http://mitworld.mit.edu/ MIT World media in category 'Biotechnology'. en-us Tue, 24 Nov 2009 21:20:47 GMT Tue, 17 Feb 2009 00:00:00 -0500 http://mitworld.mit.edu/video/646 http://mitworld.mit.edu/video/646 Inspired by the vast potential of bioengineering, ordinary people are seeking their inner Frankenstein -- doctor, not monster. Two speakers who know their way around Petri dish and beaker discuss the possibilities and pitfalls of do-it-yourself biology with an MIT Museum crowd.

Showing ads from a 1980 Omni magazine, Natalie Kuldell reflects on the vast changes in computer engineering in the past few decades – from 20-lb PCs to laptops and handhelds. In contrast, she laments, genetic engineering today still resembles in large part its 1980 antecedents -- inserting bits of DNA into organisms like E. coli. She avers that computer engineering made such leaps because its technology was widely available to amateurs, who helped drive many advances. Biotech hasn’t moved as fast, and won’t, believes a nascent do-it-yourself (DIY) community, until basic components of biology become accessible to a larger population.

Synthetic biology aims to make new biological forms easier to engineer. Kuldell complains that “much of my time is spent doing things to do the experiments I need to do. It would be terrific not to have to build things in advance.” But building biological components and streamlining processes is difficult in biology, because biosystems are complex, and unpredictable. Can amateurs working with “Tupperware, thermometers and genetic engineering in the kitchen” discover “something remarkable doing their biology at home?”

Reshma Shetty thinks engineered organisms can do more than sense toxic metals in the environment or determine whether seawater is contaminated. She can “imagine a DIY bioengineer…doing something more fantastical, ambitious…. What about growing your own house?” Shetty describes a home experiment that can make bacteria smell like bananas. This is a small feat, but to achieve something significant, a real contribution to science, Shetty says DIY biologists need bio-engineered friendly organisms that will serve as common models, safe, easy to grow “and fun to use.” Candidates include moss, an easy to grow bacterium called Acinetobacter, and the salt-loving Halobacterium. By giving people the right tools, “they can build something fun and creative others can appreciate.” ]]> Tue, 22 Jul 2008 00:00:00 -0400 http://mitworld.mit.edu/video/579 http://mitworld.mit.edu/video/579 These two MIT Museum speakers hope you’ll walk away from their talk with a good case of augmentation envy – or at least a healthy respect for what technology can do for the human body and soul.

John Hockenberry has used a wheelchair for 30 years, since a car accident left him a paraplegic. He tells us the public has viewed spinal cord injuries like his as “something horrific,” or “staggeringly poignant.” But in the last 10 years, disability has moved from being “an extraordinarily fringe activity” to a central issue facing society, that of “marrying technology with humanity in a way that is organic to the body, appropriate to the spirit and sustainable to the community.” Hockenberry believes that the needs and demands of disabled people are helping push science toward creating a set of design principles “that will allow this issue of human restoration and augmentation to merge into a kind of seamless unity.”

In illustration of this claim, Hugh Herr describes the astonishing strides engineers are making in the development of “Human 2.0.” He starts with himself -- a victim of frostbite during a 1982 mountain climbing accident. After losing both feet below the knee, Herr headed for the machine shop, and realized he didn’t have to accept the version of his body provided by nature. So he cobbled together a pair of prostheses perfect for climbing (which made him over 7 feet tall), followed by other foot-ankle replacements made lightweight and responsive through carbon composite materials and computers. These designs are better than his originals, suggests Herr. “What’s fun about having part of your body artificial is that you can upgrade. It’s depressing to me, too bad that you folks have biological limbs.”

Wars in Iraq and Afghanistan have fueled the work in Herr’s lab. He’s now building robotic versions of arms and legs that restore capability, using computers and powered systems with sensors and motors. Stroke victims can use similar models, wrapped around an impaired limb, to restore symmetry between their left and right sides. The big prize will be a neural interface, a way of growing and reactivating an amputated nerve, so that it begins to convey sensory information through the complex networks of the brain. “The dream here is that one day I and other people with limb amputations will not only be able to walk across a sandy beach but feel the sand against their prosthesis,” says Herr.

Researchers haven’t imposed limits on their attempts at augmentation – or improvement. An MIT lab has designed a “socio-emotional prosthesis,” Herr tells us – using deep brain stimulators that leave subjects feeling “happy, calm, content.” Hockenberry wonders in conclusion whether we are “blowing away the notion of normal entirely and creating a completely improvisational notion of what it means to be human.” Herr proposes that in the future, “when we have many, many types of intimate technologies that are inside and attached to our bodies, it will unleash a renaissance in expression.” ]]> Wed, 23 Jan 2008 00:00:00 -0500 http://mitworld.mit.edu/video/518 http://mitworld.mit.edu/video/518 In 1845, the Dietz Company of New York introduced the sperm oil lantern, which nearly wiped out some whale species. A decade or so later, Dietz began to manufacture lamps using other oils, and gas lighting fixtures, giving whales a reprieve. More than a century has passed, and we’re “about to do it again,” says Daniel Nocera, consuming a precious resource and endangering this time not whales but our world. Nocera wonders, “What will be the savior,” the answer that will save the entire planet?

He ticks off the grim details of our fossil fuel habit -- how the world is rapidly moving from its energy consumption of 12.8 terawatts per year, to 28 terawatts by 2050. This is a simple calculation, Nocera tells us, requiring only population, GDP per capita and energy intensity. The upshot, unfortunately, is that though we do have enough carbon-based energy (oil, methane, coal) to last all of us quite a while, the CO2 we’re emitting may choke off our current way of life long before the end of the fuel.

Nocera advises his audience to put aside dreams that biomass or nuclear energy will give us what we need. Plaster the entire planet with crops we can convert to energy, and you’d still only get seven to 10 terawatts. And you’d “need one nuclear plant every 1.6 days for the next 45 years” to get eight terawatts of power. “There aren’t enough whales to get there in 45 years,” says Nocera.

His alternative for saving the planet is “far from pragmatism and reality.” Nocera’s ultimate solution seems almost magical: “water plus light equals oil.” The proposal is to emulate photosynthesis, the process by which plants convert the energy of sunlight to fuel. Scientists are racing to design structures that can catch light the way a leaf does, then capture the energy of this light using chemical bonds, and then somehow store this energy. Some researchers are focusing on photobiological water splitting. Nocera’s group is working “on a wireless current, an artificial leaf.” While the goal “is to see what nature’s structures tell you,” Nocera acknowledges that “if you try to place what’s in nature in a beaker, it probably won’t work.”

