Believes that combining different drugs could yield better ways to fight disease.
For decades, “drug discovery” has meant screening millions of compounds to find one that will block a disease process. But Alexis Borisy says that approach is too simplistic. Since “the body always uses mixtures of molecules to regulate itself,” he says, it makes sense to do the same when treating disease. In 2000 Borisy founded CombinatoRx in Boston to search for molecules already proven safe for humans but that combat disease only when used in combination. Along the way, he had to reinvent drug screening. While pharmaceutical companies typically ask only one question about each compound- does it have an effect?- CombinatoRx examines compounds two at a time, in different doses, answering that question 36 separate times. Borisy says the company had to create new lab processes and write software to analyze its masses of data. CombinatoRx has raised $60 million and has launched human trials of three drug combinations designed to treat cancer and rheumatoid arthritis. “Fifty years from now,” Borisy says, “a majority of drugs will be combination by design.”
Synthesized "biorubbers" that could replace damaged heart and lung tissue and rebuild blood vessels.
Guillermo Ameer is creating a set of high-tech tools to manage diverse medical conditions. “Most people in science tend to focus on one specific problem,” says the biomedical engineer, a native of Panama. His aim is broader: “I want to build things useful to people’s health.” His top tool to date is called biorubber: a rubber-band-like material that he helped invent during a postdoctoral fellowship. Stretchy, cheap, and biodegradable, biorubber could eventually be used to replace damaged heart or lung tissues. Ameer’s lab at Northwestern University is currently developing second-generation biorubbers with varying degrees of elasticity and degradation rates to act as scaffolds for engineered blood vessels or ligaments. While the assistant professor of biomedical engineering has two patents pending on that work, he has already received a patent for another innovation: a cartridge that uses genetically engineered antibodies to filter a protein called beta-2-microglobulin from the blood of kidney disease patients. Over time, this protein- which the traditional filters in dialysis machines don’t catch- can leave painful deposits in bones, joints, and tendons. Partly funded by the National Kidney Foundation and Baxter Healthcare, Ameer’s lab is refining the biofilter so clinical trials may be conducted- which means people could soon find out just how useful Ameer’s tools are.
Produces portable, inexpensive, microprocessor-size labs for research and industry.
With two degrees and three part-time jobs, Helene Andersson is bridging disciplines to build and market microprocessor-size laboratories. As Stockholm, Sweden-based startup Silex Microsystems, she serves as business manager and designs custom “labs-on-a-chip” for commercial uses ranging from bedside medical testing to detecting chemical and biological attacks. And the electrical engineer and molecular biotechnologist is exploring other applications in her work at Sweden’s Royal Institute of Technology and at Mesa+, a research institute in the Netherlands. As a doctoral student, Andersson developed production techniques for efficiently manufacturing the microlabs, and designed ever smaller pumps, valves, and other components for them. Several of her patented microstructures “boldly demonstrate to bioanalytical researchers the great advantages of microlabs,” says Mesa+ professor Albert van den Berg. These advantages include portability, speed, and economy. Andersson’s life is hectic, but she plans to continue all her pursuits. “It suits me very well,” she says, “to explore new things and learn how to do business with them at the same time.”
Uses microchip-manufacturing tools to build artificial livers.
In the United States alone, 17,000 people await liver transplants. Sangeeta Bhatia’s solution? Engineer a liver from scratch, using photopatterning techniques borrowed from the microchip industry. A completely functional artificial liver requires different types of cells arranged in complex patterns. The University of California, San Diego, associate professor of bioengineering and associate adjunct professor of medicine starts by mixing one type of liver cell with a liquid polymer and covering the mixture with a template. When ultraviolet light shines through the template, illuminated cells get trapped in the polymer; shaded cells can be washed away. By applying different templates and cell mixtures, Bhatia builds up layers that simulate the liver’s natural structure. Human trials remain years away, but meanwhile biotech firm Surface Logix is adapting her liver-cell work for drug research.
