial, and sculptural design. It's as if you dropped the noodles into the pot and they did not just cook until they were al dente al dente; one of them folded up, in a time much less than the blink of an eye, into a machine that dices, and another into a machine that chops, and another into a machine that blends. And the tiniest differences in these designs can become matters of life and death as we get older. For instance, in some families, people tend to develop Alzheimer's disease very early, in their forties and fifties. They have the bad luck to carry mutations in their genes for beta-amyloid. The mutations make their beta-amyloid more hydrophobic. So it's more likely to clump in their cells. According to present thinking, if beta-amyloid clumps in your skin cells, it may not do much harm. But if it clumps in the nerve cells in your brains, it can do terrible harm, because those cells are so delicate, complicated, and crucial to our functioning as human beings. Michael Hecht, a chemist at Princeton University, is in the middle of a series of experiments in which he inserts various versions of beta-amyloid into bacteria to see if they clump and aggregate. He rigs the experiments so that if the beta-amyloid folds up properly, it lights up and fluoresces a bright green. But if the stuff clumps and aggregates in the cells, it doesn't light up. Again, it's all just simple cooking combined with simple engineering, but at the level of molecules instead of noodles and oil in a pot. Hecht makes random changes in the beta-amyloid and finds that those changes that make it more hydrophobic do make it tend to clump more. The fatal differences are subtle. A basic protein is shaped like a noodle with lots of little attachments called ”side chains.” If you have all those side chains in the right place, you may live past the age of one hundred with all your wits and memories. But if just one side chain is in the wrong place, your whole family is in danger of developing Alzheimer's in early middle age.

Sitting in my study, Aubrey reviewed the issue of the junk in the brain cells. No one knows how much damage this debris does to the brain and to the life of the mind. No one knows if or how they cause Alzheimer's and other dementias. We really don't know much about dementia, which is not surprising, because we don't know much about how brains produce consciousness. If we knew how the brain makes the mind, it might be easier to figure out why the brain stops making the mind. If we knew how the body makes the mind, we might be able to figure out how a sick body makes a sick mind. Meanwhile the study of Alzheimer's and other dementias is a huge, growing field, and the various schools of thought clash like ignorant armies. Some neurologists think the worst kind of junk in there is the beta-amyloid protein, or BAP; other neurologists blame the tangles, which are made of a protein called tau. These two camps call themselves the Baptists and the Tauists. Battles are fought between the Baptists and the Tauists. It's a small war; but even so, feelings run high.

While Aubrey was telling me his plans to clear away the junk from old brain cells, I heard my wife's steps hurrying up the stairs to my study. She poked her head in the door to tell me some news about a friend of ours. By a strange coincidence, the news had to do with Alzheimer's. Our friend's elderly mother had just been found wandering in a town half an hour from ours. Our friend was at work far away, and she had gotten a call from the police. She needed my wife to go fetch her mother from the station.

After my wife drove off, Aubrey returned to the battles of the Baptists and the Tauists. Each side had its points. ”But I don't need to care about that,” Aubrey said. ”I take the view, no matter what the change is between young and old, if you fix everything, then-”

Just fix every weak link in the chain.

It had taken us a few hours to talk through just three of Aubrey's Seven Deadly Things: cross-links, mitochondrial mutations, and the junk that builds up between nerve cells. Three down, four to go. Aubrey seemed to feel more encouraged than discouraged as he laid all this out. Part of the beauty of his plan in his view was that you didn't need to settle the war between the Baptists and the Tauists, or any other controversy in science and medicine. The thing for us to do is to get rid of all the junk that acc.u.mulates in aging bodies. ”I just want to fix everything unless I'm completely convinced it's not in the killer camp.”

So that famous night before dawn in his motel room in California, Aubrey had scribbled them all down on a sheet of paper, the basic kinds of detritus that acc.u.mulate. The list itself was a bit confusing back then. In no particular order, here is one tidy way to sum it up: There's junk inside cells; and there's junk outside cells. There are mutations inside the nucleus; and there are mutations outside the nucleus. There are too few cells; there are too many cells. And there are the cross-links, which stiffen up our working parts everywhere throughout the body at the finest scale. Aubrey had to come up with strategies to fix each one of these Seven Deadly Things. These are the plans that he soon came to call his Strategies for the Engineering of Negligible Senescence, or SENS.