There’s massive urgency to working out the basic science of solar energy conversion. Forget 2050, says Nocera. “Science has got to get it done in the next 10 years, because it will take an enormous amount of time to implement". ]]> Thu, 27 Dec 2007 00:00:00 -0500 http://mitworld.mit.edu/video/511 http://mitworld.mit.edu/video/511 In the beginning, there was ENIAC. The first electrical computer could do 5,000 additions or subtractions per second, recounts Mark Reed, as long as people with shopping carts full of vacuum tubes jumped to the rescue each time the behemoth suffered a burnout. Then came transistors, and integrated circuits, greatly increasing the number of operations machines could perform, even as their components shrank. But now researchers face a serious barrier in miniaturization, called power dissipation.

As technologies scale down, and more computer chips get packed together, the number of watts per square centimeter reaches a point “when materials start to do nasty things, like break down,” says Reed. To break through the power dissipation barrier Reed and others look to biologically inspired systems. DNA could prove the ultimate scaffolding for new computational structures, believes Reed. He shows some examples of DNA folded like origami, and assembled into such patterns as stars, and even a map of the world. So why not create a simple component, like a switch? Researchers have fashioned RNA into just such a device, providing input signals via metal atoms, proteins, and other simple chemicals. They have even figured out how to send the signal from one artificial biological structure to another. This “is not far afield from the typical input/output of modern computers,” says Reed.

Scientists are developing a new generation of biosensors that can detect an electrical signal that might emanate from the smallest building blocks of life. Reed has developed “nanowires,” and applying etching techniques like those used for current semiconductors, fashioned biosensors that can detect minute changes in various biochemical environments. “Not only can we measure things like DNA and other proteins, but we can also talk to cells,” says Reed. The nanowire sensor has a future as a diagnostic tool, because it can read the biochemical messages cells send out when they’re sick -- in real time.

Eventually, Reed sees integrating complicated DNA structures with electronics that look like those found in our computers, and devising sensible interfaces to the biochemical world, “involving two-way communication with this environment.” Computation using such structures may start out slow, but massively parallel processing could bring speeds up without using a lot of power. ]]> Mon, 24 Sep 2007 00:00:00 -0400 http://mitworld.mit.edu/video/479 http://mitworld.mit.edu/video/479 Imagine a time when technology trumps injury and disease, and the very notion of disability begins to fade. These panelists suggest that we are at the dawn of such an era.

John Hockenberry, who zips around the stage in his flashing light –equipped wheelchair, tells us that “vast, extraordinary and sometimes frightening physical change can instead of being feared … actually be embraced and become an opportunity for people to take authorship of their own lives, using products and tools made by technology to make their life experiences better.” He sees an aging and longer-lived demographic necessitating new and better devices, and the likelihood that such tools may find broader use among a larger, able-bodied population.

Hugh Herr lost both legs below the knee to frostbite while hiking Mt. Washington in 1982. But his drive to climb compelled him to invent replacements that from his perspective far surpass the clumsy, skin-colored prostheses generally available. Herr demonstrates his biomechanical inventions, which provide not only a natural gait but additional energy to each stride – like an airport walkway, he says. Herr believes with some tweaking, his device could help stroke victims walk with better balance, and that the advantage conferred by such a device could make it desirable beyond the disabled population – think physical improvement by way of robotics, rather than steroids. As technology once intended exclusively for disabled people finds wider applications, there will be a transformation, says Herr, which “creates a world where there is not disability, but in fact augmentation. It makes it sexy. It’s the muscle car.”

Dean Kamen performs astonishing pirouettes in his iBOT, a device inspired by his desire to give wheelchair users the same view of the world taken for granted by those able to stand. This machine can give physically challenged people the independence to climb stairs, take a walk in the woods or at the beach.

Kamen also presents, through video clips, breathtaking developments in a robotic artificial arm – the result of U.S. government efforts to fast track (in two years!) a state-of-the-art prosthesis for victims of the conflicts in Iraq and Afghanistan. Nerve and muscle-sensing electrodes enable this arm to pick up small blocks, pieces of paper, and rotate at the wrist. Without government funding, this device would not have been developed, Kamen notes, due to market limitations. Kamen himself subsidizes development of other high tech tools for disabled people (his more lucrative day job involves making insulin pumps and stents). While he’d like these technologies to become “a killer app among people who can pay,” Kamen says, “We will continue to fund them with the naïve notion that it’s the right thing to do, and hope that we will meet our original objective of making the world a better place.” ]]> Wed, 01 Aug 2007 00:00:00 -0400 http://mitworld.mit.edu/video/468 http://mitworld.mit.edu/video/468 As urgency to address climate change mounts, there’s ever greater interest in harnessing the unlimited potential of the sun to replace fossil fuels. This tantalizing prospect has inspired a raft of new scientific ventures, reports Stephen Forrest.

A theoretical field of silicon solar cells that is 120 miles on one side and 120 miles on the other, plunked down in a temperate zone, has the capacity to generate 20 terawatts of power. While such a solar array could more than address the needs of today’s global population, the scheme is impractical and the costs prohibitive. Silicon is expensive, says Forrest. “On the world market today, if you put a gallon of gas in your car, you’re paying 10 times less money than if the same energy were supplied through solar, due to the materials, production, packaging, installation and storage cost.”

So scientists are exploring how organic materials -- not living cells, but carbon-containing compounds -- might make solar power more economical. Organic photovoltaic cells, made of thin layers of fluorescing molecules, seem to hold out hope of an inexpensive alternative to silicon. But so far, these cells don’t offer the same kind of power efficiency as silicon-based technologies. Organic materials tend to break down over time, and present challenges in terms of reproducibility, scalability and reliability. While researchers are trying to manipulate these materials so they function better, an organic photovoltaic device to rival silicon remains out of reach.