Aims to speed genome sequencing with a machine that reads DNA letter by letter.
Most biotech firms have their origins in labs, but Eugene Chan dreamed up U.S. Genomics in the medical-school dorms and libraries of Harvard University. His goal: to find a quicker, cheaper, more precise way to analyze DNA so all patients might benefit from the discoveries of the Human Genome Project. Chan patented his idea for a device that would read a DNA sequence straight from a single molecule- and left medical school in his second year to found U.S. Genomics in Woburn, MA, to develop the technology. The company’s latest prototypes catch fluorescence-tagged DNA on nanoscopic posts, unfurling the coiled molecules. The molecules then flow one by one into a narrow channel where lasers and optical detectors “read” the bar-code-like patterns created by the tags. The device can now identify certain sequences within long stretches of DNA; Chan hopes it will produce letter-by-letter sequences by 2006. He has raised some $57 million and recruited such sequencing gurus as Celera Genomics founder J. Craig Venter to the firm’s board. “The machines he’s built probably have hundreds of different applications,” Venter says.
Designs proteins from scratch to create new medicine.
As an undergraduate studying biomedical engineering, Bassil Dahiyat planned a career building medical devices. Pursuing a PhD at Caltech, however, he found himself working on much smaller structures; proteins. Indeed, Dahiyat designed the first completely artificial protein- a very simple one- by devising powerful algorithms that combine standard descriptions of the physical properties of protein molecules in novel ways. He then constructed the protein by chemically linking its amino acid building blocks. After graduating in 1997, Dahiyat founded Xencor and put his technology to work creating protein drugs. The Monrovia, CA, company has raised $65 million and plans next year to begin human trials of its first drug, an anti-inflammatory for treatment of rheumatoid arthritis, psoriasis, and Crohn’s disease. Today Xencor designs its drug candidates by “tweaking natural proteins,” says CEO Dahiyat, but he looks forward to computer models robust enough that he can design complex molecules from scratch, fulfilling his vision of completely artificial protein therapies. “The dream is to mimic how nature uses proteins- to essentially do any task you can imagine,” he says. “There’s this palette that we haven’t even started to paint with.”
Benjamin G. Davis
Manipulates biological sugars for more precise drug delivery.
Researchers have long known that proteins- pivotal players in everything from embryonic development to Alzheimer’s disease- often have sugars attached to them. But understanding precisely how those sugars influence the proteins’ functions was exceedingly difficult until the arrival of novel chemical reactions devised by University of Toronto postdoc Benjamin Davis. The reactions enabled Davis to add or substitute sugars on proteins with Lego-like ease- solving a problem that had stymied researchers for decades. Manipulating sugars could make it easier not only to systematically study the basic biology of proteins, but also to engineer them as drugs. Indeed, Davis is exploiting his techniques to create a drug delivery system in which different sugars direct protein-based drugs to target cells or organs. In November 2002, Davis who is now a lecturer at the University of Oxford, cofounded Glycoform in England to commercialize this and other work; within a week he obtained $2 million in venture funding. The company is now conducting trials of the drug delivery system and developing new sugar attachment techniques.
Develops fast, automated processes for figuring out genes functions.
When scientists discovered that short pieces of RNA can shut down specific genes- a phenomenon called “RNA interference”- they hailed the finding as “revolutionary.” As a postdoc in 1998, Christohe Echeverri co-led the first group to successfully test the use of RNA interference to shut down genes selectively across an entire genome. Such an approach could prove crucial to determining what the tens of thousands of genes in animal and human genomes actually do. Scientists had devised a few RNA-based methods for determining gene function, but they were too time-consuming to stride through a full genome, sometimes taking months to analyze a single gene. Echeverri helped lead a team that developed micromachinery, chemical reactions, and algorithms to automate the process and record its outcome. Echeverri says his team uncovered the roles of four to six genes per day. The triumph prompted Canadian-born Echeverri to cofound Dresden, Germany-based Centix BioScience in 1999; the 35-employee company has raised 11 million euros. In partnership with Austin, TX, biotech firm Ambion, Centix is developing the first commercially available human-genome-wide libraries of interfering RNA molecules„ which clients could use to find new drug targets.
