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Thursday, September 22, 2011

UC San Diego biologists discover genes that repair nerves after injury

Biologists at the University of California, San Diego have identified more than 70 genes that play a role in regenerating nerves after injury, providing biomedical researchers with a valuable set of genetic leads for use in developing therapies to repair spinal cord injuries and other common kinds of nerve damage such as stroke.

While scientists in recent decades have gained a good understanding of how nerve cells, or neurons, develop their connections in the developing embryo, much less is known about how adult animals and humans repair — or fail to repair — those connections when axons are damaged.

Of particular interest to the UC San Diego biologists are six genes that appear to repress the growth of axons. The scientists were also surprised to learn that some of the genes they found to be involved in the re-growth of axons were known to have other functions, such as regulating the release of neurotransmitters.

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Global Source and/or and/or more resources and/or read more: http://goo.gl/JujXk ─ Publisher and/or Author and/or Managing Editor:__Andres Agostini ─ @Futuretronium at Twitter! Futuretronium Book at http://goo.gl/JujXk
 Scientists turn back the clock on adult stem cells aging

Researchers led by the Buck Institute for Research on Aging and the Georgia Institute of Technology have shown they can reverse the aging process for human adult stem cells, which are responsible for helping old or damaged tissues regenerate. The findings could lead to medical treatments that may repair a host of ailments that occur because of tissue damage as people age.

“We demonstrated that we were able to reverse the process of aging for human adult stem cells by intervening with the activity of non-protein coding RNAs originated from genomic regions once dismissed as non-functional ‘genomic junk’,” said Victoria Lunyak, associate professor at the Buck Institute for Research on Aging.

Adult stem cells are important because they help keep human tissues healthy by replacing cells that have gotten old or damaged. They’re also multipotent, which means that an adult stem cell can grow and replace any number of body cells in the tissue or organ they belong to. However, just as the cells in the liver, or any other organ, can get damaged over time, adult stem cells undergo age-related damage. And when this happens, the body can’t replace damaged tissue as well as it once could, leading to a host of diseases and conditions.

But if scientists can find a way to keep these adult stem cells young, they could possibly use these cells to repair damaged heart tissue after a heart attack; heal wounds; correct metabolic syndromes; produce insulin for patients with type 1 diabetes; cure arthritis and osteoporosis and regenerate bone.

The team began by hypothesizing that DNA damage in the genome of adult stem cells would look very different from age-related damage occurring in regular body cells. They thought so because body cells are known to experience a shortening of the caps found at the ends of chromosomes, known as telomeres. But adult stem cells are known to maintain their telomeres. Much of the damage in aging is widely thought to be a result of losing telomeres. So there must be different mechanisms at play that are key to explaining how aging occurs in these adult stem cells, they thought.

Researchers used adult stem cells from humans and combined experimental techniques with computational approaches to study the changes in the genome associated with aging. They compared freshly isolated human adult stem cells from young individuals, which can self-renew, to cells from the same individuals that were subjected to prolonged passaging in culture. This accelerated model of adult stem cell aging exhausts the regenerative capacity of the adult stem cells. Researchers looked at the changes in genomic sites that accumulate DNA damage in both groups.

“We found the majority of DNA damage and associated chromatin changes that occurred with adult stem cell aging were due to parts of the genome known as retrotransposons,” said King Jordan, associate professor in the School of Biology at Georgia Tech.

“Retroransposons were previously thought to be non-functional and were even labeled as ‘junk DNA’, but accumulating evidence indicates these elements play an important role in genome regulation,” he added.

While the young adult stem cells were able to suppress transcriptional activity of these genomic elements and deal with the damage to the DNA, older adult stem cells were not able to scavenge this transcription. New discovery suggests that this event is deleterious for the regenerative ability of stem cells and triggers a process known as cellular senescence.

“By suppressing the accumulation of toxic transcripts from retrotransposons, we were able to reverse the process of human adult stem cell aging in culture,” said Lunyak.

“Furthermore, by rewinding the cellular clock in this way, we were not only able to rejuvenate ‘aged’ human stem cells, but to our surprise we were able to reset them to an earlier developmental stage, by up-regulating the “pluripotency factors” — the proteins that are critically involved in the self-renewal of undifferentiated embryonic stem cells.” she said.

Next the team plans to use further analysis to validate the extent to which the rejuvenated stem cells may be suitable for clinical tissue regenerative applications.

Read more: http://goo.gl/oeKIB

Global Source and/or and/or more resources and/or read more: http://goo.gl/JujXk ─ Publisher and/or Author and/or Managing Editor:__Andres Agostini ─ @Futuretronium at Twitter! Futuretronium Book at http://goo.gl/JujXk
 Electrical stimulation of brain boosts birth of new cells

Stimulating a specific region of the brain leads to the production of new brain cells that enhance memory, researchers at The Hospital for Sick Children have found. The findings show how deep brain stimulation (DBS) — a clinical intervention that delivers electrical pulses to targeted areas of the brain — may work to improve cognition.

“DBS has been quite effective for the treatment of movement disorders, such as Parkinson’s disease, and has recently been explored for treatment of a range of neurologic and psychiatric conditions,” said Paul Frankland, PhD, senior author of the study. “These new findings have important clinical implications as they inform potential treatments for humans with memory disorders.”

Throughout life, new cells are born in parts of the hippocampus, the brain’s learning and memory center. In the new study, Frankland and his colleagues found that one hour of electrical stimulation to the entorhinal cortex — a region that directly communicates with the hippocampus — in adult mice led to a two-fold increase in new cells in the hippocampus. Although the burst of new cells lasted for only about one week, the cells produced during this time window developed normally and made connections with other nearby brain cells.

Six weeks later, the researchers evaluated whether the newly integrated cells produced changes in memory. The authors tested how well the animals learned to navigate onto a landing submerged in a small pool of water. Compared with mice that did not receive the therapy, DBS mice spent more time swimming near the landing, suggesting that stimulation of the entorhinal cortex improved spatial learning.

In a related preliminary study, researchers led by Andres Lozano, MD, PhD, of Toronto Western Hospital, recently published a Phase I clinical trial showing that DBS of the fornix, a brain region that also communicates directly with the hippocampus, slows cognitive decline in some people with dementia and other cognitive impairments. “The pro-cognitive effects of deep brain stimulation in human patients may result from the production of new neurons,” Frankland said.

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Global Source and/or and/or more resources and/or read more: http://goo.gl/JujXk ─ Publisher and/or Author and/or Managing Editor:__Andres Agostini ─ @Futuretronium at Twitter! Futuretronium Book at http://goo.gl/JujXk
 Marijuana could prevent post-traumatic stress symptoms

Administering cannabinoids (synthetic marijuana) after experiencing a traumatic event blocks the development of post-traumatic stress disorder symptoms in rats, according to a new study conducted at the University of Haifa.