But there’s much more optimism surrounding organically based lighting materials. Keep in mind that interior lighting consumes 20% of the power used in buildings, notes Forrest. Replacing incandescent bulbs would make a great difference in residential and commercial energy usage. Current compact fluorescents have long operational lifetimes, but may not be the most satisfying to the human eye. Make way for organic light emitting diodes (OLEDs), using molecules that when excited give off extremely bright light. Researchers have found combinations of chemicals that mix blues, greens and reds in pleasing ways, and these displays will soon emerge in next generation handheld gadgets and computer screens. Researchers are experimenting with white OLEDs, which appear to exceed the power efficiencies of incandescents, and at a low cost as well. ]]> Mon, 04 Jun 2007 00:00:00 -0400 http://mitworld.mit.edu/video/451 http://mitworld.mit.edu/video/451 Though Stephen Quake’s research is confined to the smallest of scales, his achievements have already made a large impact on the study of biology. Quake’s area of microfluidics involves fabricating tiny devices akin to those a plumber uses, but useful on the molecular level. Quake modestly describes his “plumbing tools” as “very simple stuff, not rocket science,” but these mini valves and chambers, which enable him to manipulate the behaviors of fluids in minute volumes, are already proving useful in some of the toughest problems of bioscience.

Quake has fashioned microfluidic technology to analyze DNA sequences in a large-scale way, and to determine protein structure. Borrowing from computer engineering, Quake uses nanoliter amounts of fluids on chips in order to grow protein crystals. These new methods allow for much finer control and manipulation of protein crystal growth than conventional structural biology methods. His lab has figured out not only how to tie single DNA molecules into knots, but how to sequence them. Confronting the limits of conventional microscopy, Quake’s lab “stumbled upon the discovery of small colloidal particles that act as microlenses.” These tiny beads concentrate light and provide a “higher effective aperture, which works phenomenally well.” Now as they automate their miniature DNA and protein factories for mass production, they can observe their work in real time.
]]> Tue, 13 Feb 2007 00:00:00 -0500 http://mitworld.mit.edu/video/422 http://mitworld.mit.edu/video/422 Two of the sharpest minds in the computing arena spar gamely, but neither scores a knockdown in one of the oldest debates around: whether machines may someday achieve consciousness. (NB: Viewers may wish to brush up on the work of computer pioneer Alan Turing and philosopher John Searle in preparation for this video.)

Ray Kurzweil confidently states that artificial intelligence will, in the not distant future, “master human intelligence.” He cites the “exponential power of growth in technology” that will enable both a minute, detailed understanding of the human brain, and the capacity for building a machine that can at least simulate original thought. The “frontier” such a machine must cross is emotional intelligence—“being funny, expressing loving sentiment…” And when this occurs, says Kurzweil, it’s not entirely clear that the entity will have achieved consciousness, since we have no “consciousness detector” to determine if it is capable of subjective experiences.

Acknowledging that his position will prove unpopular, David Gelernter launches his attack: “We won’t even be able to build super-intelligent zombies unless we approach the problem right.” This means admitting that a continuum of cognitive styles exists among humans. As for building a conscious machine, he sees no possibility of one emerging from even the most sophisticated software. “Consciousness means the presence of mental states strictly private with no visible functions or consequences. A conscious entity can call on a thought or memory merely to feel happy, be inspired, soothed, feel anger…” Software programs, by definition, can be separated out, peeled away and run in a logically identical way on any computing platform. How could such a program spontaneously give rise to “a new node of consciousness?”

Kurzweil concedes the difficulty of defining consciousness, but does not want to wish away the concept, since it serves as the basis for our moral and ethical systems. He maintains his argument that reverse engineering of the human brain will enable machines that can act with a level of complexity, from which somehow consciousness will emerge.

Gelernter replies that believing this “seems a completely arbitrary claim. Anything might be true, but I don’t see what makes the claim plausible.” Ultimately, he says, Kurzweil must explain objectively and scientifically what consciousness is -- “how it’s created and got there.” Kurzweil stakes his claim on our future capacity to model digitally the actions of billions of neurons and neurotransmitters, which in humans somehow give rise to consciousness. Gelernter believes such a machine might simulate mental states, but not actually pass muster as a conscious entity. Ultimately, he questions the desirability of building such computers: “We might reach the state some day when we prefer the company of a robot from Walmart to our next-door neighbor or roommates.” ]]> Tue, 24 Oct 2006 00:00:00 -0400 http://mitworld.mit.edu/video/392 http://mitworld.mit.edu/video/392 No diagnosis of cancer is welcome, but some scenarios are more dreaded than others. Richard Hynes discusses what happens “when cells in the primary tumor lose their sense of address and wander off to places they’re not supposed to go.” His talk lays out the process of invasion, by which the cancer spreads into tissues adjacent to the tumor, and that of metastasis, where the cancer disseminates to distant sites.

Hynes describes the transitions a cancer undergoes as it spreads. He explains how tissue in our bodies is made of sheets of epithelial cells that are carefully arranged on a “basement membrane” by a series of adhesion receptors. These receptors, if functioning properly, don’t usually allow the cells to go anywhere. When a cell becomes tumorigenic, it loses some adhesion, and then if it becomes more damaged “wanders off into the underlying tissue.” This is called invasion. Hynes and other researchers are looking at the molecules responsible for cells’ adhesive qualities, and at the mutations in genes that trigger a loss of adhesion. Some of these processes are part of normal development, but occasionally, a “switch gets thrown in cells that should have stayed epithelial” and they become migratory instead.

Once on the move, cancer cells “need plumbing to grow,” says Hynes. Tumors recruit blood vessels to feed them and remove waste, and they can also exploit the body’s white blood cells and platelets to promote their own growth. Hynes describes “cross talk between tumor cells and cells in bone,” where the “two cells get together in evil combination to damage the bone and enhance the growth of metastases.” Scientists have discovered “a lot of different mechanisms by which metastatic cells learn new tricks and suborn the mechanism of the host to get them where they’re going.” Hynes finds such insidious workings an “appealing thing, since these alterations offer opportunities for therapies.” Researchers can tinker with circuits between cells, restore growth suppression and interfere with blood vessel recruitment. It’s “a complex problem,” says Hynes, but there are “lots of ways to get at this.” ]]> Wed, 11 Oct 2006 00:00:00 -0400 http://mitworld.mit.edu/video/388 http://mitworld.mit.edu/video/388 Since innovation is “not necessarily always predictable,” Daniel Vasella declines to discuss it in a systematic way, and instead, focuses on a case study of one of his company’s flagship pharmaceuticals, Gleevec. The discovery, development and marketing of this drug, which fights the rare chronic myeloid leukemia (CML), may point to some of the things Novartis does right, suggests Vasella.

