PopSci’s 2nd Annual Brilliant 10

Next time you sit with a stranger at a dinner party, pray for someone as interesting as any of the scientists in the ranks of the second annual PopSci Brilliant 10. Someone who is well into an exciting career but still picking up speed. Someone in the grip of an obsessive inquiry into the nature of the world-brainy, resourceful, gutsy-and not afraid to talk about it. This year, we again sought researchers whose work, while watched and admired (and certainly envied) by colleagues, is largely unknown to a public that admits few scientists into the spotlight of fame.

One in this year’s group traveled East Africa cajoling people for blood samples, then processed the blood in a centrifuge she had jury-rigged to her Land Rover’s battery. Another vowed in junior high to defeat the disease that killed a friend–and may very well keep that promise. Many of the Brilliant 10 work in hybrid fields, because as the divisions between disciplines fade, that’s where the action is. They meld biology with engineering, computer science with ecology. Some work in fields so new–molecular anthropology, microfluidics–you’ve probably never heard of them.
This group is but a tiny cohort of the larger community of researchers doing the work that will reveal–and, by revealing, change–our world.

STEPHEN QUAKE

Microfluidics: CalTech

Building a computer from a plumber’s nightmare of miniature pipes.

Stephen Quake twirls between his fingers a transparent, rubbery square the size of a postage stamp. “You can make them out just barely,” he says, his eyes on its minuscule labyrinth of canals, each of which contains millionths of a raindrop’s worth of fluid. Quake is holding a miniature chemistry lab, in which pint-size beakers are replaced by channels the width of a human hair. A typical chip hosts a plumber’s nightmare of 1,000 chambers linked by some 3,500 valves. Here, by mixing tiny doses of chemicals in countless combinations, researchers can speedily puzzle out the blueprint of a human gene, or test thousands of variations of potential drug compounds to rapidly seek cures for diseases.

Quake, 34, is helping forge a new discipline: microfluidics. His chips have more than biological applications; they also work as computers. The
basic element of a computer is a bit–a 1 or 0 that stays as it is until the machine tells it to change. Writing in Science in May, Quake and colleagues unveiled a bit made of liquids. The bit is stored in a cell consisting of channels that meet at a four-way intersection. Clear fluid flows from the left, and blue fluid comes in from the right. The blue fluid contains polymers that stretch when the fluid passes through a nozzle at the intersection; the stretched polymers hang together, and as a result, the blue and clear fluids don’t mix. Instead, at the intersection the blue fluid goes one way–say, up–and the clear goes down. The scenario won’t change until something acts upon the fluids, so it represents a bit–say, a 1. To change that bit to a 0, Quake applies a pressure pulse. That disturbance forces the blue fluid down, switching the bit to a 0. Though Quake won’t be factoring large primes anytime soon, he has demonstrated that microscopic fluidic circuits are possible.

When Quake began, microfluidic chips were etched with difficulty into hard

silicon. He experimented with silicone and found it more suitable. His new chips possess thousands more channels than their silicon forebears, and 300 to 500 times more valves than his competitors’ chips. And they keep getting smaller. “One thing led to another,” he says, “and before you know it, we’d invented really powerful tools.”

–Charles Q. Choi

DEBORAH ESTRIN

Embedded Networks: UCLA

Her mini-networks track the forest and the trees–plus every leaf, bug, bird & dewdrop.

Deborah Estrin knows that when a tree falls in the forest, it always makes a sound. And by seeding the woods with miniature monitoring devices, she plans to make sure it will be heard. The director of a new $40 million UCLA research center for embedded networked sensing (ENS), Estrin, 43, wants to connect us to the physical world as intimately as the Internet connects us to one another. She envisions a future in which our surroundings will constantly take their own measure and report back. Bridges with sensors in their foundations will monitor their own structural health and detect the first tremors of an earthquake. Smart bandages will assess a patient’s medical condition. Dairy or wine manufacturers will be able to track the location and condition (including temperature) of shipments (see “The Mote Invasion”).

The building blocks of ENS are microprocessors the size of Matchbox cars that can be connected to a range of sensing devices–infrared cameras, acoustic and chemical sensors, motion detectors. The resultant devices are then scattered over a broad area to monitor the subtlest of changes. Data leapfrogs between processors, then streams to a central server. The biggest challenge for Estrin, a computer scientist, is managing the flood of information these networks will produce. She is devising algorithms that will enable the microprocessors to compress data, or to eliminate duplications before information is transmitted. She is also creating programs that will ensure data is transmitted only when it falls outside an established range–when, say, a leaf is wetter or the air warmer than expected. Other of her programs would restrict the very collection of data to times when it varies from the norm.