The researchers exposed a group of rats to extreme stress. The rats displayed symptoms resembling PTSD in humans, such as an enhanced startle reflex, impaired extinction learning, and disruption of the negative feedback cycle of the stress-influenced HPA axis.

A week later, the researchers examined the rats and found that the group that had not been administered marijuana and the group that got the injection 48 hours after experiencing trauma continued to display PTSD symptoms as well as a high level of anxiety. By contrast, the PTSD symptoms disappeared in the rats that were given marijuana 2 or 24 hours after experiencing trauma, even though these rats had also developed a high level of anxiety.

“This indicates that the marijuana did not erase the experience of the trauma, but that it specifically prevented the development of post-trauma symptoms,” said Dr. Akirav of the University of Haifa’s Department of Psychology, who added that the results suggest there is a particular window of time during which administering marijuana is effective. Because the human life span is significantly longer than that of rats, Dr. Akirav explained, one could assume that this window of time would be longer for humans.

The second stage of the study sought to understand the brain mechanism that is put into operation during the administering of marijuana. After the trauma, they injected the synthetic marijuana directly into the amygdala area of the brain, the area known to be responsible for response to trauma. The researchers found that the marijuana blocked development of PTSD symptoms in these cases as well. From this the researchers were able to conclude that the effect of the marijuana is mediated by a CB1 receptor in the amygdala.

Read more: http://goo.gl/bN3HY


Global Source and/or and/or more resources and/or read more: http://goo.gl/JujXk ─ Publisher and/or Author and/or Managing Editor:__Andres Agostini ─ @Futuretronium at Twitter! Futuretronium Book at http://goo.gl/JujXk

Monday, September 19, 2011

 2045: THE YEAR MAN BECOMES IMMORTAL

On Feb. 15, 1965, a diffident but self-possessed high school student named Raymond Kurzweil appeared as a guest on a game show called I've Got a Secret. He was introduced by the host, Steve Allen, then he played a short musical composition on a piano. The idea was that Kurzweil was hiding an unusual fact and the panelists — they included a comedian and a former Miss America — had to guess what it was.

On the show (see the clip on YouTube), the beauty queen did a good job of grilling Kurzweil, but the comedian got the win: the music was composed by a computer. Kurzweil got $200. (Watch TIME's video "Singularity: How Scared Should We Be?")

Kurzweil then demonstrated the computer, which he built himself — a desk-size affair with loudly clacking relays, hooked up to a typewriter. The panelists were pretty blasé about it; they were more impressed by Kurzweil's age than by anything he'd actually done. They were ready to move on to Mrs. Chester Loney of Rough and Ready, Calif., whose secret was that she'd been President Lyndon Johnson's first-grade teacher.

But Kurzweil would spend much of the rest of his career working out what his demonstration meant. Creating a work of art is one of those activities we reserve for humans and humans only. It's an act of self-expression; you're not supposed to be able to do it if you don't have a self. To see creativity, the exclusive domain of humans, usurped by a computer built by a 17-year-old is to watch a line blur that cannot be unblurred, the line between organic intelligence and artificial intelligence.

That was Kurzweil's real secret, and back in 1965 nobody guessed it. Maybe not even him, not yet. But now, 46 years later, Kurzweil believes that we're approaching a moment when computers will become intelligent, and not just intelligent but more intelligent than humans. When that happens, humanity — our bodies, our minds, our civilization — will be completely and irreversibly transformed. He believes that this moment is not only inevitable but imminent. According to his calculations, the end of human civilization as we know it is about 35 years away. (See the best inventions of 2010.)

Computers are getting faster. Everybody knows that. Also, computers are getting faster faster — that is, the rate at which they're getting faster is increasing.

True? True.

So if computers are getting so much faster, so incredibly fast, there might conceivably come a moment when they are capable of something comparable to human intelligence. Artificial intelligence. All that horsepower could be put in the service of emulating whatever it is our brains are doing when they create consciousness — not just doing arithmetic very quickly or composing piano music but also driving cars, writing books, making ethical decisions, appreciating fancy paintings, making witty observations at cocktail parties.

If you can swallow that idea, and Kurzweil and a lot of other very smart people can, then all bets are off. From that point on, there's no reason to think computers would stop getting more powerful. They would keep on developing until they were far more intelligent than we are. Their rate of development would also continue to increase, because they would take over their own development from their slower-thinking human creators. Imagine a computer scientist that was itself a super-intelligent computer. It would work incredibly quickly. It could draw on huge amounts of data effortlessly. It wouldn't even take breaks to play Farmville. (See the best inventions of 2010.)

Probably. It's impossible to predict the behavior of these smarter-than-human intelligences with which (with whom?) we might one day share the planet, because if you could, you'd be as smart as they would be. But there are a lot of theories about it. Maybe we'll merge with them to become super-intelligent cyborgs, using computers to extend our intellectual abilities the same way that cars and planes extend our physical abilities. Maybe the artificial intelligences will help us treat the effects of old age and prolong our life spans indefinitely. Maybe we'll scan our consciousnesses into computers and live inside them as software, forever, virtually. Maybe the computers will turn on humanity and annihilate us. The one thing all these theories have in common is the transformation of our species into something that is no longer recognizable as such to humanity circa 2011. This transformation has a name: the Singularity.

The difficult thing to keep sight of when you're talking about the Singularity is that even though it sounds like science fiction, it isn't, no more than a weather forecast is science fiction. It's not a fringe idea; it's a serious hypothesis about the future of life on Earth. There's an intellectual gag reflex that kicks in anytime you try to swallow an idea that involves super-intelligent immortal cyborgs, but suppress it if you can, because while the Singularity appears to be, on the face of it, preposterous, it's an idea that rewards sober, careful evaluation.

See pictures of cinema's most memorable robots.

From TIME's archives: "Can Machines Think?"

See TIME's special report on gadgets, then and now.

People are spending a lot of money trying to understand it. The three-year-old Singularity University, which offers inter-disciplinary courses of study for graduate students and executives, is hosted by NASA. Google was a founding sponsor; its CEO and co-founder Larry Page spoke there last year. People are attracted to the Singularity for the shock value, like an intellectual freak show, but they stay because there's more to it than they expected. And of course, in the event that it turns out to be real, it will be the most important thing to happen to human beings since the invention of language. (See "Is Technology Making Us Lonelier?")

The Singularity isn't a wholly new idea, just newish. In 1965 the British mathematician I.J. Good described something he called an "intelligence explosion":

Let an ultraintelligent machine be defined as a machine that can far surpass all the intellectual activities of any man however clever. Since the design of machines is one of these intellectual activities, an ultraintelligent machine could design even better machines; there would then unquestionably be an "intelligence explosion," and the intelligence of man would be left far behind. Thus the first ultraintelligent machine is the last invention that man need ever make.