Many significant drugs result from years of basic research that takes place outside of industry. Pathbreaking work that occurred decades ago uncovered chromosome damage in patients with CML, and revealed an abnormal protein secreted due to this mutation. In the early 1990s, Novartis began the creative work of trying to block the signal of this cancer-causing protein.

After testing numerous compounds, Gleevec was synthesized in 1992, and “then the problems started,” says Vasella. When the drug was delivered intravenously, there were toxic effects, and they couldn’t reproduce results from cell cultures. With 100 researchers laboring on the problem, recounts Vasella, “marketing said, ‘stop this damn thing.’”

Despite the setbacks, “We persisted,” says Vasella. Indeed, the first clinical human trials, on 31 patients, were so spectacular -- 100% remission rates -- that Vasella didn’t believe the data. The company moved into frenetic pitch to complete the additional clinical trials necessary for FDA approval, and then on to production. Employees volunteered to work in 24-hour shifts, seven days a week. Vasella faced another issue: “We had to come up with a way we’d make money,” since CML affected a relative handful of patients globally. And the fewer the patients, the higher the price of the drug, potentially keeping it out of the hands of those who most needed it. The company decided to subsidize the cost of Gleevec for patients of little means. In spite of this, Gleevec “has surpassed all expectations.” Sales this year alone will exceed $2.4 billion.

What elements might have led to this triumph and Novartis’ more recent successes? Vasella cites “intrinsic motivation” in each Novartis staff member, high standards, savvy risk-taking and persistence in both research and marketing, and a company culture that brings out the best in everyone.]]> Thu, 05 Oct 2006 00:00:00 -0400 http://mitworld.mit.edu/video/385 http://mitworld.mit.edu/video/385 This inaugural address lays the groundwork for an 11-part series on MIT’s efforts in cancer research. Susan Hockfield views MIT’s Center for Cancer Research as a central example of how “life sciences are coming into conversation with engineering in a powerful way.” Robert Silbey provides historical background on the notion of faculty ‘short courses’, and positions the Center as “the jewel in the crown of MIT, a spawning ground for scientific discovery and rewards.”

Tyler Jacks introduces the key research areas and scientists who will speak in the succeeding sessions. He offers a thumbnail sketch of cancer as a molecular genetic progression involving sequential alterations in, and the proliferation of, abnormal cells. “Think of a cancer cell like an integrated circuit: the same kinds of complexities in electronic networks also exist within cells,” notes Jacks. Because of work on the human genome, and advances in scientists’ ability to untangle these complex molecular interactions, “We now have the first generation of anti-cancer drugs targeted against molecular alterations in cancer,” says Jacks. Two highly successful drugs have already been derived from MIT research.

In addition, says Jacks, collaboration among biologists, engineers and mathematicians are yielding “a tremendous collection of tools and technologies.” These include tiny probes that enable diagnosis of cancers at earlier stages, nanoparticles that deliver a therapeutic payload directly to cancer cells, and devices that can be implanted in the body.]]> Tue, 19 Sep 2006 00:00:00 -0400 http://mitworld.mit.edu/video/379 http://mitworld.mit.edu/video/379 When Fiona Murray visited research centers in China recently, scientists greeted her quizzically: “People were baffled about what a business school professor was doing in stem cell and gene sequencing labs,” Murray says.

As it turns out, Murray’s tour was integral to her own MIT Sloan research exploring how science serves as a source of competitive advantage. As China and India and other developing countries produce scientists and engineers at a quickening pace, Murray hopes to find out if their capacity to capitalize on scientific ideas is expanding in a comparable way.

One challenge to this kind of research, says Murray, is that the market for scientific ideas “is poorly functioning.” Traditional markets, say for pork bellies, oil or diamonds have well-defined products, well-established metrics,” but how do you measure the quality of scientific ideas?

Murray’s solution is to visit key scientific and engineering institutes in other countries to observe both scientific infrastructure -- the physical state of laboratories -- and how researchers collaborate and generate useful knowledge. She also scans the scientific literature to see how many papers a particular country publishes, in what subdisciplines, and how many citations scientists receive.

Murray’s work may aid commercial enterprises intent on taking advantage of growing global scientific and engineering expertise. Some initial insights: places like China and India hold tremendous potential for firms, whether through their permissive regulatory climates or unique natural resources. But, she advises, don’t enter one of these countries expecting to hire scientists at bargain basement prices, since “the real costs of scientific labor are hidden.” Also, expect poor lab facilities, enormous bureaucracies and a crazy quilt of intellectual property and licensing rules.

Counsels Murray, “Start by collaborating on R&D with research institutes and labs. That allows you to understand their expertise, social rules of engagement and to potentially shape the rules.” ]]> Wed, 06 Sep 2006 00:00:00 -0400 http://mitworld.mit.edu/video/376 http://mitworld.mit.edu/video/376 Subra Suresh fleshes out the promise of nanotechnology, at least in regard to our understanding of disease. His talk, which focuses on malaria and its impact on red blood cells, demonstrates how the fields of engineering, biology and medicine are converging.

To function properly, he explains, a red blood cell -- eight micrometers in diameter or 1/10th the thickness of a human hair -- must be able to squeeze through three micrometer openings in blood vessels. Working with a “laser tweezer” and two tiny (nano-sized) glass beads, Suresh can apply pressure to stretch single cells so that they become thin enough to fit through small openings. He uses a computer to simulate in three dimensions how red blood cells might fold and lengthen under normal conditions in the human body.

With malaria, infected red blood cells lose their ability to stretch, and Suresh can measure precisely the degree of deformation. The parasite changes the molecular structure of the cell, which “becomes stiff and sticky,” unable to move through small blood vessels. So the spleen, which normally clears impurities from the body, can’t do its job, and the disease progresses.

With a global group of collaborators, Suresh is working on genetic manipulation of the malaria parasite to see how knocking out individual proteins might impact the structure of the infected cell. This kind of biomolecular measurement and manipulation may some day lead to new therapies for a disease that infects more than 400 million people per year.

Suresh is also applying nanotech approaches to other diseases. He is looking into how cancer cells “become less stiff, move more easily, leading to metastatic invasions.” This may ultimately prove useful in studying breast cancer, he says. ]]> Mon, 03 Jul 2006 00:00:00 -0400 http://mitworld.mit.edu/video/363 http://mitworld.mit.edu/video/363 There’s no mistaking Drew Endy’s profession: “I like to make things -- that’s what I do.” From his engineer’s perspective, the slow and painful methods of bioengineering demand a solution. Endy hopes to refine the tools necessary to move the field forward. “We’re going from looking at the living world as only coming from nature, to a subset of the living world being produced by engineers who design and build hopefully useful living artifacts according to our specifications,” says Endy.