Estrin was already investigating ENS for security and other applications when in 1999 she vacationed in Costa Rica. The rain forest was so dense with life, she mused, it would be logistically impossible for biologists to track it all–but embedded sensors could. Last month, her center launched its first big ecosystem study–100 devices spread over 30 wooded acres near Palm Springs, California. Video cameras will watch bluebird nests, motion detectors will sense predators, and buried CO2 probes will monitor soil chemistry. The data will be broadcast on the Internet: www.jamesreserve.edu.

–Laurie Goldman

TEJAL DESAI

Tissue Engineering: Boston University

Pancreas, blood vessels or other organ on the fritz? She’ll build you a nifty replacement.

When Tejal Desai walked into professor Mauro Ferrari’s office at the University of California, Berkeley, she looked so young he mistook her for an overeager high schooler and almost threw her out. Undeterred, Desai told him she’d studied biomedical engineering as an undergrad at Brown and was seeking a challenging Ph.D. project. Ferrari assigned her a whopper: Build an implantable device that will eliminate the daily insulin injections diabetics give themselves to control blood sugar levels. Desai’s colleagues warned her the task was too hard, that she’d never graduate.

But after four years of coaxing cells to grow on chemically modified silicon surfaces, Desai had it: a microscopic device that, when implanted in diabetic rats, delivered ongoing, regular doses of insulin. The device functioned like a tiny tea strainer: A hollow bit of silicon perforated with tiny holes, it was filled with pancreas cells doing what pancreas cells do naturally–produce insulin. The holes were large enough for the insulin to diffuse out, but small enough that the pancreas cells stayed inside, and the rat’s immune agents–which would normally mark the cells as foreign and attack them–could not enter. “Nobody expects you to cure diabetes before you graduate,” recalls Ferrari. “And then Tejal did!” (For rats, anyway.)

Desai’s implant is being developed by a private company for human use, but Desai, now 31, has moved on. She has developed a speck-size layered plastic device that, when swallowed, attaches to the intestinal lining, releasing medicine. Next she plans to build better artificial blood vessels. The existing variety, mere tubes, cannot constrict or dilate as natural vessels do to control blood pressure. Desai’s goal is to make artificial vessels that coax the patient’s own body to grow replacements, then biodegrade, leaving the new natural vessels behind.

Desai’s father, a chemical engineer whose company designs water-desalination systems, cautioned her about engineering; it can be an unexciting profession, he told her. Then, in high school, Desai heard a biomedical
engineer speak. Here was a totally new incarnation of engineering, one packed with magical promise–building artificial organs, or artificial nerves for people with spinal cord injuries. Desai had found her calling. (Her father has since relented; they occasionally talk shop, especially on the topic of nanoporous membranes.) Says Kenneth Lutchen, chair of biomedical engineering at BU, “In 10 years, some promising young student will be labeled â€the next Tejal Desai.'”

–Martha Harbison

ERIK DEMAINE

Computational Origami: MIT

Paper folding as extreme mind-sport: pushing theoretical limits for the fun of it.

Erik Demaine was not your typical teenager. He went to college at 12, and by 14, he was a grad student at the University of Waterloo in Ontario, Canada. The work he did there sounds whimsical–making paper stars, angelfish and swans–but Demaine was confronting a thorny problem. Namely, which shapes can be made simply by folding a piece of paper, as many times as you like, then snipping off a corner and unfolding it. The answer, Demaine discovered, after two years of calculations and crumpled paper, is any shape you can think of. It is theoretically possible to create any two-dimensional straight-sided shape, from a triangle to the New York City skyline, with a single scissors cut.

That elegant theorem, completed in 1998, helped launch computational origami, a hybrid discipline–part computer science, part mathematics–that explores complex geometry concepts inspired by the Japanese art of paper folding. Demaine and a handful of colleagues pursue the mathematics of folding with the bravado of skateboarders. It is their extreme sport; they delight in the mysteries hidden within a simple sheet of paper. “Erik found a whole new pool of mathematical problems motivated by the field of origami,” says mathematician Joseph Mitchell of SUNY Stony Brook in New York. “These are the kinds of questions that turn us on.” Two years ago, at the ripe old age of 20, Demaine became an assistant professor at MIT.