The word singularity is borrowed from astrophysics: it refers to a point in space-time — for example, inside a black hole — at which the rules of ordinary physics do not apply. In the 1980s the science-fiction novelist Vernor Vinge attached it to Good's intelligence-explosion scenario. At a NASA symposium in 1993, Vinge announced that "within 30 years, we will have the technological means to create super-human intelligence. Shortly after, the human era will be ended."

By that time Kurzweil was thinking about the Singularity too. He'd been busy since his appearance on I've Got a Secret. He'd made several fortunes as an engineer and inventor; he founded and then sold his first software company while he was still at MIT. He went on to build the first print-to-speech reading machine for the blind — Stevie Wonder was customer No. 1 — and made innovations in a range of technical fields, including music synthesizers and speech recognition. He holds 39 patents and 19 honorary doctorates. In 1999 President Bill Clinton awarded him the National Medal of Technology. (See pictures of adorable robots.)

But Kurzweil was also pursuing a parallel career as a futurist: he has been publishing his thoughts about the future of human and machine-kind for 20 years, most recently in The Singularity Is Near, which was a best seller when it came out in 2005. A documentary by the same name, starring Kurzweil, Tony Robbins and Alan Dershowitz, among others, was released in January. (Kurzweil is actually the subject of two current documentaries. The other one, less authorized but more informative, is called The Transcendent Man.) Bill Gates has called him "the best person I know at predicting the future of artificial intelligence."(See the world's most influential people in the 2010 TIME 100.)

In real life, the transcendent man is an unimposing figure who could pass for Woody Allen's even nerdier younger brother. Kurzweil grew up in Queens, N.Y., and you can still hear a trace of it in his voice. Now 62, he speaks with the soft, almost hypnotic calm of someone who gives 60 public lectures a year. As the Singularity's most visible champion, he has heard all the questions and faced down the incredulity many, many times before. He's good-natured about it. His manner is almost apologetic: I wish I could bring you less exciting news of the future, but I've looked at the numbers, and this is what they say, so what else can I tell you?

Kurzweil's interest in humanity's cyborganic destiny began about 1980 largely as a practical matter. He needed ways to measure and track the pace of technological progress. Even great inventions can fail if they arrive before their time, and he wanted to make sure that when he released his, the timing was right. "Even at that time, technology was moving quickly enough that the world was going to be different by the time you finished a project," he says. "So it's like skeet shooting — you can't shoot at the target." He knew about Moore's law, of course, which states that the number of transistors you can put on a microchip doubles about every two years. It's a surprisingly reliable rule of thumb. Kurzweil tried plotting a slightly different curve: the change over time in the amount of computing power, measured in MIPS (millions of instructions per second), that you can buy for $1,000.

As it turned out, Kurzweil's numbers looked a lot like Moore's. They doubled every couple of years. Drawn as graphs, they both made exponential curves, with their value increasing by multiples of two instead of by regular increments in a straight line. The curves held eerily steady, even when Kurzweil extended his backward through the decades of pretransistor computing technologies like relays and vacuum tubes, all the way back to 1900. (Comment on this story.)

Kurzweil then ran the numbers on a whole bunch of other key technological indexes — the falling cost of manufacturing transistors, the rising clock speed of microprocessors, the plummeting price of dynamic RAM. He looked even further afield at trends in biotech and beyond — the falling cost of sequencing DNA and of wireless data service and the rising numbers of Internet hosts and nanotechnology patents. He kept finding the same thing: exponentially accelerating progress. "It's really amazing how smooth these trajectories are," he says. "Through thick and thin, war and peace, boom times and recessions." Kurzweil calls it the law of accelerating returns: technological progress happens exponentially, not linearly.

See TIME's video "Five Worst Inventions."

See the 100 best gadgets of all time.

Then he extended the curves into the future, and the growth they predicted was so phenomenal, it created cognitive resistance in his mind. Exponential curves start slowly, then rocket skyward toward infinity. According to Kurzweil, we're not evolved to think in terms of exponential growth. "It's not intuitive. Our built-in predictors are linear. When we're trying to avoid an animal, we pick the linear prediction of where it's going to be in 20 seconds and what to do about it. That is actually hardwired in our brains."

Here's what the exponential curves told him. We will successfully reverse-engineer the human brain by the mid-2020s. By the end of that decade, computers will be capable of human-level intelligence. Kurzweil puts the date of the Singularity — never say he's not conservative — at 2045. In that year, he estimates, given the vast increases in computing power and the vast reductions in the cost of same, the quantity of artificial intelligence created will be about a billion times the sum of all the human intelligence that exists today. (See how robotics are changing the future of medicine.)

The Singularity isn't just an idea. it attracts people, and those people feel a bond with one another. Together they form a movement, a subculture; Kurzweil calls it a community. Once you decide to take the Singularity seriously, you will find that you have become part of a small but intense and globally distributed hive of like-minded thinkers known as Singularitarians.

Not all of them are Kurzweilians, not by a long chalk. There's room inside Singularitarianism for considerable diversity of opinion about what the Singularity means and when and how it will or won't happen. But Singularitarians share a worldview. They think in terms of deep time, they believe in the power of technology to shape history, they have little interest in the conventional wisdom about anything, and they cannot believe you're walking around living your life and watching TV as if the artificial-intelligence revolution were not about to erupt and change absolutely everything. They have no fear of sounding ridiculous; your ordinary citizen's distaste for apparently absurd ideas is just an example of irrational bias, and Singularitarians have no truck with irrationality. When you enter their mind-space you pass through an extreme gradient in worldview, a hard ontological shear that separates Singularitarians from the common run of humanity. Expect turbulence.

In addition to the Singularity University, which Kurzweil co-founded, there's also a Singularity Institute for Artificial Intelligence, based in San Francisco. It counts among its advisers Peter Thiel, a former CEO of PayPal and an early investor in Facebook. The institute holds an annual conference called the Singularity Summit. (Kurzweil co-founded that too.) Because of the highly interdisciplinary nature of Singularity theory, it attracts a diverse crowd. Artificial intelligence is the main event, but the sessions also cover the galloping progress of, among other fields, genetics and nanotechnology. (See TIME's computer covers.)

At the 2010 summit, which took place in August in San Francisco, there were not just computer scientists but also psychologists, neuroscientists, nanotechnologists, molecular biologists, a specialist in wearable computers, a professor of emergency medicine, an expert on cognition in gray parrots and the professional magician and debunker James "the Amazing" Randi. The atmosphere was a curious blend of Davos and UFO convention. Proponents of seasteading — the practice, so far mostly theoretical, of establishing politically autonomous floating communities in international waters — handed out pamphlets. An android chatted with visitors in one corner.

After artificial intelligence, the most talked-about topic at the 2010 summit was life extension. Biological boundaries that most people think of as permanent and inevitable Singularitarians see as merely intractable but solvable problems. Death is one of them. Old age is an illness like any other, and what do you do with illnesses? You cure them. Like a lot of Singularitarian ideas, it sounds funny at first, but the closer you get to it, the less funny it seems. It's not just wishful thinking; there's actual science going on here.