Thirty years ago, scientists figured out how to use enzymes to cut and paste genetic material, leading to recombinant DNA technology. But the techniques involved are painfully slow, requiring very specific physical materials and “know-how via the guild-like structure of biology.” Endy points to methods coming on line that will make it easier to design and build biological systems.

One is DNA synthesis, in which a machine fed information and sugars generates a physical piece of DNA. It reminds Endy of the “matter compilers” seen on Star Trek, where “food materializes from a cubby in the wall.” This technique will allow the economical production of long sequences of DNA. Another key ingredient in bioengineering will be the development of standards for making and measuring DNA, in the same way that machining hardware came to be governed by common standards in the 19th century. Endy also suggests that biotechnology will be increasingly informed by useful abstraction, so that scientists will manipulate raw materials less and refined and repackaged materials more, in order to make new things simply and more reliably. These advances will also enable bioengineers to “be experts in our own domains without having to be masters of everything.”

But as bioengineering becomes easier, and “people start to engineer biology,” we’ll need to worry about new issues, says Endy: Will people synthesize pathogens from scratch? Will groups pool knowledge legally? Will there be accreditation and oversight of those who create biological systems?

]]> Fri, 07 Apr 2006 00:00:00 -0400 http://mitworld.mit.edu/video/341 http://mitworld.mit.edu/video/341 How do we distinguish our friends from foes? How does dementia destroy memory? And how can past experience invade the present with destructive force? Scientists are closing in on the biochemical roots of these neurological puzzles.

Thomas Insel describes the profound impact of a small group of neuropeptides on social behavior in animals, from worms to humans. Oxytocin, the hormone which turns on maternal behavior and cognition, turns out to play a large role in determining social memories. Mice whose genes for producing oxytocin are knocked out can’t seem to remember animals they’ve met 30 minutes earlier – what Insel describes as “dense social amnesia.” An area of the brain’s amygdala is particularly rich in oxytocin receptors, and when the peptide is injected into a nearby ventricle, the animals’ social interactions revert more closely to normal behavior. Oxytocin is a useful tool for interrogating the circuitry that enables humans to determine “who’s important to me, who I’d die for, who I’m pair-bonded with, who will take care of me,” says Insel.

Alzheimer’s Disease (AD), which afflicts 20 million people worldwide, begins by literally clogging and tangling the hippocampus, the part of the brain essential for learning and memory. Li-Huei Tsai and other researchers have found “compelling evidence” that a small protein may be critically important in activating AD’s awful atrophy of memory. By manipulating specific enzymes, Tsai has managed to model in animals “all the pathological hallmarks of Alzheimer’s Disease,” and zero in on the source of the plaques and tangles seen in human Alzheimer’s patients. Tsai foresees drug interventions that inhibit these enzymes. But, she says, a big task remains “even after we’re successful in halting a deleterious process--how can we restore learning and retrieve lost memory in AD patients?”

Why is it that only some people exposed to a shocking event develop post-traumatic stress disorder (PTSD)? Kerry Ressler’s research posits that some kind of learning must take place in the brain’s amygdala -- its fear response center—that cannot readily be extinguished. Researchers have tracked down a molecular factor that increases “after learning of fear or extinction of fear.” He believes that if this molecule is somehow blocked from doing its job, then someone suffering from PTSD cannot extinguish fear. In a fortuitous medical convergence, the drug D-cycloserine, which has been approved for years to treat tuberculosis, proves very effective in enhancing the effects of the molecule, and reducing fear of all kinds. One example: When people with fear of heights were given D-cycloserine as they took rides in elevators, they reported a significant, long-lasting reduction in their phobias. ]]> Sat, 05 Nov 2005 00:00:00 -0500 http://mitworld.mit.edu/video/301 http://mitworld.mit.edu/video/301 “To me, systems biology is the religion you switch to when target-based drug discovery doesn’t work,” Noubar Afeyan states boldly. He claims that after losing billions of dollars, the pharmaceutical industry and academia are beginning to see the value in testing drugs by measuring outcomes in biological networks. He calls this systems pharmacology, where you “measure in living systems multiple analytes in the same organism, perturbing the state and taking thousands of measurements per sample.” Researchers use computer images to visualize the differences and similarities in drug response across many networks, and then try to correlate these responses statistically.

The inability to predict toxicity early in drug development cost the pharmaceutical industry an astonishing $8 billion in 2003, says Joseph Bonventre, approximately one-third the cost of all drug failures. “We generally can’t pick up toxicity until it’s too late,” he says, so key challenges are developing better preclinical studies with useful biomarkers, improved animal models, and high throughput techniques; and on the clinical side, coming up with a “safe harbor approach to amass kidney and other toxicity data,” developing consortia to validate biomarkers, dealing with IP issues and building “an improved bedside to bench flow of information.”

Linda Griffith's vision is “building a human body on a chip.” She’s not talking about an individual’s genome or health history, but “a living, 3D interconnected set of tissues on a chip. If you perturb it, you make it develop a disease.” Such a device would enable researchers to predict negative drug interactions and even to build models of disease. Griffiths’ version of liver tissue, built on a silicon scaffold, may prove especially useful for drug toxicity tests.

At Biogen, “the holy grail for any justification of a new approach or technology is that we’re going to chop a significant amount off the time it takes to move a new product from bench to bedside,” says James Green. He believes that “drugs and paradigms are orders of magnitude more complicated than 24 years ago.” He hopes that new techniques “that take us into the genome, interpreting data as patterns” offer some promise. ]]> Fri, 21 Oct 2005 00:00:00 -0400 http://mitworld.mit.edu/video/296 http://mitworld.mit.edu/video/296 Genzyme is a leader in personalized medicine, as Mark Bamforth demonstrates. For instance, the company collects cartilage from a single patient, grows it in the lab, and sends it back securely to that same patient. The system, says Bamforth, tolerates “no mix ups.” But the company also deals in drugs sent to hundreds of thousands of kidney dialysis patients. Each kind of product must adhere to a specific kind of manufacturing and distribution process, and the regulations of the FDA and other countries. Bamforth must navigate “a complexity and diversity of supply chains.”