Michael E. Gertner
Set out to improve the tiny devices that keep once blocked arteries open.
When Michael Gertner is convinced he’s right, it’s damn the torpedos, full speed ahead! A resident in general surgery at the University of California, San Francisco, Medical Center, Gertner pondered how to improve coatings for stents- tiny expandable structures that doctors implant to help hold coronary arteries open once they have been unblocked by angioplasty. Each year, more than 900,000 coronary stents are deployed in the U.S., and over time they can become covered with scar tissue that can once again impede blood flow. New stents are coated with polymers that, for a week or two, release a drug that inhibits scarring, but the polymers can degrade the drugs or even harm blood vessels. Gertner reasoned that a metal coating would work better. Ignoring some experts who doubted his approach’s commercial viability, he and a colleague developed a process for coating stents with metallic films. The metal forms a fine lattice that carries drug molecules it can release for up to six months. Although surgery keeps Gertner busy, he has cofounded Nanomedical Technologies in San Francisco to develop the system. A stent manufacturer has already acquired parts of the technology. Time will tell if those doubting experts were wrong.
Patented a lab-on-a-chip to investigate call proteins that cause diseases.
For Jay Groves, inspiration began with tweezers. As a graduate student, Groves was studying cell membranes- the fatty wrappers that enclose living cells- and the proteins that stud them. Though 80 percent of drugs work by binding to these proteins, they are poorly understood and hard to study. While trying to measure the motion of cell membrane proteins, Groves scratched the silica surface supporting them with his tweezers to help focus his microscope. He noticed that the molecules couldn’t move across the scratch- and a new idea was born. Could researchers create patterns on wafers that would, like the scratch, corral proteins? Sure enough, Groves developed and patented the MembraneChip, a silic surface etched with tiny squares that partition cell membrane proteins so they can be studied. In 2000 he launched a five-person biotech company, Proteomic Systems, now called Synamem, in Burlingame, CA, which licensed the MembraneChip to seek new drugs that suppress immune response or fight infection. Groves, who is now an assistant professor of chemistry at the University of California, Berkeley, says the technology could affect the study of autoimmune diseases, among other disorders. “Membranes are the definitive structural feature of life,” Groves says- and he is determined to master their ways.
Creates systems for delivering drugs to where theyre needed in the body.
After losing his grandmother to Cancer when he was 10, Justin Hanes vowed to combat the disease. Now a chemical engineer, he has already won his first battle, designing polymer aerosols that deliver drugs to the lungs. Inhaling medications spares patients from injections, and certain drugs are more effective when breathed in. Hanes and his coworkers devised a way to make coated polymer particles porous; the particles serve as drug-carrying vessels that are large enough to lower the odds of attack by the immune system, but light enough to stay aloft and reach deep inside the lungs. There the polymer degrades, releasing insulin, growth hormones, or asthma medications over hours, days or weeks. Hanes and his colleagues’ pioneering work provided the core technology for Advanced Inhalation Research, founded in Cambridge, MA, in 1997 and sold two years later for $114 million. Although Hanes received stock from the sale, he chose an academic career. Now an assistant professor at John Hopkins University, he is building a new polymer for transporting cancer drugs. Enzymes secreted by growing tumors destroy the new polymer, thus discharging drugs where they’re needed most. “Why spread poison over the whole yard to eliminate one weed?” Hanes asks.
Speeds protein evolution to improve detergents, medicines, and foods.