The work has real-world value. Computational origami has helped engineers figure out how to unfold a telescope lens in outer space without damaging it, and determine the safest way to stow an airbag within a steering column. A grasp of the intricacies of folding could also help biologists understand proteins, the convoluted molecules that are prime actors in many diseases.

Home-schooled by his father, Demaine never had to distinguish between work and play. During his early years, the two traveled the U.S. by bus, stopping to live wherever they felt like it (Demaine’s parents divorced when he was young). When Erik was 7 and obsessed with Nintendo, his dad suggested he learn to create his own games; he was soon into computer programming. In college, he found the age gap little hindrance–when his friends repaired to a bar, he just ordered ginger ale.

Demaine keeps countless origami problems percolating in his head, but his research ranges far beyond: He has co-authored more than 100 papers on such topics as data structures, bio-informatics and the mathematical obstacles to winning at Tetris. He’s drawn to the unexpected: “You just look at something you normally see in a different way and think, Gee, I wonder if there’s some mathematics behind that?”

–Laurie Goldman

XIAOHUI FAN

Cosmology: University of Arizona, Tucson

By detecting faint galaxies, he peers deep within the universe to the start of time.

Xiaohui Fan’s astronomy career began in polluted downtown Beijing, where he used his high school’s rooftop telescopes to search for comets and flickering variable stars. But he wasn’t the romantic stargazer type, communing with infinity. He just wanted to see far. Really far. Some 15 years later and half a globe away, the 31-year-old University of Arizona astronomer now has regular access to the best telescopes in the world. He and his team on the Sloan Digital Sky Survey have already discovered 10 of the oldest objects in the cosmos–one of which, Fan’s best catch to date, sent its light our way nearly 13 billion years ago, a scant 800 million years after the big bang.

Back in 1995, while Fan was finishing his master’s degree in Beijing, he devised a new approach to searching for very distant quasars–incredibly bright, energetic galaxies with supermassive central black holes. The local facilities weren’t powerful enough, so he applied to Princeton University–Sloan headquarters. He essentially said, Here’s my plan, I need better equipment, and I’d really like to work with you. Before long, he was collaborating with hundreds of other scientists. “He knew everything about what we were doing before he even got here,” recalls Princeton astrophysicist Jeremiah Ostriker.

You can’t just pick a point in the sky, point your telescope, and expect to find a 12-plus-billion-year-old galaxy. That’s why Fan’s goals mesh so perfectly with Sloan, an exhaustive effort to map one-quarter of the visible universe. The 2.5-meter Sloan telescope isn’t adept at details, but it covers a huge swath of sky. Fan developed software that sifts through Sloan data, looking for the faint, reddish light that signifies a distant quasar, and whittles millions of objects down to a few hundred candidates.

By comparing Fan’s ancient quasars with newer ones, cosmologists hope to learn whether black holes evolve over time. The study of distant quasars may also help resolve a basic chicken-or-egg question: Are black holes a prerequisite or a product of galaxy formation? Fan contributes to theoretical research, but his long-term vision hasn’t changed. He wants to keep seeing really, really far. And that almost 13-billion-year-old quasar just isn’t good enough. “My goal would be to push it further,” he says, “to find the very first ones.”

–Gregory Mone

VICTOR VELCULESCU

Genomics: Johns Hopkins University

His maverick approach ushered in a new way to finger cancer genes.

Victor Velculescu’s office overlooks a building where physicians help patients battle tumors. Velculescu, 33, could work there himself–he got his M.D. concurrently with a Ph.D. in human genetics–but early on, he did the math and decided that though treating sick people would give him a hands-on role, he could help more people by discovering what makes cancer tick. Tumors arise from genetic errors in a single cell. The task he set himself was to find those glitchy genes.

One way to find genes is to extract all the DNA from a cell, then identify the individual genes contained within it. That’s the method the vaunted Human Genome Project (HGP) used. But though that approach reveals many of the genes within a cell, it doesn’t indicate what those genes do or when they are active. Velculescu decided that rather than identifying genes and then trying to figure out their role, he wanted to catch cancer genes in the act, and then identify them. He based his plan on a simple fact: All the active genes in a cell are copied into molecules of RNA. The more RNA copies, the more active the gene. If researchers could gather all the RNA molecules floating in a cancer cell and compare that collection to one from a normal cell, they could identify genes that are overactive in cancer–but working backward from RNA was slow. Velculescu theorized that by paring RNA molecules to the bare minimum and linking those pieces together, he could rapidly characterize and count each one. “It sounded too good to be true,” he recalls.