Peter Walsh works behind the scenes at UPS, making sure those brown trucks deliver to the right location at the right time. He believes that “healthcare is a good 20 to 30 years behind other industries” in terms of getting the goods from supplier to manufacturer to consumer. “We see in big pharma a silo approach. That needs to change … and means sharing of information—scary to think of in this industry.”

Abbott Weiss sees in pharmaceuticals “a highly fragmented set of supply chains” at a time when globalization poses increased risks, such as theft and diversion, and cost pressures. He describes working at Polaroid, and shipping out 120 million packs of film a year, with 140 countries each requiring different labeling. “Exception management is the rule in supply chains,” says Weiss. And unlike film, there are “life and death implications of getting the right medicine at the right time and right place.” The good news is that much of the technology for solving tracking and distribution problems already exists, Weiss says.

One such technology, radio frequency identification (RFID), is a good first enabling step for pharmaceutical makers, says Daniel Engels. “If I know what I have and where it is, I can do something about it.” The critical problem will be “asset visibility,” communicating this unique product information to suppliers and customers. And this kind of tagging will prove especially difficult for generic or bulk drugs, sent through distributors. The “end game” is information sharing.

]]> Thu, 13 Oct 2005 00:00:00 -0400 http://mitworld.mit.edu/video/294 http://mitworld.mit.edu/video/294 These panelists describe struggling to transform their approach to drug safety, while acknowledging the need to regain public trust after troubling episodes involving drug side effects.

Névine Zariffa points out that “no clinical trial program known to man will ever help predict every single instance of everything that might happen in the big, wide world.” But, she wonders, “What can we do better to link up what we discover through the clinical trial process relative to what happens in the real world?” One idea: a Center for Biomedical Information SWAT team to deal with FDA drug alerts.

“The whole country is moving slowly, but moving” toward capturing patient records, imaging information, and even genomic and proteomic data electronically, reports John Glaser. Partners HealthCare holds a clinical data repository for 3.3 million people, from academic medical centers to community hospitals. This kind of database may help track “consistent drug interactions” as well as notify patients at risk when a side effect becomes apparent.

“Even if you think that drug reviewers look at newspaper accounts, if they focus more on drug safety, wouldn’t that slow review times? The answer is no,” claims Randall Lutter. He says that the FDA has not slowed approval times to appease a worried public, nor has it sacrificed science to please manufacturers eager for rapid drug approval. Rather, the agency’s concerned with getting accurate warnings on drug packages at the time of their launch, and disseminating information earlier to the public.

In the early 60s, says Johanna Haas, when the use of Thalidomide was linked to terrible congenital deformities, legislation resulted that transformed the safety rules: “The onus shift(ed) to the company to prove the drug should be marketed, rather than to the FDA to prove it shouldn’t.” Now, a post-Vioxx paradigm is emerging, where drug makers are trying to track subtle side effects in enormous populations. The only answer is to set up databases running from the earliest clinical trials through the drug’s launch. “You take something that’s going to evolve over the course of years. You don’t want it forgotten and tucked into a clinical study report that’s forgotten until it emerges as a public policy issue later on and you say, ‘Hmm, curious.’” ]]> Mon, 25 Jul 2005 00:00:00 -0400 http://mitworld.mit.edu/video/278 http://mitworld.mit.edu/video/278 Glycomics, the study of sugars’ role in living systems, is a relative newcomer to the revolution in molecular biology. In fact, Ram Sasisekharan remembers how colleagues told him “not to work on carbohydrates -- that it was useless.” But his research has shown that glycans, observed as long chains or intricate branches of sugars on the surface of all cells, are significant players in the complex drama of cell growth, migration and death. Tracking down the function of sugars from their structure has turned out to be trickier than determining what protein a segment of DNA codes for. Sasisekharan likens it to “image processing, with six blind men and an elephant.” His team, deploying diverse analysis techniques, learned that sugars affect such properties of proteins as the ways in which they fold. Sasisekharan has also discovered that tumor cells contain sugar sequences that keep tumors dormant, or signal them to start dividing. He has found that pathogens such as viruses and bacteria bind to glycans. This opens the possibility for using glycans in subtle diagnostics as well as for “novel drug delivery strategies.”

Martha Gray provides some vignettes from the Division of Health Sciences and Technology (HST), demonstrating stunning advances in medical engineering. Leaping beyond RotoRooter methods for treating plugged blood vessels, HST researchers have developed stents for opening arteries that deliver drugs and function longer. And in a major breakthrough, scientists have managed to produce a polymer seeded with rat heart cells, and stimulate this living tissue to beat the way actual heart muscle does. Gray’s own research involves arthritis, and she describes new imaging techniques “that allow you to see things you didn’t see before,” including tiny defects in cartilage that may predict the emergence of joint disease. ]]> Sun, 24 Jul 2005 00:00:00 -0400 http://mitworld.mit.edu/video/277 http://mitworld.mit.edu/video/277 In Doug Lauffenburger’s view, MIT’s new bioengineering degree program is not merely justified, it is essential. Revolutionary changes in biological sciences—specifically, in molecular biology and genomics—have given scientists the means to understand and control both the building blocks and larger systems of living things. Now, says Lauffenburger, the “operation of biological functions needs to be understood in terms of biomolecular machines.” But the hard part, he says, is “predicting what happens when you manipulate them. It’s almost trial and error. That’s where engineering comes in.”

Linda Griffith provides one paradigm for such research. She is designing a scaffold on which to grow human cells for use in tissue implants. Using a “computer controlled process that builds complex 3D objects up from scratch,” Griffith creates a device that mimics the complex structures of joints and other body parts – suited for joint repair, or bone regeneration. Her research might someday produce organs for transplant. But Griffith’s grander goal involves “putting surgeons out of business,” by eliminating transplants altogether. She’s building a “liver on a chip” – growing liver cells on a tiny wafer with the architecture and molecular properties of actual liver cells. This biomechanical product can be used to test drug toxicity and gene therapies, and perhaps someday to model and block the growth of cancers.

Angela Belcher models her bioengineered devices on some of nature’s most ingenious products, such as the incredibly strong and exquisitely structured abalone shell. She designs on a nanoscale, getting viruses and antibodies to work with inorganic materials. “How far can you push organisms?” Belcher wonders. To date, she’s taught a nontoxic virus to recognize a specific metal used in a semiconductor wafer. Someday viruses could detect atomic defects in electronics. Belcher also describes virus scaffolds for growing semiconductor wires, and for generating lightweight batteries woven into soldier’s uniforms. She’s even looking into ways of spinning viruses, as spiders spin silk, for generating optical materials.

