Great find, Barry. What an amazing man, and a great field to put your money
into.
--- In FairfieldLife@yahoogroups.com, turquoiseb <no_reply@...> wrote:
>
> The 20th richest man in America had a house in Santa Fe and lived a very
> quiet and inaccessible life there. But he always showed up at
> interesting charity events, and always left a big check if the people
> involved had a real vision and he felt he could help them achieve it.
> Given Mitt Romney's recent demonstration of what he thinks it is to be
> rich in America, I thought we could do with a little balance.
> Inside Paul Allen's Quest To Reverse Engineer The BrainBehind a black
> curtain in a small room a titanium sapphire laser is prepared to fire
> at a tiny and very surprising target: a half-centimeter glass window
> surgically implanted into the skull of a live mouse. If all goes right
> the laser will fire for a quadrillionth of a second while the mouse
> runs on a white, treadmill-like ball and watches a computer screen.
> Thanks to special dyes, certain brain cells will glow green if the
> mouse is using them, their image captured by cameras capable of
> detecting a single photon.
> The point to all this Star Trek style technology could not be more
> profound. That tiny tangle of tissue in the mouse's skull turns
> nerve impulses from the rodent's eyes into an interaction. Decoding
> that process would give scientists the first true window into how a
> mammalian brain experiences the world.
>
>
> It has a secondary benefit, too. Looking over the contraption puts a
> bigand pretty raresmile on the face of Paul Allen
> <http://www.forbes.com/profile/paul-allen/> , the 59-year-old Microsoft
> <http://blogs.forbes.com/microsoft/> cofounder who has plowed $500
> million into the Allen Institute for Brain Science, a medical Manhattan
> <http://www.forbes.com/places/ks/manhattan/> Project that he hopes
> will dwarf his contribution as one of the founding fathers of software.
> The institute, scattered through three buildings in Seattle
> <http://www.forbes.com/places/wa/seattle/> `s hip Fremont
> neighborhood, is primarily focused on creating tools, such as the mouse
> laser, which is technically a new type of microscope, that will allow
> scientists to understand how the soft, fleshy matter inside the human
> skull can give rise to the wondrous, mysterious creative power of the
> human mind.
>
> "As an ex-programmer I'm still just curious about how the brain
> functions, how that flow of information really happens," says Allen
> in a rare interview, in a conference room overlooking an active ship
> canal. "The thing you realize when you get into studying
> neuroscience, even a little bit, is that everything is connected to
> everything else. So it's as if the brain is trying to use
> everything at its disposalwhat it is seeing, what it is hearing,
> what is the temperature, past experience. It's using all of this to
> try to compute what the animal should do next, whether that animal is a
> mouse or human being."
>
> It's heavy stuff, fueled by curiosity and scientific ambition made
> yet weightier by issues of mortality and the neuro-fragility Allen's
> own brain has been coping with. In June his mother, Faye Allen, a
> schoolteacher who inculcated him with a love of books and knowledge,
> died of Alzheimer's. "Any time you've seen a loved
> one
," Allen says, trailing off. "You see their
> personality, everything that makes them human, slowly slipping away,
> and there is nothing you can do about it." And Allen himself has
> waged a fight against stage four non-Hodgkin's lymphoma, a deadly
> blood cancer that is now in remission. He is flush and energetic,
> juggling our interview with phone calls about one of his sports teams,
> and filled with urgency about his legacy.
>
> His first $100 million investment in the Allen Institute resulted in a
> gigantic computer map of how genes work in the brains of mice, a tool
> that other scientists have used to pinpoint genes that may play a role
> in multiple sclerosis, memory and eating disorders in people. Another
> $100 million went to creating a similar map of the human brain, already
> resulting in new theories about how the brain works, as well as maps of
> the developing mouse brain and mouse spinal cord. These have become
> essential tools for neuroscientists everywhere.
>
> Now Allen, the 20th-richest man in America, with an estimated net worth
> of $15 billion, has committed another $300 million for projects that
> will make his institute more than just a maker of tools for other
> scientists, hiring several of the top minds in neuroscience to spearhead
> them. One effort will try to understand the mouse visual cortex as a
> way to understand how nerve cells work in brains in general. Other
> projects aim to isolate all the kinds of cells in the brain and use stem
> cells to learn how they develop. Scientists think there may be 1,000 of
> these basic building blocks, but they don't even know that. "In
> software," Allen says, "we call it reverse engineering."