It's a provisional list, of course. Again, the manifold damage we call aging is like the Hydra. If we lop and burn off one head of the monster, the others remain our mortal enemies, and they will bring us down. Most doctors and medical researchers have made their peace with this. They'd be content to solve just a piece of the problem of mortality. If they succeed in treating arthritis or curing Alzheimer's they will slow aging by some small amount. Like inventors and innovators throughout modern history, they will give us the gift of a few more minutes, hours, days, a few years at the most. But immortalists like Aubrey de Grey don't want to slow aging, they want to kill it. To do that, they have to win a war on every front at once. They have to lop off every last head of the Hydra. It would be a labor of Hercules to lop them all off. But we could do it, Aubrey says. And he would be willing to add another to the list if it reared its ugly head.

After half a day of talking with Aubrey, I wasn't sure what to make of him. He did seem enormously well-informed. And he had credentials. He'd hosted an international meeting of gerontologists in Cambridge under the banner of SENS. ”They gave me a standing ovation at the end of the meeting,” Aubrey told me. ”And I'll have to do it again, which suits me fine.” And he'd arranged special, smaller meetings of experts to talk about some of his ideas for fixing the Seven Deadly Things.

On the other hand, it all did sound a little crazy. Darwin's mentor, the geologist Charles Lyell, advised him to avoid controversy it's a terrible waste of time. When you follow the edges and frontiers of science, you try to watch where you step. It's only too easy to waste years in controversy, or step right over the edge. A man with a bottomless bottle of beer, and a beard halfway down to the floor, who claims we can live a thousand years, presents a picture that more or less defines the realms beyond the edge of science, like those sea serpents in the old maps with the legend ”Here be dragons.”

From my bookshelf, I took down my copy of Bacon's History of Life and Death History of Life and Death. I read aloud the pa.s.sage where Bacon explains why we should in theory be able to live forever: ”for all things in living creatures are in their youth repaired entirely; nay, they are for a time increased in quant.i.ty, bettered in quality.” So much so that ”the matter of reparation might be eternal, if the manner of reparation did not fail.”

I thought Aubrey would agree with Bacon, but he shook his head. ”That can no longer be sustained,” he said. ”It is true if you don't get down into too much microscopic detail. We see no decline in function of tissues until middle age. But the things that cause decline started in conception-or even before, you could argue, in the unfertilized egg. Certainly in prenatal life.” Even in the tissues in an embryo, or the cells in a single tissue, slight errors are being made from one reproductive cycle to the next. When cells divide, the changes get pa.s.sed down. That is one reason that identical twins are never really identical. You could say that junk is already building up in the first moments of the life of the fertilized egg.

”What's going on during early life is a gradual laying down of damage,” Aubrey said. ”All the same things I've been talking about happen all through life. I'll try to say it concisely,” he said, rapping his palms on his thighs. ”A forty-year-old is different in composition from a twenty-year-old. In what way way is that person different? There are no easy answers. The differences are very subtle, very slight. But you know they're significant because the forty-year-old has a life expectancy that's twenty years shorter than the twenty-year-old.” Whatever your age, and wherever on Earth you live, your mortality rate doubles every eight years or so, from birth to death. And it doubles because of the buildup of damage and garbage. is that person different? There are no easy answers. The differences are very subtle, very slight. But you know they're significant because the forty-year-old has a life expectancy that's twenty years shorter than the twenty-year-old.” Whatever your age, and wherever on Earth you live, your mortality rate doubles every eight years or so, from birth to death. And it doubles because of the buildup of damage and garbage.

Every gerontologist knows about this doubling of mortality rates. This is one way to measure aging: the likelihood of dying at each age. Actuaries call it the ”law of mortality.” The mortality rate of a man of fifty is many times greater than the mortality rate of a boy at fifteen. In fact, our mortality rates-over most of the world-double every eight years or so. This is a puzzle: Why should the doubling rate be the same around the world when local populations have such different risks-for instance, low risk of breast cancer in j.a.pan, a tenth what it is in the United States? As a proponent of the theory of the Garbage Catastrophe, Aubrey argues that the rates are so uniform around the world because so many different kinds of junk build up in our bodies wherever we live on the planet.

”So what's going on during early life is a gradual laying down of damage,” Aubrey said. We already have the start of atherosclerotic plaques in our major arteries and cross-links in our skin as toddlers.

”All the things I've been talking about happen all through life. The only reason it looked to Bacon as just described is that those types of damage, until they reach a threshold, a certain level of abundance-” Until we are thirty or forty, Aubrey said, the damage is too insignificant to matter. ”Until then it looks like there's no aging going on.”

That really is a sensible description of aging, according to present thinking. Unfortunately, I thought, Aubrey's prescriptions were carefully posed to sound more sensible and plausible than they might to skeptics who are aware of the trade-offs involved. Stimulating the immune system can be dangerous, for instance. The body develops inflammation to try to disperse a foreign body or kill it. And it is usually very effective; but the downside is that cells do it by releasing oxidants, and that's bad. So acute inflammation can be healthy, but chronic inflammation is not. That is why Caleb Finch, of the Andrus Gerontology Center at the University of Southern California, Los Angeles, argues that inflammation may be a crucial problem in aging itself.