]]> Tue, 23 Nov 2004 00:00:00 -0500 http://mitworld.mit.edu/video/239 http://mitworld.mit.edu/video/239 Ignore the noisy debate around cloning, Rudolf Jaenisch quietly insists, and instead look closely at the biology involved. First, note that there are two different kinds of cloning: reproductive cloning, the attempt to create an exact replica of a human being, which Jaenisch believes to be both biologically flawed and morally questionable; and therapeutic cloning, which offers potential cures to some of mankind’s most devastating diseases, and from Jaenisch’s point of view, sidesteps ethical pitfalls. Both involve transferring the genetic material from a somatic cell (from the skin, for instance) into an individual egg cell. The fertilized cell gives rise to embryonic stem cells, which have the near miraculous capacity to differentiate into every kind of tissue found in the body. Jaenisch says human embryonic stem cell research could help reveal the mechanisms behind biological growth, and enable a customized approach to treating such diseases as diabetes and Parkinson’s. Once scientists create these ES cells, they can grow them in vitro.

Ethical problems emerge, Jaenisch believes, when a cloned embryo is implanted in a uterus with the intent of creating a full-term clone, or with the intent of harvesting stem cells from an aborted fetus. These involve the “destruction of potential life.” The creation of cloned ES cells for research purposes, however, is the “propagation of existing life,” says Jaenisch.

Stephen Marks delineates the various human rights arguments around cloning: Are we at risk “of turning people into products?” Can “we pursue genetic health and enhancements” while maintaining the individual’s dignity? He describes the U.S. administration’s current opposition to any form of cloning and in particular, its attempt to throttle international treaties that might eventually permit therapeutic cloning.]]> Thu, 04 Nov 2004 00:00:00 -0500 http://mitworld.mit.edu/video/235 http://mitworld.mit.edu/video/235 If the future once lay in plastics, as the film “The Graduate” claimed, today the watchword may be “feedstocks.” This term includes corn, wheat, soy, sunflower, rapeseed (canola)—the array of carbohydrates and proteins growing in fields across the planet. The news, as Douglas Cameron makes clear, is that these crops no longer serve just as staples for animal and human diets, but as the basis for a “revolution in the chemical industry.” Cameron’s company, Cargill, is exploring a host of biotech applications for carbohydrates, fats and proteins found in common crops. For instance, they’re attempting to convert a plastic derivative of lactic acid (derived from fermented starch) into inexpensive polymers for medical implants. Another application: polylactide fibers that not only give comfort to clothing but provide high wicking power. Cameron also sees soy and vegetable oils as a promising industrial “platform.” Cargill envisions transforming them for use in engines, as lubricants, hydraulic and transformer fluids, replacing environmentally unfriendly chemicals. If industry can find effective conversion methods, grains and legumes may emerge as primary sources of fuel, key ingredients in drugs and diet supplements, clothing and paper products, and as heightened versions of themselves—more nutritious food for people and animals.]]> Tue, 05 Oct 2004 00:00:00 -0400 http://mitworld.mit.edu/video/226 http://mitworld.mit.edu/video/226 Each speaker on this panel proposes a unique approach to the problem of making medicines universally affordable. Dr. David Meeker works in the area of rare diseases. Genzyme’s hormone replacement therapy for Gaucher disease, which affects roughly 30 thousand globally, costs $150k to $200k per year. For patients in nations with poor health care systems, Genzyme discounts the medicine steeply. “Don’t say free drugs,” says Meeker. “We’ll help individual patients as best we can but we’re going to work on developing a health care system in that country that will eventually be able to take over.”

At Avant Immunotherapeutics, Una Ryan’s company tackles new vaccines for travelers, bio-defense, global health and food safety uses. “We’re trying to making vaccines people will actually take: safe, effective, oral, single dose, rapid protection and no refrigeration.” There are enormous development costs involved, which are hard for a small company to shoulder, she says. Perhaps “all developed nations should pay their fair share for pharma R&D…and for developing countries’ drugs,” indexing drug prices to each nation’s GDP.

Patricia Danzon suggests that drug manufacturers sell “products to wholesalers at uniform prices worldwide, then negotiate confidential rebates with final purchasers... This way, the lower prices offered to lower income countries won’t spill over to higher income countries.” Hannah Kettler describes the Gates Foundation’s efforts to invest funds in public-private partnerships to reduce pharmaceutical RD costs. The foundation is also trying to build a fund to cover the costs of vaccinating in developing countries. Our expectation, she says, “is that if we pay the higher prices now, supply will expand and over time the price of vaccines will come down.”]]> Thu, 23 Sep 2004 00:00:00 -0400 http://mitworld.mit.edu/video/223 http://mitworld.mit.edu/video/223 The very first tablet or drop of a new medicine comes at a dear price-- $800 million – according to recent studies of R&D in pharmaceutical industries. But manufacturing subsequent pills costs literally pennies. What’s a fair way to price life-improving, or life-saving medicine? The two speakers in this part of the forum vigorously defend charging different prices for medicines in different parts of the world. Judy Lewent argues that differential pricing ensures global access. She says, “There would be little sense selling drugs at prices people can’t afford.” It also generates the revenues necessary to generate new cures. “When we price for access, it’s a reflection of our belief in the power of free markets to advance the social good. We can meet the world’s health needs and also make a profit and continue to prevent, treat and cure disease.” Mark McClellan sees on the horizon a new order of drug treatments, such as tailoring molecules to the needs of an individual patient. But, he says, we won’t reap the benefits of these potential cures if current trends continue: nations that band together to lower drug costs for their citizens, and the reimportation of brand name innovator drug products. McClellan says if we don’t “provide financial rewards that reflect the value of innovation, we may not continue to get improvements that biotech makes possible.” Both speakers endorse more affordable medicines, but through insurance coverage rather than price controls.]]> Mon, 07 Jun 2004 00:00:00 -0400 http://mitworld.mit.edu/video/203 http://mitworld.mit.edu/video/203 Out of a world population of 6 billion, 57 million people die each year. And while we have gained 20 years in life expectancy since World War 2, diseases like HIV have taken a toll on morbidity in many developing nations. But according to Rick Young, “the global disease burden is much larger than the number of deaths.” Countless millions suffer from cardiopulmonary diseases, cancer, and malaria, to name but a few, at a nearly incalculable cost to their families and society. Young’s mission is to attack the problem of global disease at the genetic level: he’s hunting for specific proteins that can turn the genetic machinery of diseases on, or off. These “gene regulators” can be knocked out of whack by a virus like HIV or by a mutation that results in a disease like mature onset diabetes. Young’s group has developed a DNA microarray technology that helps them link gene regulators to their corresponding genes. They’ve worked out the connections in yeast, and they’re targeting the human genome next. Young’s ultimate goal: “By continuing to focus on your 2000 gene regulators, we could eventually develop great insights into how organ systems work… (And) in all instances where disease is associated with misregulation, we could develop new strategies for drug development based on that.”]]> Thu, 29 Apr 2004 00:00:00 -0400 http://mitworld.mit.edu/video/195 http://mitworld.mit.edu/video/195 When disciplines converge, innovation results. To prove the point, two inventers offered rich and varied examples from their respective areas: artificial intelligence and biomedicine. Rodney Brooks describes robots exploring dangerous bunkers in Iraq and Afghanistan, and intelligent prosthetic limbs. He predicts that in a few decades, helper robots will be as prevalent as computers are today. Aging baby boomers, says Brooks, will insist on remaining in their own homes as long as possible. They’ll require high tech caretaking, as well as entertainment and education opportunities. Brooks believes that low-paid assisted living jobs, as well as agricultural and manufacturing work, will gradually migrate to smart machines. Robert Langer has a string of remarkable biomedical inventions to his credit. He tells us that not so long ago, sausage casing was used for dialysis tubing and mattress stuffing for breast implants. Langer turned the medical world on its head by creating new materials for clinical application: chemical compounds for skin grafts and for targeted cancer therapy. He has created an artificial scaffold for tissues and organs that may also help rebuild spinal cords. The latest research involves microchips that can deliver precise doses of drugs, and respond by remote control like a garage door opener.