>
> The willingness to fund these projects has gained Allen a growing
> number of disciples. "Paul has become a hero to me," says David
> Anderson, a professor at Caltech who first proposed the mouse map
> project to Allen. "He's done something for science in a way that
> very few other philanthropists have. It required that he have faith in
> science and go where his curiosity guides him."
>
> But there are also doubts about whether his new, grander plans will
> amount to anything. "The first phase of their investment really
> worked out," says Susumu Tonegawa, an MIT professor and winner of a
> 1987 Nobel Prize who has done extensive brain research. But can
> Allen's industrial approach really solve the mystery of how the
> brain creates consciousness? "It's one of the biggest
> unresolved issues in brain research," he says. "Whether it will
> work or not, I don't know."
>
> Health issues have defined Allen's career for the past three
> decades. He left Microsoft after beating Hodgkin's lymphoma in 1982
> and never returned. Bill Gates
> <http://www.forbes.com/profile/bill-gates/> would turn Microsoft into
> one of the most essential companies of the 20th century, while Allen,
> whose shares continued to soar, spent billions on various passions.
> There were sports teams (the Portland Trail Blazers and the Seattle
> Seahawks), cable companies (Charter Communications, on which he lost $8
> billion) and research labs (the for-profit Interval Research, shut down
> in 2000). There was the first privately funded human spaceflight and
> the search for extraterrestrial life. There was the Gehry-designed EMP
> Museum, which the electric guitar buff originally built in part as a
> tribute to fellow Seattle native Jimi Hendrix. There was one of the
> largest yachts in the world, the Tatoosh, a 300-foot beauty with a
> 6-foot shaded swimming pool and a saloon that features a French
> limestone fireplace.
>
> llen began thinking about a big neuro-science project in the late
> 1990s, while he was making a flurry of investments in Seattle
> biotechnology companies. One, an outfit called Rosetta Inpharmatics,
> was doing genetic work that could be seen as a precursor of the
> Institute's Mouse Brain Atlas. Cancer researcher Stephen Friend,
> its chief executive, remembers long discussions about "a library of
> Alexandria for brain data." He set up a meeting for Allen with James
> Watson, who won the Nobel Prize for codiscovering the structure of DNA.
>
> Watson pushed Allen to think even bigger. Start an institute like
> Rockefeller University in New York or the Salk Institute in San Diego,
> he told him, and bring the best minds of science there. Allen balked,
> both at the potential $1 billion price tag and the memories of closing
> Interval Research, which failed partly because he had filled it with too
> many scientists merely completing their own projects.
>
> But the sequencing of the human genome, an example of the power of
> industrial-scale science, inspired him, and he wanted to fund something
> similar. "I'm a person that did have the ability to do something
> that would jump-start progress for scientists around the world," he
> says.
>
> But what? Allen decided to host a series of what he calls
> "charettes," or brainstorming sessions, first in Seattle, and
> then on two separate cruises with scientists on the giant Tatoosh .
> Guests included Watson; neuroscientist Richard Axel, another Nobel
> Laureate; and Leland Hartwell, a third. All the scientists proposed
> ideas close to their own interests. The psychologist and linguist
> Steven Pinker argued for a "molecule to society" institute that
> would study both neurology and behavior. Others wanted to focus on
> experimental animals, like the C. elegans worm or primates.
>
> But Caltech's Anderson, a neuroscientist and geneticist, proposed
> the winning idea: a map of how genes work in the mouse brain. Every
> cell in a mouseor, for that matter, a humanhas the same
> 20,000 genes. What makes a heart cell different from a brain cell is
> how those genes are used. And scientists can watch the genetic code
> being accessed like watching a computer reading a hard disk. In order
> to use a piece of genetic code, cells must transcribe it from DNA,
> which is stuck in the middle of the cell, to a messenger chemical
> called RNA. Scientists were learning how to measure RNA levels;
> figuring out what parts of the mouse brain use which genes would help
> neuroscientists figure out what the genes do.
>
> All of the scientists, Allen says, agreed that the project was
> worthwhiledespite every researcher having his own agenda. "It
> appealed to me because it was something that hadn't been done,
> something that could be scaled, something that created a database that
> could be accessible worldwide and would lift all boats in the area of
> neuroscience," he says. It also was similar to the role he'd
> played at Microsoft, where he had created emulators that allowed others
> to write software; again, he was creating developer tools, this time
> for neuroscientists.