But Aubrey had his stump speech about the Seven Deadly Things and he stayed right on that stump. Acc.u.mulating damage drives our cells more or less crazy, Aubrey writes in Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime, by Aubrey de Grey, Ph.D., with Michael Rae. (On the back jacket, in big capital letters: ”PEOPLE ALIVE TODAY COULD LIVE TO BE A THOUSAND YEARS OLD. A LEADING RESEARCHER SKETCHES THE REAL 'FOUNTAIN OF YOUTH.'”) The damage, he writes, ”forces our cells to flail about in increasingly desperate, disorderly, and panicked attempts to keep their heads above the waters of the aging process.” The way to keep the forty-year-old's life expectancy the same as the twenty-year-old's is to keep cleaning up all of that detritus, by stimulating the immune system, etcetera. And we don't have to clean up everything that will ever matter to the aging body; only those insults that matter within our life spans now-only those things that slow us down in threescore years and ten. ”Once this is accomplished,” Aubrey writes, ”our bodies will remain youthful during the years in which they are now undergoing a slow descent into decrepitude.” So we will try to stay young and fit while we wait for more help from science, the way other generations strove to stay virtuous while they waited for the Messiah.

Once we did it, once we fixed all seven weak links, eliminated all of Aubrey's Seven Deadly Things, we would live long enough at last to achieve ”escape velocity.” We would live virtually forever. We would have achieved negligible senescence. At that point human life would be completely transformed, of course. Among other things, virtually everyone on this planet would feel as Aubrey did, that there was little point in having children, because there was so much to do. Each of us would feel that we had so much life ahead to enjoy just for ourselves.

”We'd have no one under the age of fifty soon enough,” he said cheerfully.

I went down to the refrigerator with Aubrey to get him another bottle of beer, and we ran into my two boys. They were fourteen and seventeen years old, and they were curious about him. You don't meet many characters like Aubrey de Grey in small-town Pennsylvania.

Aubrey was wound or overwound, singing his long saga of the Seven Deadly Things, and he went straight back to the top when he saw my boys.

”Suppose we fix aging,” Aubrey told them in the kitchen. ”So your risk of death is postponed indefinitely. You'd live in the region of a thousand years. You You have a better chance than have a better chance than you you, and you you have a better chance than have a better chance than you you,” Aubrey said, pointing with his right hand to each one of us in order of age, from the youngest to the oldest (me), while he squirreled his left hand deep into his beard.

”But once we have learned to postpone senescence indefinitely, our life span will become limited only by accidents, and that will give us an average life expectancy of one thousand years. So people are likely to live a long, long time,” he said. ”It seems extremely plausible to me that by then you'd live long enough to live essentially indefinitely.”

My boys, both of them science-fiction fans, seemed comfortable with Aubrey's confidence that they would live indefinitely. One of them mentioned Star Trek Star Trek teleportation. ”Beam me up.” The beam from the s.p.a.ces.h.i.+p lifts the astronaut from here to there, sometimes thousands of miles away, or more-but maintains the same person. teleportation. ”Beam me up.” The beam from the s.p.a.ces.h.i.+p lifts the astronaut from here to there, sometimes thousands of miles away, or more-but maintains the same person.

”Yes,” said Aubrey. ”That is fast teleportation. This is slow teleportation. You'd be maintaining the same person from century to century by medical means. And if you suffered an accident, eventually we'd know enough to put you back together again no matter what happened.”

I protested. We don't know how the brain works. What about the brain, the mind, ident.i.ty? Aubrey replied that there was no way of knowing what exactly the doctors would have to transfer into the reconstructed brain to make sure that ident.i.ty is carried over. But in practice he was sure the doctors of the future would be able to do it.

I gave Aubrey another look.

We can't do anything like that now, he conceded. ”But it's not implausible for, say, one hundred years from now.” To make a map of your patient you'd scan the brain. Then you'd have all the information you'd need to re-create your patient in case of an accident. ”Not obvious you could not not do it.” He found such scans perfectly easy to imagine. You'd get one every month. Then if you came to some sticky end, your doctor would use the last scan to reconstruct you. Beam you up. Restore you, and restore your memory files. You wouldn't lose one bit. do it.” He found such scans perfectly easy to imagine. You'd get one every month. Then if you came to some sticky end, your doctor would use the last scan to reconstruct you. Beam you up. Restore you, and restore your memory files. You wouldn't lose one bit.