For example, it's well known that one cause of the physical degeneration associated with aging involves telomeres, which are segments of DNA found at the ends of chromosomes. Every time a cell divides, its telomeres get shorter, and once a cell runs out of telomeres, it can't reproduce anymore and dies. But there's an enzyme called telomerase that reverses this process; it's one of the reasons cancer cells live so long. So why not treat regular non-cancerous cells with telomerase? In November, researchers at Harvard Medical School announced in Nature that they had done just that. They administered telomerase to a group of mice suffering from age-related degeneration. The damage went away. The mice didn't just get better; they got younger. (Comment on this story.)

Aubrey de Grey is one of the world's best-known life-extension researchers and a Singularity Summit veteran. A British biologist with a doctorate from Cambridge and a famously formidable beard, de Grey runs a foundation called SENS, or Strategies for Engineered Negligible Senescence. He views aging as a process of accumulating damage, which he has divided into seven categories, each of which he hopes to one day address using regenerative medicine. "People have begun to realize that the view of aging being something immutable — rather like the heat death of the universe — is simply ridiculous," he says. "It's just childish. The human body is a machine that has a bunch of functions, and it accumulates various types of damage as a side effect of the normal function of the machine. Therefore in principal that damage can be repaired periodically. This is why we have vintage cars. It's really just a matter of paying attention. The whole of medicine consists of messing about with what looks pretty inevitable until you figure out how to make it not inevitable."

Kurzweil takes life extension seriously too. His father, with whom he was very close, died of heart disease at 58. Kurzweil inherited his father's genetic predisposition; he also developed Type 2 diabetes when he was 35. Working with Terry Grossman, a doctor who specializes in longevity medicine, Kurzweil has published two books on his own approach to life extension, which involves taking up to 200 pills and supplements a day. He says his diabetes is essentially cured, and although he's 62 years old from a chronological perspective, he estimates that his biological age is about 20 years younger.

From TIME's archives: "The Immortality Enzyme."

See Healthland's 5 rules for good health in 2011.

But his goal differs slightly from de Grey's. For Kurzweil, it's not so much about staying healthy as long as possible; it's about staying alive until the Singularity. It's an attempted handoff. Once hyper-intelligent artificial intelligences arise, armed with advanced nanotechnology, they'll really be able to wrestle with the vastly complex, systemic problems associated with aging in humans. Alternatively, by then we'll be able to transfer our minds to sturdier vessels such as computers and robots. He and many other Singularitarians take seriously the proposition that many people who are alive today will wind up being functionally immortal.

It's an idea that's radical and ancient at the same time. In "Sailing to Byzantium," W.B. Yeats describes mankind's fleshly predicament as a soul fastened to a dying animal. Why not unfasten it and fasten it to an immortal robot instead? But Kurzweil finds that life extension produces even more resistance in his audiences than his exponential growth curves. "There are people who can accept computers being more intelligent than people," he says. "But the idea of significant changes to human longevity — that seems to be particularly controversial. People invested a lot of personal effort into certain philosophies dealing with the issue of life and death. I mean, that's the major reason we have religion." (See the top 10 medical breakthroughs of 2010.)

Of course, a lot of people think the Singularity is nonsense — a fantasy, wishful thinking, a Silicon Valley version of the Evangelical story of the Rapture, spun by a man who earns his living making outrageous claims and backing them up with pseudoscience. Most of the serious critics focus on the question of whether a computer can truly become intelligent.

The entire field of artificial intelligence, or AI, is devoted to this question. But AI doesn't currently produce the kind of intelligence we associate with humans or even with talking computers in movies — HAL or C3PO or Data. Actual AIs tend to be able to master only one highly specific domain, like interpreting search queries or playing chess. They operate within an extremely specific frame of reference. They don't make conversation at parties. They're intelligent, but only if you define intelligence in a vanishingly narrow way. The kind of intelligence Kurzweil is talking about, which is called strong AI or artificial general intelligence, doesn't exist yet.

Why not? Obviously we're still waiting on all that exponentially growing computing power to get here. But it's also possible that there are things going on in our brains that can't be duplicated electronically no matter how many MIPS you throw at them. The neurochemical architecture that generates the ephemeral chaos we know as human consciousness may just be too complex and analog to replicate in digital silicon. The biologist Dennis Bray was one of the few voices of dissent at last summer's Singularity Summit. "Although biological components act in ways that are comparable to those in electronic circuits," he argued, in a talk titled "What Cells Can Do That Robots Can't," "they are set apart by the huge number of different states they can adopt. Multiple biochemical processes create chemical modifications of protein molecules, further diversified by association with distinct structures at defined locations of a cell. The resulting combinatorial explosion of states endows living systems with an almost infinite capacity to store information regarding past and present conditions and a unique capacity to prepare for future events." That makes the ones and zeros that computers trade in look pretty crude. (See how to live 100 years.)

Underlying the practical challenges are a host of philosophical ones. Suppose we did create a computer that talked and acted in a way that was indistinguishable from a human being — in other words, a computer that could pass the Turing test. (Very loosely speaking, such a computer would be able to pass as human in a blind test.) Would that mean that the computer was sentient, the way a human being is? Or would it just be an extremely sophisticated but essentially mechanical automaton without the mysterious spark of consciousness — a machine with no ghost in it? And how would we know?

Even if you grant that the Singularity is plausible, you're still staring at a thicket of unanswerable questions. If I can scan my consciousness into a computer, am I still me? What are the geopolitics and the socioeconomics of the Singularity? Who decides who gets to be immortal? Who draws the line between sentient and nonsentient? And as we approach immortality, omniscience and omnipotence, will our lives still have meaning? By beating death, will we have lost our essential humanity?

Kurzweil admits that there's a fundamental level of risk associated with the Singularity that's impossible to refine away, simply because we don't know what a highly advanced artificial intelligence, finding itself a newly created inhabitant of the planet Earth, would choose to do. It might not feel like competing with us for resources. One of the goals of the Singularity Institute is to make sure not just that artificial intelligence develops but also that the AI is friendly. You don't have to be a super-intelligent cyborg to understand that introducing a superior life-form into your own biosphere is a basic Darwinian error. (Comment on this story.)

If the Singularity is coming, these questions are going to get answers whether we like it or not, and Kurzweil thinks that trying to put off the Singularity by banning technologies is not only impossible but also unethical and probably dangerous. "It would require a totalitarian system to implement such a ban," he says. "It wouldn't work. It would just drive these technologies underground, where the responsible scientists who we're counting on to create the defenses would not have easy access to the tools."

Kurzweil is an almost inhumanly patient and thorough debater. He relishes it. He's tireless in hunting down his critics so that he can respond to them, point by point, carefully and in detail.

See TIME's photo-essay "A Global Look at Longevity."