>
> His mother, who loved books so much that when she was asked to name 100
> favorites she could only narrow the list to 165, was suddenly veering
> from being able to do crossword puzzles one moment to being unable to
> remember what she had just said. In early 2003 she was diagnosed with
> Alzheimer's. Allen wrote in his journal that he was "sick at
> heart," and the Allen Institute for Brain Science was started in
> short order with the first $100 million donation.
>
> Some philanthropists put their money toward buildings or
> infrastructure. Others channel it straight to the needy. Allen, in
> tackling the brain, spends it on talent. At the outset he recruited
> Allan Jones, who had worked at the genetics startup, Rosetta, that Allen
> had dabbled with, to develop the Mouse Brain Atlas. Quickly he took
> over the whole institute.
>
> Instead of hiring big-name professors, Jones recruited a platoon of 60
> young scientists taking breaks from graduate school or pit stops
> between academia and industry. Mouse brains were frozen and sliced by
> automated machines; each slice fit on a single microscope slide.
> Technicians dipped each slice in an RNA solution that stained cells
> containing a single sequence of RNA in a particular color. Only one gene
> can be captured per slice and six per brain, meaning it took 4,000 mice
> to create the Allen Brain Atlas, made available free on the Web in
> December 2004 and largely finished in 2006. The completed atlas involved
> 85 million images on 250,000 slides, or 600 terabytes of datahalf
> as big as the entire Internet in 2003.
>
> The Mouse Brain Atlas fast became a standard tool for neuroscientists
> in both industry and academia worldwide. In 2006 scientists outside
> Allen's institute had used the atlas to find genes that might
> influence susceptibility to multiple sclerosis in humans, eating
> disorders and memory. Husseini K. Manji, head of neuroscience research
> and development at Johnson & Johnson, says that his scientists scope
> out projects using the atlas' exclusive gene data. For Ed Boyden, a
> neuroscientist at MIT, looking for genes allows him to figure out what
> experiments to conduct. One of the strains of lab mice developed by the
> project has even become one of the most popular in the U.S.
>
> Outside the lab this was a dark period for Allen. In 2008 a heart
> arrhythmia required valve replacement surgery. A month later his lung
> filled with fluid, requiring another operation. When fluid built up in
> his other lung doctors diagnosed late-stage non-Hodgkin's lymphoma,
> which had spread beyond his lymph nodes. He dictated parts of his
> memoir, Idea Man , while suffering through the bone-deadening fatigue
> from chemotherapy. At the same time, Charter Communications, the cable
> company he backed, was going into bankruptcy.
>
> His exploding neuroscience hub was a welcome reprieve. Allen loved
> peppering his scientists with questions and plotting a path for the
> future. With the success of the mouse atlas, he put another $100 million
> toward a tougher proposition, an atlas of the human brain, which is
> 3,000 times as big, with 1,000 times as many cells.
>
> All the equipment for slicing and staining the brains had to be
> refitted. And, more critically, the brains themselves were hard to
> acquire. Rather than 1,000 human brains, the map would have to be built
> with fewer than 10, which needed to come from people who had died in the
> prime of life without the brain being damaged by injury or illness.
>
> Four years later six brains have been donated and four analyzed to some
> degree. The project is due to be finished this year, but the first
> brain images, put online in 2010, are already yielding scientific
> results. So far, the gene expression from the first two human brains in
> the new atlas varies only a little, yielding hope that scientists will
> be able to understand some of what it all means.
>
> How might this work? A young University of California, San Francisco
> neuroscientist named Bradley Voytek used software to match words that
> frequently appeared together in the scientific literature with matches
> of where genes are expressed in the Allen atlas. For instance, he found
> that scientists studying serotonin, the neurotransmitter hit by Prozac
> and Zoloft, were ignoring two brain areas where the chemical was
> expressed in their research. It might even play a role in migraines.
> This data-driven approach led to 800 new ideas about how the brain may
> work that scientists can now test, leading to hope that computational
> methods can help decipher the computer in our heads.
>
> Understanding the brain, Allen argues, is much like a being a medieval
> blacksmith trying to reverse engineer a jet plane. It's not just
> that you don't understand how the wing attaches to the fuselage or
> what makes the engine go. You don't even know the basic theory of
> how air going over a wing creates lift. "Moore's Law-based
> technology is so much easier than neuroscience," Allen says.