]]> Sun, 11 Apr 2004 00:00:00 -0400 http://mitworld.mit.edu/video/190 http://mitworld.mit.edu/video/190 In this wide-ranging discussion, panelists seized on redesigning science education as a way of ensuring the success of systems biology. The first challenge lies in improving instruction in the earliest years. David Botstein said, “K-12 education has never been that great…(kids) don’t need to know everything in excruciating detail….Anything they find out by themselves is worth 10 or 20 of anything you tell them to do." Mark Kirschner remarked, “What’s left out is appropriate kinds of inquiry, and at the appropriate age.” Leroy Hood spoke with master teachers and “understood that the worst way to teach was lecture.” Another obstacle lies with the culture of higher education, where scientists are rewarded for focusing on a single specialty and for research, not teaching. George Poste pointed to “rampant egotism that’s destructive,” preventing collaboration. Peter Sorger commented, “Autonomy is given to faculty members in classroom. We need expectations. Students will gravitate to those courses that are taught well.” A major hurdle for budding systems biologists involves embracing a larger biology. Matt Scott spoke of building “excitement about things beautiful and mysterious.” Other panelists expressed hope that the diversity of living things would generate a passion not only to understand the fundamental interdependence among all living things but to preserve species as well. ]]> Thu, 11 Mar 2004 00:00:00 -0500 http://mitworld.mit.edu/video/183 http://mitworld.mit.edu/video/183 Very simply stated, systems biology attempts to “capture the dynamic nature of living systems.” To accomplish this, says Hood, you “have to bring together the flavors of biology, chemistry, computer science, engineering and physics,” among others. It’s a vast area to tackle. But with tools like the internet and digital DNA and protein sequencers on hand, it’s now possible to perform research aimed at unraveling the complex interaction of genes and environment in simple organisms.

Hood describes knocking out yeast cell genes, and turning off the machinery that metabolizes simple sugars. This sort of microscopic tampering allows scientists to build models of increasing complexity. A blueprint of gene regulation in sea urchins helped one scientist figure out a way to redesign the organism with two guts. But the ultimate prize is a deep understanding of human biology. Hood foresees a database—built with the help of nanotechnology — that categorizes and quantifies all proteins in the human genome. Scientists will be able to predict disease by detecting defective genes in blood samples, and then manipulate the genes to prevent the disease. “The integration of biology and medicine,” says Hood, “is where the rubber meets the road.”]]> Wed, 18 Feb 2004 00:00:00 -0500 http://mitworld.mit.edu/video/178 http://mitworld.mit.edu/video/178 According to David Page, “the Y chromosome is the Rodney Dangerfield of the human genome.” Regarded for 50 years as a genetic wasteland, the Y chromosome just doesn’t get any respect…until now. Page’s lab has made some startling discoveries that reverse the prevailing view.

Recall from basic biology that pairs of chromosomes exchange genetic material through a process of crossing over. This leads to genetic variation in offspring, and can weed out dangerous mutations. Although there’s limited gene swapping between the sex-determining X and Y chromosomes, the popular belief has been that a large portion of the Y could not recombine, and therefore will sooner or later self destruct. The long-term outlook for the Y chromosome was bleak.

But now there is hope and renewed respect for the Y. Page has found vast sequences of DNA on the Y that appear like palindromes (words like “mom” that read the same backwards and forwards). Page believes the two halves of the palindrome engage in a kind of crossing over. This can lead to repairing mutations, just as in ordinary chromosomes. Through this unique method, the Y chromosome not only endures but prevails. ]]> Sun, 16 Nov 2003 00:00:00 -0500 http://mitworld.mit.edu/video/161 http://mitworld.mit.edu/video/161 MIT research is helping to speed the diagnosis of disease, and easing our most common afflictions.

Dennis Freeman is working on a better hearing aid. He describes how our ears can perceive sounds that make the eardrum vibrate less than the diameter of a hydrogen atom. He envisions a computer chip that will emulate sensitive cells in our inner ear that both react to sounds and communicate them to the brain.

Martha Gray is developing methods to look inside joint tissue, at the molecular level, to diagnose arthritis early enough for useful therapies. An estimated one in three Americans suffer from this painful disease.

Fifty to 100 thousand people a year are killed by medical errors. Peter Szolovits imagines a computer health record devised and controlled by a patient over a lifetime, which could play a key role in avoiding mistakes in medical diagnosis and treatment.

Eric Grimson says the imaging techniques he’s developing will bring nothing short of a revolution in surgery. His animated, 3D models are strikingly successful at guiding surgeons before and during such high-wire acts as the removal of brain tumors. ]]>