See how genes, gender and diet may be life extenders.

Take the question of whether computers can replicate the biochemical complexity of an organic brain. Kurzweil yields no ground there whatsoever. He does not see any fundamental difference between flesh and silicon that would prevent the latter from thinking. He defies biologists to come up with a neurological mechanism that could not be modeled or at least matched in power and flexibility by software running on a computer. He refuses to fall on his knees before the mystery of the human brain. "Generally speaking," he says, "the core of a disagreement I'll have with a critic is, they'll say, Oh, Kurzweil is underestimating the complexity of reverse-engineering of the human brain or the complexity of biology. But I don't believe I'm underestimating the challenge. I think they're underestimating the power of exponential growth."

This position doesn't make Kurzweil an outlier, at least among Singularitarians. Plenty of people make more-extreme predictions. Since 2005 the neuroscientist Henry Markram has been running an ambitious initiative at the Brain Mind Institute of the Ecole Polytechnique in Lausanne, Switzerland. It's called the Blue Brain project, and it's an attempt to create a neuron-by-neuron simulation of a mammalian brain, using IBM's Blue Gene super-computer. So far, Markram's team has managed to simulate one neocortical column from a rat's brain, which contains about 10,000 neurons. Markram has said that he hopes to have a complete virtual human brain up and running in 10 years. (Even Kurzweil sniffs at this. If it worked, he points out, you'd then have to educate the brain, and who knows how long that would take?) (See portraits of centenarians.)

By definition, the future beyond the Singularity is not knowable by our linear, chemical, animal brains, but Kurzweil is teeming with theories about it. He positively flogs himself to think bigger and bigger; you can see him kicking against the confines of his aging organic hardware. "When people look at the implications of ongoing exponential growth, it gets harder and harder to accept," he says. "So you get people who really accept, yes, things are progressing exponentially, but they fall off the horse at some point because the implications are too fantastic. I've tried to push myself to really look."

In Kurzweil's future, biotechnology and nanotechnology give us the power to manipulate our bodies and the world around us at will, at the molecular level. Progress hyperaccelerates, and every hour brings a century's worth of scientific breakthroughs. We ditch Darwin and take charge of our own evolution. The human genome becomes just so much code to be bug-tested and optimized and, if necessary, rewritten. Indefinite life extension becomes a reality; people die only if they choose to. Death loses its sting once and for all. Kurzweil hopes to bring his dead father back to life.

We can scan our consciousnesses into computers and enter a virtual existence or swap our bodies for immortal robots and light out for the edges of space as intergalactic godlings. Within a matter of centuries, human intelligence will have re-engineered and saturated all the matter in the universe. This is, Kurzweil believes, our destiny as a species. (See the costs of living a long life.)

Or it isn't. When the big questions get answered, a lot of the action will happen where no one can see it, deep inside the black silicon brains of the computers, which will either bloom bit by bit into conscious minds or just continue in ever more brilliant and powerful iterations of nonsentience.

But as for the minor questions, they're already being decided all around us and in plain sight. The more you read about the Singularity, the more you start to see it peeking out at you, coyly, from unexpected directions. Five years ago we didn't have 600 million humans carrying out their social lives over a single electronic network. Now we have Facebook. Five years ago you didn't see people double-checking what they were saying and where they were going, even as they were saying it and going there, using handheld network-enabled digital prosthetics. Now we have iPhones. Is it an unimaginable step to take the iPhones out of our hands and put them into our skulls?

Already 30,000 patients with Parkinson's disease have neural implants. Google is experimenting with computers that can drive cars. There are more than 2,000 robots fighting in Afghanistan alongside the human troops. This month a game show will once again figure in the history of artificial intelligence, but this time the computer will be the guest: an IBM super-computer nicknamed Watson will compete on Jeopardy! Watson runs on 90 servers and takes up an entire room, and in a practice match in January it finished ahead of two former champions, Ken Jennings and Brad Rutter. It got every question it answered right, but much more important, it didn't need help understanding the questions (or, strictly speaking, the answers), which were phrased in plain English. Watson isn't strong AI, but if strong AI happens, it will arrive gradually, bit by bit, and this will have been one of the bits. (Comment on this story.)

A hundred years from now, Kurzweil and de Grey and the others could be the 22nd century's answer to the Founding Fathers — except unlike the Founding Fathers, they'll still be alive to get credit — or their ideas could look as hilariously retro and dated as Disney's Tomorrowland. Nothing gets old as fast as the future.

But even if they're dead wrong about the future, they're right about the present. They're taking the long view and looking at the big picture. You may reject every specific article of the Singularitarian charter, but you should admire Kurzweil for taking the future seriously. Singularitarianism is grounded in the idea that change is real and that humanity is in charge of its own fate and that history might not be as simple as one damn thing after another. Kurzweil likes to point out that your average cell phone is about a millionth the size of, a millionth the price of and a thousand times more powerful than the computer he had at MIT 40 years ago. Flip that forward 40 years and what does the world look like? If you really want to figure that out, you have to think very, very far outside the box. Or maybe you have to think further inside it than anyone ever has before.

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Sunday, September 18, 2011

How to print a clock, or a house … or another printer

MIT is pushing the boundaries of the 3D printing technology (“3DP“) it helped pioneer nearly two decades ago.

3DP printers build 3D solid objects by spreading layers of supported materials over movable control surfaces. Current models can use a variety of materials, including metals, and can include colors in printed objects.

One former Media Lab student, Peter Schmitt PhD ’11, working with Media Lab IP consultant Bob Swartz, has printed entire working clocks — with all their gears, chains, faces and hands in a single unit — ready to start ticking as soon as the surplus powder is washed away.

But take it a step further: imagine being able to “print” an entire house or building. A system for doing just that by “printing” concrete is being developed by the MIT Media Lab’s Neri Oxman and her graduate student Steven Keating. The technique could make it possible to create fanciful, organic-looking shapes that would be difficult or impossible using molds. It could also allow the properties of the concrete itself to vary continuously, producing structures that are both lighter and stronger than conventional concrete.

This variable-density printing is not just about large-scale objects. Oxman has designed a chair made of different polymers, for example, producing stiff areas for structural support and flexible areas for comfort, all printed out as a single unit.

Peter Schmitt, now a visiting scientist at the Media Lab, is pushing the technology in an even more sci-fi direction, trying to “build machines that could build machines,” he says. So far, he’s succeeded in making machines that can make many of the parts for another machine, but there remain many obstacles in establishing connections among these — and it’s still more of an intellectual exercise than a practical system, he concedes.

“There are better ways to make the parts,” he says. “But at some point, these kinds of things will happen.”

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Scientists create first step toward creating ‘inorganic life’

University of Glasgow scientists have taken their first tentative steps towards creating “life” from inorganic chemical cells (iCHELLS), potentially defining the new area of “inorganic biology.”