> "The brain works in such a different way from the way a computer
> does. The computer is a very regular structure. It's very uniform.
> It's got a bunch of memory, and it's got a little element that
> computes bits of memory and combines them with each other and puts them
> back somewhere. It's a very simple thing.
>
> "So for someone to learn how to program a computer, in most cases, a
> human being can do it. You can start programming. I did it in high
> school. Me and Bill Gates and our friends did that. Probably in a few
> months we were programming and probably understood what there was to
> understand about computing within a few years of diving into it."
>
> In the human brain, designed by evolution, every tiny part is very
> different from every other tiny part. "It's hideously
> complex," Allen says. And it's going to take "decades and
> decades" of more research to understand. "We are talking about
> dozens and dozens of Nobel Prizes," he says, "that have yet to
> be won to understand how the brain works."
>
> Despite the size of the challenge, Allen is undeterred. Shifting from
> his army of pit-stopping young scientists, in the last 18 months he has
> hired three of the top neuroscientists in the countryand tripled
> the total head count at the institute to 200 with plans to double it
> yet again and move to a new, bigger building. Christof Koch of Caltech,
> a former physicist with an Apple Computer logo tattooed on his left
> arm, says his colleagues think that he is crazy to leave the safety of
> academic tenure, but there's no other way to get the job done. There
> are 10,000 neuroscience labs out there, but nobody else is trying to do
> anything as big. "We have ten-year plans to do something that
> can't be done at the university," he says.
>
> Clay Reid, who quit a tenured job at Harvard, studies the mouse visual
> cortex. "I can have big dreams about what to do next, but managing
> those would be just impossible anywhere else." This project, dubbed
> Mindscope, uses tools like the laser microscope that Allen saw for the
> first time when I met him to build a computer model of mouse vision.
> Colombian neuroscientist Ricardo Dolmetsch, on leave from Stanford,
> heads up another challenge: using stem cells to figure out what the
> brain is made of. "If a mechanic didn't know how many parts
> were in a car, would you trust that mechanic?" quips Koch, who
> likens current drugs for depression and schizophrenia to fixing that
> car by pouring oil over the top and hoping some gets into the motor.
>
> In rolling up all this talent, Allen, the consummate entrepreneur and
> outsider, has switched sides. Science, like the early days of software,
> has generally been practiced by hundreds or thousands of individual
> scientists working independently, competing to scoop one
> anothereven large-scale research labs like Salk and Rockefeller
> work this way. Allen's industrialized approach is known by
> researchers as "big science," a worrisome trend to some.
> "The state of funding in neuroscience is worse than it's ever
> been in my career," says NYU neuroscientist Tony Movshon. "I
> think small, investigator-initiated science is the best way to get
> creative ideas."
>
> It's possible that even the Human Genome Project that inspired Allen
> in the first place also slowed down the commercialization of
> DNA-sequencing technology, because it created a monopoly for machines
> made by one company, Applied Biosciences. Only after the project ended,
> and new, cheaper entrants entered the field, did we get a new revolution
> in genetics.
>
> "There are going to be things where you need to have the standards
> and you need to do something systematically on a big scale," shrugs
> Allan Jones, the Allen Institute's chief executive. "Small labs
> don't lend themselves to doing that well." In physics, he
> points out, it's standard practice to get everyone on the same page
> and do large projects like CERN's supercollider. There's no
> reason that mysteries of the mind should require less of a group effort
> than mysteries of the universe.
>
> Paul Allen is still more sanguine. "The proof will come a few years
> up the road, when we see the results of these new initiatives on which
> we are embarking now," he says. His $300 million investment was made
> with a five-year time horizon, but Allen and his team don't talk in
> five-year or even ten-year timethey're looking ahead decades.
> Allen, who says he feels great and is cancer free, says he will
> contribute indefinitely as his scientists continue to deliverand
> has even made plans to fund the institute after his death. "A big
> part of my own financial legacy," he says, "is allocated to
> this kind of work for the future."
>
>
> http://www.forbes.com/sites/matthewherper/2012/09/18/inside-paul-allens-\
> quest-to-reverse-engineer-the-brain/4/
> <http://www.forbes.com/sites/matthewherper/2012/09/18/inside-paul-allens\
> -quest-to-reverse-engineer-the-brain/4/>
>