An admirer of Charles Darwin, Andre Koltermann is bent on speeding up natural evolution. Bacteria, for example, produce enzymes with useful stain-fighting properties, but nature has yet to make an enzyme that performs optimally alongside the harsh chemicals in laundry detergents. Andre Koltermann says his company, Direvo Biotech, has. Koltermann and his colleagues have altered an enzyme used in commercial detergents, making it a hundred times more effective at eliminating stains. They did so by adapting “directed evolution,” a technique for inducing the genes that encode the enzymes to mutate or recombine. Researchers use fluorescence spectroscopy to screen for promising variations. The process enabled Koltermann to find the best enzymes more quickly than is possible with conventional techniques. Founded in Cologne, Germany, in 2000 by Koltermann and two partners, Direvo has secured more than $25 million in financing. Koltermann will use the funds to expand the firm’s work in directed evolution, with the aim of improving the enzymes in medicines, foods and animal feeds.
Helped paralyzed rats walk again and aims to do the same for people.
A playwright who has written a one-act farce, Erin Lavik has a day job that is no laughing matter. She uses polymers and neural stem cells to promote recovery from spinal cord injuries, which 10,000 people suffer each year in the United States alone. A Yale University assistant professor of biomedical engineering, Lavik designed polymer scaffolds that mimic the architecture of a healthy spinal cord, seeded the scaffolds with neural stem cells, and implanted them in paralyzed rats. Much to everyone’s surprise, the rats were able to move their limbs, bear weight, and even walk. Although spinal cord injury research is a big field, Lavik’s method is the first to demonstrate such dramatic success. Repairing spinal cord injuries in humans will be a bigger challenge, but them, Lavik didn’t expect her injured rats to walk so soon. If she has her way, people with spinal cord injuries could be walking sooner than expected, too.
Maps gene variations that could warn of future disease.
Molecular biologist Xiangjun Liu wants to know whether something in your genes can predict your likelihood of contracting a debilitating disease. The human genome contains many small person-to-person variations called single-nucleotide polymorphisms (SNPs). SNPs are associated with a variety of diseases, but defining which combination of SNPs can predict the onset of a specific disease is a formidable task. As a researcher at Celera Genomics in Rockville, MD, Liu laid the groundwork for that effort by leading a team that sifted through billions of genetic sequences and produced a database of 2.8 million SNPs. Researchers worldwide are using these data to learn which genetic variations are involved in diseases and how those variations might affect drug efficacy and toxicity in different people. In February 2002 Liu returned to his native China to advance this work as director of Tsinghua University’s Bioinformatics Research Lab in Beijing. The lab is trying to pinpoint the SNPs associated with atherosclerosis and other ailments. Liu also heads a Chinese government project to analyze SNP findings worldwide. Ultimately, Liu hopes to identify people likely to develop a given disease, so doctors can work proactively to prescribe treatments that will prevent or minimize symptoms.
Packs insulin into gel pills that could replace injections for diabetes patients.
As a graduate student, Anthony Lowman faced a dilemma; pursue polymers or medicine. He chose both. Now a chemical engineering professor at Drexel University, Lowman specializes in hydrogels- versatile blends of gelatinous particles and water. Certain medications, such as insulin, cannot be taken orally because enzymes in the stomach break them down before they can be absorbed into the bloodstream. Lowman created a novel way of shielding insulin inside polymer-based hydrogels. The hydrogels have pores that can hold insulin and open only in response to the high pH of the upper small intestine; there, the insulin diffuses into surrounding tissue. The technology, now in animal testing, could enable patients with type 1 diabetes (more than a million in the United States) to take insulin-filled gel pills in lieu of injections. Lowman is researching a similar approach to delivering drugs for cancer, osteoporosis, and other conditions. In his part-time job as chief technical officer for Gelifex, a Philadelphia-based company he cofounded in 2002, Lowman is designing injectable hydrogels for repairing degenerative discs, the cause of back pain in five million Americans. He recently prepared a gel that could restore disc pressure and function. Clinical trials may begin in late 2004.
Unravels complex biological systems in his search for new drugs.