“What we are trying do is create self-replicating, evolving inorganic cells that would essentially be alive. You could call it inorganic biology,” said Professor Lee Cronin, University of Glagow Gardiner Chair of Chemistry in the College of Science and Engineering.

The cells can be compartmentalized by creating internal membranes that control the passage of materials and energy through them, meaning several chemical processes can be isolated within the same cell — just like biological cells.

The researchers say the cells, which can also store electricity, could potentially be used in all sorts of applications in medicine, as sensors or to confine chemical reactions.

The research is part of a project by Prof Cronin to demonstrate that inorganic chemical compounds are capable of self-replicating and evolving, just as organic, biological carbon-based cells do. “The grand aim is to construct complex chemical cells with life-like properties that could help us understand how life emerged and also to use this approach to define a new technology based upon evolution in the material world — a kind of inorganic living technology.

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Smartphone battery life could dramatically improve with new invention

University of Michigan computer scientists have developed a new “subconscious mode” for smartphones and other WiFi-enabled mobile devices that could extend battery life by as much as 54 percent for users on the busiest networks. It’s called E-MiLi (Energy-Minimizing Idle Listening).

Even when smartphones are in power-saving modes and not actively sending or receiving messages, they are still on alert for incoming information and they’re searching for a clear communication channel. Devices in power-saving modes spend 60 to 80 percent of their time in idle listening, expending roughly the same amount of power as they do when they’re fully awake, the researchers found.

E-MiLi slows down the WiFi card’s clock speed to 1/16 of its normal frequency, but jolts it back to full speed when the phone detects message headers coming in. When used with power-saving mode, the researchers found that E-MiLi is capable of reducing energy consumption by around 44 percent for 92 percent of mobile devices in real-world wireless networks.

Implementing it would not be simple, though. E-MiLi requires new firmware for phones and computers that would be sending messages, WiFi chipset manufacturers would have to adopt these firmware modifications, and then companies that make smartphones and computers would have to incorporate the new chips into their products.

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Carbon nanoparticles break barriers — and that may not be good

Researchers from the schools of science and medicine at Indiana University-Purdue University Indianapolis (IUPUI) have examined the effects of carbon nanoparticles (CNPs) on living cells. This work is among the first to study CNPs at concentrations low enough to mimic the actual exposure of an ordinary individual.

The effects on the human body of exposure to CNPs are just beginning to be revealed. Exposure at the level studied by the IUPUI researchers is approximately equivalent to what might be the result of improperly disposing of an item such as a television or computer monitor containing CNPs, living near a CNP-producing facility, or working with CNPs.

The research focuses on the effect of low concentration CNP exposure on kidney cells. The investigators found significant and potentially worrisome effects.

“Unlike many other studies, we have used low concentrations of CNPs that are typical of what might appear in the body after ingesting them from environmental contamination or even from breathing air with CNPs. We found that these minute particles cause leakage in the cellular lining of the renal nephron,” said study first author Bonnie Blazer-Yost, Ph.D. “Breaching this biological barrier concerns us because things that should be retained in the forming urine can leak back into the blood stream and things in the blood can leak into the urine. Normal biological substances as well as waste products are dangerous if they go where they are not supposed to be.”

“These CNPs don’t kill cells — so they are not lethal, but they do affect cells, and in this case it’s an adverse effect,” said corresponding and senior author Frank Witzmann, Ph.D. Biological barriers are very important to human health. The most well understood is the skin, but there are many others. “The human body needs intact barriers, whether it be skin, airway linings, gut walls or the kidney cells we looked at in this study. We need to gain a better understanding of how CNPs modify and change characteristics of barriers as these tiny particles become more common in the air we breathe,” he said.

The two researchers note that these incredibly strong particles, visible only under an electron microscope, are useful for drug delivery and advanced electronics.  What they worry about is the danger to human exposure to CNPs from inappropriate manufacturing and disposal procedures.

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How to Make Your Hard Drive Infinite

Hard drives are constantly getting bigger, but it seems we fill them up with data just as quickly anyway. The solution may be a small piece of software from a startup called Bitcasa; when you install it, the capacity of your computer's hard drive becomes, essentially, infinite.

"Look at the bottom of my finder [file browser] window," says Tony Gauda, one of the cofounders of the company, a finalist in a competition for new startups at the Disrupt conference in San Francisco this week. "It says 18 terabytes available, because Apple's operating system doesn't understand numbers any bigger, but I can actually save infinite data if I want to."

Bitcasa is currently in a limited beta; users pay $10 a month for unlimited storage. The software only works on Apple computers, but a Windows version is in development, and mobile apps for smart phones and tablets are planned, too. "We want you to be able to have one infinitely large store of your files and data that you can access from any device," says Gauda. "We will be the last storage device or service you ever buy."

Bitcasa creates the illusion that data stored on distant cloud servers is actually kept on the physical hard drive inside a machine. When that computer's user opens a file browser window, all files and folders appear to be stored locally.

As a file stored in Bitcasa's cloud is opened, it is downloaded to the computer as quickly as possible. "The network is good enough that it can be your hard drive now," says Gauda. "It performs well enough that you won't notice that we're streaming a movie to you rather than playing it off your hard drive."

Bitcasa's software shuffles a user's data around to ensure that the most-used files are stored locally, on a computer's built-in hard drive, to minimize the effects of slow or missing connections. "We analyze how you use your data by looking at things like how old a file is, or when you last used it, to decide what gets put into the cloud, but you can also specify folders that should always be stored locally," Gauda explains. Holiday snaps from a couple of years ago, for example, would reside on Bitcasa's servers. A document created last week is more likely to be stored on the computer's hard drive.

No matter how well Bitcasa guesses what you need, some files must be fetched from the cloud before they can be accessed. Because not everyone has a perfect connection, some users might not get a seamless experience. And if a computer is offline, some files will simply be unavailable.

Inviting people to store "infinite" data requires Bitcasa to provide a lot of storage space. The company plans to keep the expense of all that storage to a minimum by tracking if a file it needs to store for one user is an exact copy of something already being stored in the cloud for someone else—a popular music track, for example. In such situations, Bitcasa needs to store only one copy, Gauda says.

The notion of cloud storage seamlessly extending a computer's hard drive has already gained considerable popularity in the form of Dropbox. A Dropbox folder on a user's computer is always mirrored in the cloud, as well as on a user's other computers. The company provides two gigabytes of storage for free, and 50 gigabytes of storage for $10 a month. Bitcasa says it will offer unlimited amounts for the same price, but the new company might need to introduce premium options, perhaps for businesses, if users chew up large amounts of capacity. Cloud backup service Mozy had to withdraw its "unlimited" storage option earlier this year because it cost too much to maintain.

After seeing Bitcasa's demonstration at the Disrupt event, venture capitalist Roelhof Botha of Sequoia Capital, which has invested in Dropbox, noted that storing and transporting so much data would be a challenge. "It's going to be expensive to stream all that data," he said.