Aubrey went on, with the same sort of pleasure with which he'd just been talking about clearing away the junk from aging brains. ”Well,” he said, ”would you really be the same person that went under the truck? I've tried to think subjectively: What is my emotional attachment to the body that went to sleep in O'Hare last night?” He said he was perfectly able to reestablish a sense of continuity after sleep. Why not after a scan? ”I think it's very likely.”

All this is far in the future, I cautioned my boys. We don't know how to begin to do this now.

Aubrey agreed. But we don't have to worry about any of that today, he said. We are still very attached to our bodies. He used the phrase ”meat puppets.” We want to keep our meat puppets. If we achieve immortality by uploading our minds into supercomputers, then we will have to say goodbye to our bodies, our meat puppets, forever. ”So, not uploading,” Aubrey said. ”I'll stick with the meat-puppet approach. Of course, if you live a thousand years, driving will be outlawed! It could be a highly risk-averse world.” Here he returned to his theme in my car on the way from the airport. If you hope to live a thousand years and you are struck by a cab at twenty-five, you lose an awful lot. ”That would p.i.s.s people off. So there will be an incentive to improve medical care-traditional medical care. And there will be all kinds of safety precautions. Climb a mountain, they'll catch you before you hit the ground if you fall. Automated cosseting. But of course there's only so far you can go. Like how many people you could have s.e.x with without catching something.” My boys looked impressed that Aubrey was talking so freely in front of them.

I asked him how long he thought it might be before we arrive at this automated, cosseted world.

”I wouldn't be surprised if it's here in a hundred years,” he replied. ”I plan to be around. I will warn you that I was surer of that ten years ago than I am now. I feel it's all very well to take this view selfishly. But ultimately if I can do something to add even one day to the human life span...”

Here he went into his statistical rap. Already this was the third or fourth time I'd heard it. He was beginning to remind me of a wound-up clock that chimes on the hour, or a salesman who makes the same speeches so often that he forgets what he's just said to you and lives in mortal danger of repeating the same anecdotes two or three times in one pitch. He explained about escape velocity, and saving one hundred thousand lives a day.

While Aubrey talked, I tried to read my boys' faces. No, they did not seem shocked by his confidence that they would live forever. They took their immortality for granted. If anything, I thought they seemed happy to meet an adult who was willing to acknowledge the truth. They told me later on that they thought Aubrey's argument was sensible. He seemed very full of himself, but his premise was only common sense. One of them told me, ”I think he is knurd. He is excessively sober.” My son had gotten the word from Sourcery Sourcery, a science-fiction novel by Terry Pratchett. ”Knurd” is ”drunk” spelled backward. Pratchett writes, ”Knurdness strips away all illusion, all the comforting pink fog in which people normally spend their lives, and lets them see and think clearly for the first time ever. Then, after they've screamed a bit, they make sure that they never get knurd again.”

For his part, when we were back in my study over the garage, Aubrey told me that he found it refres.h.i.+ng to talk about immortality with teenagers. They are people who are positive and adventurous about the future. He feels frustrated when he talks with those who are less adventurous. ”That means nearly everybody in influence and power,” he says. ”Middle-aged and older. They find it so shocking that we might create a world so different from the world they're used to. They're very resistant to even thinking about the desirability of it-that it might be a good thing. People are like that. There's only so much change they can think about. I'm guilty of this myself. Young people talk about uploading. One of your sons brought this up. I just can't see it-can't see it being useful. It seems in no way desirable. But that may be a danger of being over thirty.”

Of course, we were getting ahead of ourselves. There were really two enormous questions to discuss: feasibility and desirability. As philosophers say, ”can” is not the same as ”ought.” Aubrey and I agreed that we would save ”ought” for another conversation.

I felt sure that the answer to the first question was no no. The conquest of aging was impossible. The point that bothered me most in Aubrey's spiel was his a.s.sumption that we could understand the machinery of our bodies well enough to clean them up. ”But we don't have to understand metabolism,” he insisted, once again. ”I say, go in early enough but also late enough. Early enough to help, but late enough so that you are out of the way of the really complicated stuff.”

He saw himself as working in the tradition of the theoretical biologists. ”Theoretical biology has an incredibly bad name,” he said. ”And the reason it's got a bad name is well understood. Since we deal with such complicated systems, biology is a big big subject, and it's very easy if you're an amateur to read a bunch of literature and come up with a nice hypothesis to explain all this data; and if you're careless, you tend to rush into print without checking to see if your idea is consistent with the other 99 percent of data that you haven't got around to reading. This has happened a lot. That's how theoretical biology got into the fix it's in today.