His method, known as SAGE, worked–and 30 times faster than the old one. SAGE was “revolutionary,” says Sanford Markowitz, a cancer geneticist at Case Western Reserve; it has so far identified dozens of genes involved in cancer and other diseases. Meanwhile, SAGE suggests the HGP may have vastly undercounted. But infighting ranks low in Velculescu’s concerns. “The goal,” he says, “is translating this information to ultimately help somebody.”

–JR Minkel

SAE WOO NAM

Quantum Cryptography: National Institute of Standards and Technology

He’s harnessed the bizarre quantum world and made it do his bidding.

A century after the discovery of quantum mechanics, physicists are still unsure what to make of it, but they are making things with it–machines that capitalize on particles’ weird ability to exist in two or more states at once, and their habit of freezing into a single state when observed. Sae Woo Nam, a 33-year-old physicist, recently built the world’s most sensitive photon detector. By interacting with the spooky quantum world, his device could make coded messages uncrackable.

When industry or government officials send a private
e-mail, they convert it to a string of 1’s and 0’s, then merge it with a string of random numbers. The result is so garbled, only someone possessing the random string can decode it. The random string is, therefore, the “key.” It is sent first–a transmission that must occur in total secrecy.

Scientists have long wanted to use photons to send secret keys, but until now the technology hasn’t been precise enough. Theoreti-cally, each 1 and 0 of the key could be encrypted on a single photon, then randomly polarized at some known angle–anywhere from straight up and down to perfectly flat. Eavesdropping would require intercepting the photons, copying them, then sending them on their way. Since due to quantum mechanics, it’s impossible to perfectly measure a photon’s polarization, an eavesdropper will find himself in a quandary: Unsure of the photons’ original states, he must guess when he retransmits them. His mistakes potentially alert the message’s recipient to the tampering. But recipients have lacked a way to assess incoming single photons, so they were effectively blind. Enter Nam. His device detects single photons by reading the faint heat pulses they generate in superconducting tungsten cooled to 1/10 of a degree above absolute zero. One might expect the maker of such a precise machine to be a cautious type. But Nam likes to dye his hair odd colors and has been known to enter a 200-mile bike race on the spur of the moment. His former adviser, Stanford physicist Blas Cabrera, says that, thanks to that energy, Nam does the work of three. “I like thinking about lots of random different things,” Nam says, most unprecisely.

–JR Minkel

BETTY PACE

Molecular Medicine: University of Texas, Dallas

Unlocking genetic on/off switches to fool the body into healing itself.

Growing up in Wisconsin, Betty Pace lost a good friend to sickle-cell anemia. Right then, in junior high, she decided to spend her life trying to find a cure. Now a physician and researcher, Pace, 49, may be closing in.

Sickle-cell anemia is caused by an error
in the gene that produces hemoglobin, the oxygen-carrying component of red blood cells. The defective hemoglobin molecules
form long, sticky polymers, making the blood cells sickle-shaped instead of round. These
abnormal cells clog up blood passageways; ultimately, vital organs are starved for oxygen. Diseases arising from a single faulty gene
are prime candidates for a treatment known as gene therapy: Just replace the faulty gene with the correct version, the thinking goes, and–voil!–a cure. The standard approach is to place the desired DNA in the shell of a neutralized virus and set it loose in the patient. But it’s tricky to get the desirable gene to insert itself correctly in the patient’s genetic machinery. In 30 years, gene therapy has partially cured only a few patients, and in 2002 two of the method’s poster children contracted leukemia as a result of their treatments. In January, the FDA suspended gene therapy trials in humans–making the field a troubled setting for a dedicated investigator like Pace.

But Pace’s approach sidesteps traditional gene therapy. Her work doesn’t involve shoehorning new DNA into cells but rather coaxing the body to heal itself. To counter sickle-cell anemia, she aims to
provoke the body to activate the fetal hemoglobin gene. This gene, which makes a protein that helps growing fetuses siphon the oxygen they need from their mother’s bloodstream, goes dormant at birth. What makes it of interest to Pace is that it never carries the sickling mutation, and if enough fetal hemoglobin is present in adult blood, sticky polymers will not form, even in the presence of mutated proteins made by the adult sickle-cell gene.