Angel investor Ron Conway said he expected the startup to face stiff competition from Dropbox, now valued at over $1 billion. Conway was one of Dropbox's early stage investors. Conway added, however, that Bitcasa has already shown off technology that could set it apart. "The thing that caught my eye was the streaming video," he said. "That seems really difficult for other services to do."

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 Smart watches to provide faster access to smartphone information

Meta Watch Ltd. has announced it has acquired the Meta Watch branded connected watch business from Fossil, Inc. It plans to release wrist-based devices later this month for about $200 in the U.S. and Europe.

The announcement is evidence of the mounting interest in connected or smart watches. Early adopters of smart watches comment on how surprisingly useful they can be. A smart watch can connect wirelessly to your smartphone and display e-mails and SMS messages, for example, eliminating the need to constantly pull a phone from a pocket or purse.

Other smart-watch uses include alerts, notifications, social networking service updates, turn-by-turn directions, sports performance feedback, and music control, Meta Watch says.

“Over the next 10 years, billions of people will carry smart phones, changing how consumers live and creating new opportunities and markets for connected watches and other wearable devices,” said Juha Pinomaa, Chairman of Meta Watch.

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Thursday, September 15, 2011

 An Immune System Trained to Kill Cancer

PHILADELPHIA — A year ago, when chemotherapy stopped working against his leukemia, William Ludwig signed up to be the first patient treated in a bold experiment at the University of Pennsylvania. Mr. Ludwig, then 65, a retired corrections officer from Bridgeton, N.J., felt his life draining away and thought he had nothing to lose.

Doctors removed a billion of his T-cells — a type of white blood cell that fights viruses and tumors — and gave them new genes that would program the cells to attack his cancer. Then the altered cells were dripped back into Mr. Ludwig’s veins.

At first, nothing happened. But after 10 days, hell broke loose in his hospital room. He began shaking with chills. His temperature shot up. His blood pressure shot down. He became so ill that doctors moved him into intensive care and warned that he might die. His family gathered at the hospital, fearing the worst.

A few weeks later, the fevers were gone. And so was the leukemia.

There was no trace of it anywhere — no leukemic cells in his blood or bone marrow, no more bulging lymph nodes on his CT scan. His doctors calculated that the treatment had killed off two pounds of cancer cells.

A year later, Mr. Ludwig is still in complete remission. Before, there were days when he could barely get out of bed; now, he plays golf and does yard work.

“I have my life back,” he said.

Mr. Ludwig’s doctors have not claimed that he is cured — it is too soon to tell — nor have they declared victory over leukemia on the basis of this experiment, which involved only three patients. The research, they say, has far to go; the treatment is still experimental, not available outside of studies.

But scientists say the treatment that helped Mr. Ludwig, described recently in The New England Journal of Medicine and Science Translational Medicine, may signify a turning point in the long struggle to develop effective gene therapies against cancer. And not just for leukemia patients: other cancers may also be vulnerable to this novel approach — which employs a disabled form of H.I.V.-1, the virus that causes AIDS, to carry cancer-fighting genes into the patients’ T-cells. In essence, the team is using gene therapy to accomplish something that researchers have hoped to do for decades: train a person’s own immune system to kill cancer cells.

Two other patients have undergone the experimental treatment. One had a partial remission: his disease lessened but did not go away completely. Another had a complete remission. All three had had advanced chronic lymphocytic leukemia and had run out of chemotherapy options. Usually, the only hope for a remission in such cases is a bone-marrow transplant, but these patients were not candidates for it.

Dr. Carl June, who led the research and directs translational medicine in the Abramson Cancer Center at the University of Pennsylvania, said that the results stunned even him and his colleagues, Dr. David L. Porter, Bruce Levine and Michael Kalos. They had hoped to see some benefit but had not dared dream of complete, prolonged remissions. Indeed, when Mr. Ludwig began running fevers, the doctors did not realize at first that it was a sign that his T-cells were engaged in a furious battle with his cancer.

Other experts in the field said the results were a major advance.

“It’s great work,” said Dr. Walter J. Urba of the Providence Cancer Center and Earle A. Chiles Research Institute in Portland, Ore. He called the patients’ recoveries remarkable, exciting and significant. “I feel very positive about this new technology. Conceptually, it’s very, very big.”

Dr. Urba said he thought the approach would ultimately be used against other types of cancer as well as leukemia and lymphoma. But he cautioned, “For patients today, we’re not there yet.” And he added the usual scientific caveat: To be considered valid, the results must be repeated in more patients, and by other research teams.

Dr. June called the techniques “a harvest of the information from the molecular biology revolution over the past two decades.”

Hitting a Genetic Jackpot

To make T-cells search out and destroy cancer, researchers must equip them to do several tasks: recognize the cancer, attack it, multiply, and live on inside the patient. A number of research groups have been trying to do this, but the T-cells they engineered could not accomplish all the tasks. As a result, the cells’ ability to fight tumors has generally been temporary.

The University of Pennsylvania team seems to have hit all the targets at once. Inside the patients, the T-cells modified by the researchers multiplied to 1,000 to 10,000 times the number infused, wiped out the cancer and then gradually diminished, leaving a population of “memory” cells that can quickly proliferate again if needed.

The researchers said they were not sure which parts of their strategy made it work — special cell-culturing techniques, the use of H.I.V.-1 to carry new genes into the T-cells, or the particular pieces of DNA that they selected to reprogram the T-cells.

The concept of doctoring T-cells genetically was first developed in the 1980s by Dr. Zelig Eshhar at the Weizmann Institute of Science in Rehovot, Israel. It involves adding gene sequences from different sources to enable the T-cells to produce what researchers call chimeric antigen receptors, or CARs — protein complexes that transform the cells into, in Dr. June’s words, “serial killers.”

Mr. Ludwig’s disease, chronic lymphocytic leukemia is a cancer of B-cells, the part of the immune system that normally produces antibodies to fight infection. All B-cells, whether healthy or leukemic, have on their surfaces a protein called CD19. To treat patients with the disease, the researchers hoped to reprogram their T-cells to find CD19 and attack B-cells carrying it.

But which gene sequences should be used to reprogram the T-cells, from which sources? And how do you insert them?

Various research groups have used different methods. Viruses are often used as carriers (or vectors) to insert DNA into other cells because that kind of genetic sabotage is exactly what viruses normally specialize in doing. To modify their patients’ T-cells, Dr. June and his colleagues tried a daring approach: they used a disabled form of H.I.V.-1. They are the first ever to use H.I.V.-1 as the vector in gene therapy for cancer patients (the virus has been used in other diseases).

The AIDS virus is a natural for this kind of treatment, Dr. June said, because it evolved to invade T-cells. The idea of putting any form of the AIDS virus into people sounds a bit frightening, he acknowledged, but the virus used by his team was “gutted” and was no longer harmful. Other researchers had altered and disabled the virus by adding DNA from humans, mice and cows, and from a virus that infects woodchucks and another that infects cows. Each bit was chosen for a particular trait, all pieced together into a vector that Dr. June called a “Rube Goldberg-like solution” and “truly a zoo.”

“It incorporates the ability of H.I.V. to infect cells but not to reproduce itself,” he said.

To administer the treatment, the researchers collected as many of the patients’ T-cells as they could by passing their blood through a machine that removed the cells and returned the other blood components back into the patients’ veins. The T-cells were exposed to the vector, which transformed them genetically, and then were frozen. Meanwhile, the patients were given chemotherapy to deplete any remaining T-cells, because the native T-cells might impede the growth of the altered ones. Finally, the T-cells were infused back into the patients.

Then, Dr. June said, “The patient becomes a bioreactor” as the T-cells proliferate, pouring out chemicals called cytokines that cause fever, chills, fatigue and other flulike symptoms.

The treatment wiped out all of the patients’ B-cells, both healthy ones and leukemic ones, and will continue to do for as long as the new T-cells persist in the body, which could be forever (and ideally should be, to keep the leukemia at bay). The lack of B-cells means that the patients may be left vulnerable to infection, and they will need periodic infusions of a substance called intravenous immune globulin to protect them.

So far, the lack of B-cells has not caused problems for Mr. Ludwig. He receives the infusions every few months. He had been receiving them even before the experimental treatment because the leukemia had already knocked out his healthy B-cells.

One thing that is not clear is why Patient 1 and Patient 3 had complete remissions, and Patient 2 did not. The researchers said that when Patient 2 developed chills and fever, he was treated with steroids at another hospital, and the drugs may have halted the T-cells’ activity. But they cannot be sure. It may also be that his disease was too severe.

The researchers wrote an entire scientific article about Patient 3, which was published in The New England Journal of Medicine. Like the other patients, he also ran fevers and felt ill, but the reaction took longer to set in, and he also developed kidney and liver trouble — a sign of tumor lysis syndrome, a condition that occurs when large numbers of cancer cells die off and dump their contents, which can clog the kidneys. He was given drugs to prevent kidney damage. He had a complete remission.

What the journal article did not mention was that Patient 3 was almost not treated.

Because of his illness and some production problems, the researchers said, they could not produce anywhere near as many altered T-cells for him as they had for the other two patients — only 14 million (“a mouse dose,” Dr. Porter said), versus 1 billion for Mr. Ludwig and 580 million for Patient 2. After debate, they decided to treat him anyway.

Patient 3 declined to be interviewed, but he wrote anonymously about his experience for the University of Pennsylvania Web site. When he developed chills and a fever, he said, “I was sure the war was on — I was sure C.L.L. cells were dying.”

He wrote that he was a scientist, and that when he was young had dreamed of someday making a discovery that would benefit mankind. But, he concluded, “I never imagined I would be part of the experiment.”

When he told Patient 3 that he was remission, Dr. Porter said, they both had tears in their eyes.

Not Without Danger to Patients

While promising, the new techniques developed by the University of Pennsylvania researchers are not without danger to patients. Engineered T-cells have attacked healthy tissue in patients at other centers. Such a reaction killed a 39-year-old woman with advanced colon cancer in a study at the National Cancer Institute, researchers there reported last year in the journal Molecular Therapy.

She developed severe breathing trouble 15 minutes after receiving the T-cells, had to be put on a ventilator and died a few days later. Apparently, a protein target on the cancer cells was also present in her lungs, and the T-cells homed in on it.

Researchers at Memorial Sloan Kettering Cancer in New York also reported a death last year in a T-cell trial for leukemia (also published in Molecular Therapy). An autopsy found that the patient had apparently died from sepsis, not from the T-cells, but because he died just four days after the infusion, the researchers said they considered the treatment a possible factor.

Dr. June said his team hopes to use T-cells against solid tumors, including some that are very hard to treat, like mesothelioma and ovarian and pancreatic cancer. But possible adverse reactions are a real concern, he said, noting that one of the protein targets on the tumor cells is also found on membranes that line the chest and abdomen. T-cell attacks could cause serious inflammation in those membranes and mimic lupus, a serious autoimmune disease.

Even if the T-cells do not hit innocent targets, there are still risks. Proteins they release could cause a “cytokine storm”— high fevers, swelling, inflammation and dangerously low blood pressure — which can be fatal. Or, if the treatment rapidly kills billions of cancer cells, the debris can damage the kidney and cause other problems.

Even if the new T-cell treatment proves to work, the drug industry will be needed to mass produce it. But Dr. June said the research is being done only at universities, not at drug companies. For the drug industry to take interest, he said, there will have to be overwhelming proof that the treatment is far better than existing ones.

“Then I think they’ll jump into it,” he said. “My challenge now is to do this in a larger set of patients with randomization, and to show that we have the same effects.”

Mr. Ludwig said that when entered the trial, he had no options left. Indeed, Dr. June said that Mr. Ludwig was “almost dead” from the leukemia, and the effort to treat him was a “Hail Mary.”

Mr. Ludwig said: “I don’t recall anybody saying there was going to be a remission. I don’t think they were dreaming to that extent.”

The trial was a Phase 1 study, meaning that its main goal was to find out whether the treatment was safe, and at what dose. Of course, doctors and patients always hope that there will be some benefit, but that was not an official endpoint.

Mr. Ludwig thought that if the trial could buy him six months or a year, it would be worth the gamble. But even if the study did not help him, he felt it would still be worthwhile if he could help the study.

When the fevers hit, he had no idea that might be a good sign. Instead, he assumed the treatment was not working. But a few weeks later, he said that his oncologist, Dr. Alison Loren, told him, “We can’t find any cancer in your bone marrow.”

Remembering the moment, Mr. Ludwig paused and said, “I got goose bumps just telling you those words.”

“I feel wonderful,” Mr. Ludwig said during a recent interview. “I walked 18 holes on the golf course this morning.”

Before the study, he was weak, suffered repeated bouts of pneumonia and was wasting away. Now, he is full of energy. He has gained 40 pounds. He and his wife bought an R.V., in which they travel with their grandson and nephew. “I feel normal, like I did 10 years before I was diagnosed,” Mr. Ludwig said. “This clinical trial saved my life.”

Dr. Loren said in an interview, “I hate to say it in that dramatic way, but I do think it saved his life.”

Mr. Ludwig said that Dr. Loren told him and his wife something he considered profound. “She said, ‘We don’t know how long it’s going to last. Enjoy every day,’ ” Mr. Ludwig recalled.

“That’s what we’ve done ever since.”

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Global Source and/or and/or more resources and/or read more: http://goo.gl/JujXk ─ Publisher and/or Author and/or Managing Editor:__Andres Agostini ─ @Futuretronium at Twitter! Futuretronium Book at http://goo.gl/JujXk