Pace searches for transcription factors–proteins that attach to the fetal hemoglobin gene and turn it on. This year she logged a major victory: She found one that, in cell culture at least, provides a promising boost in fetal hemoglobin production. Next, Pace will test it
in mice. Human trials are years off, but if she succeeds, doctors will
ultimately be able to remove stem cells from an afflicted person’s bone marrow, activate the gene, then return the cells to the patient, where they would produce the curative protein forever.

–Laura Fraser

MICHAEL MANGA

Geophysics: UC Berkeley

He models billion-year and minutes-long processes to grasp earth’s workings.

Michael Manga wants to understand planetary evolution, but he doesn’t have a few million years to sit around and observe. So he and his UC Berkeley colleagues have built a few Earths of their own. Ranging from cooler-size tanks of oil to 350-gallon vats of corn syrup, Manga’s model planets may not look quite right, but they do reveal geological processes. In one recent experiment, he and colleague Mark Jellinek simulated the life cycle of Earth’s hot spots–places where searing plumes of rock melt as they approach the Earth’s surface, spurring volcanic eruptions. Manga and Jellinek filled a small tank with a form of motor oil, then piped into the bottom of the tank a thin layer of soybean oil, which is denser. When they heated the mix from below, the soybean oil formed veins that rose to the surface, then dispersed. Manga and Jellinek had successfully compressed a
billion-year phenomenon into an hour.

Manga is so prolific, says former adviser Rick O’Connell, a Harvard professor of earth science, that he’s advancing not one area of geology but a dozen. Recently, Manga and grad student Helge Gonnermann disproved a long-held notion that when hot melted rock, or magma, rises quickly and breaks into pieces, it causes an explosive volcanic eruption. Manga and Gonnermann found the opposite is often true: Magma that breaks up as it shoots to the surface can prevent explosive eruptions. When magma rises fast, the surrounding pressure drops, allowing gas trapped in the magma to expand–much like carbon dioxide bubbles in a just-opened can of soda–and break up the
magma. Manga and Gonnermann found that sometimes the gas escapes from between the magma fragments and dissipates: Explosion avoided. This model has been confirmed by recent volcanic events, such as the eruption of Mount St. Helens.

Manga has his eye on Mars and Venus, and hopes future missions to those planets will unlock some of Earth’s mysteries–such as why Earth is the only local planet that has moving tectonic plates. He also plans to log more hours with the corn syrup. At 35, he certainly has the time.

–Gregory Mone

SARAH TISHKOFF

Molecular Anthropology: U. of Maryland, College Park

From the genes of living people, she divines the story of human origins.

Sarah Tishkoff realized how far she’d strayed from the scientific mainstream when she found herself processing blood samples in a centrifuge she’d hooked to the battery of her dusty Land Rover near a village in the Ngorongoro district of Tanzania. Tishkoff, 37, searches for human origins not by hunting for ancient skulls but by examining the “fossils” in our genome: genetic mutations that are passed down through the generations.

While still a student at Yale Medical School, Tishkoff developed a novel way to analyze DNA from living people’s blood. Then, by determining the frequency of mutations in DNA from various populations, she was able to conclude that African lineages are the oldest on Earth and that at some relatively recent time in the past, a small group of people migrated out of East Africa and populated the rest of the world. Her work buttressed the reigning theory of human origins that had been developed in the traditional fashion–by using
radioisotope dating to determine the ages of ancient
human bones found in Africa and elsewhere.

Tishkoff had few African DNA samples to work with, so in 2001 she headed into the bush to collect blood from as many tribal groups as possible. Map in hand, she spent days traveling between far-flung villages. At night she processed blood in her car-battery-operated centrifuge. She slept in a truckers’ guesthouse and was invited into the homes of Maasai herdspeople. She won over tribespeople and wary government officials. “It was the most exciting thing I’ve ever done,” she says. Tishkoff’s new database recently yielded a key insight: Several populations thought to have originated in northeastern Africa are ancient, dating back 90,000 years. This finding too reinforces traditional detective work into the origins of modern humans: Paleontologist Tim White of UC Berkeley reported in June that three Homo sapiens skulls found in Ethiopia are the oldest known.

–Laurie Goldman