Biologists traditionally study organisms one gene or one protein at a time. But because organisms are collections of interwoven systems that involve interactions of many molecules, more and more researchers believe a systems-level approach to biology is critical for understanding diseases and developing cures. Gavin MacBeath is working on technology to facilitate that approach. An assistant professor in Harvard University’s chemistry and chemical biology department, MacBeath has found a way to attach thousands of functional protein samples to small glass chips. Using these chips, he can study more than 25,000 interactions between pairs of proteins in a single afternoon. He also plans to look for small molecules that can selectively disrupt interactions- both to learn more about basic biology and to identify potential drugs. In 2000, MacBeath cofounded Merrimack Pharmaceuticals in Cambridge, MA, to use systems biology to improve research on afflictions such as cancer. “This kind of work is going to change the way we discover drugs,” he says.
Uses light to help make diagnosing breast cancer and cervical cancer faster, more accurate and less invasive.
Do I have cancer? Is my unborn child in trouble? University of Wisconsin- Madison biomedical engineer Nimmi Ramanujam believes that the millions of women who face these questions each year deserve more accurate answers than those afforded by today’s diagnostic technologies. Consider breast biopsies. Doctors sometimes miss the tumor cells they’re trying to sample, so Ramanujam has developed a device that can help guide a biopsy needle to just the right spot. An optical fiber threaded through the needle shines light of different wavelengths on cells as the needle’s tip; molecules in cancer cells respond by fluorescing in characteristic ways, and sensors register the fluorescence. Ramanujam and her colleagues are already testing the technology in patients undergoing breast cancer surgery and plan to test it in patients undergoing breast biopsy within the next year. A cervical-cancer detector she began developing as a graduate student uses a similar approach; it is now in large-scale human trials. Ramanujam is also harnessing light to non-invasively monitor how well oxygen is getting to fetuses, an important- and currently un-measurable- indicator of when emergency cesarean sections are needed. With Ramanujam’s help, those babies will be born into a world where medical questions get better answers.
Builds tiny machines that can warn of impending heart attack and monitor healing after surgery.
As a graduate student, Shuvo Roy developed microelectromechanical systems (MEMS)- tiny machines like sensors and actuators- for airplane and rocket engines. He had an aerospace job lined up, but inspired by his father, a public-health physiciain, he wanted to “impact people’s lives more directly.” The Bangladesh native switched career paths in 1998, cofounding a laboratory at Ohio’s Cleveland Clinic Foundation devoted to clinical applications of MEMS. Roy’s efforts have yielded several innovative devices and one patent- with several others pending. Among his inventions is a wireless strain and pressure microsensor that can be inserted into vertebrae during spinal fusion surgery (A main surgical option for back patients) to monitor bone fusion. Additionally, Roy shrunk ultrasound imaging technology into a high-resolution transducer small enough to glide through arteries on a catheter; the device can spot arterial defects called vulnerable plaques, considered the leading cause of heart attacks. Roy also developed durable silicon membranes that could replace short-lived polymers as blood filters in dialysis machines- a step toward creating implantable artificial kidneys. “Shuvo doesn’t care about recognition,” says lab codirector Aaron Fleischman. “He just wants to get technology that can help people into the hands of doctors.”
Wrote algorithms that can predict the functions of proteins from the sequence of a genome.
Since before University of Washington assistant professor Ram Samudrala was born, scientists have been striving to predict from an organism’s DNA sequence the identities and workings of its many proteins. Such an understanding could lead to improved treatments for diseases, which are often caused by malfunctioning proteins. Samudrala has advanced protein encoded by an organism’s genome. By modeling changes to specific genes or proteins, researchers can try to determine what causes proteins to go awry. One set of algorithms Samudrala devised, with $4 million from federal and private agencies, is called Bioverse. Samudrala has used Bioverse to model the functions and interactions of the proteins of more than 30 organisms; other researchers are using Bioverse to find which proteins in pathogens would be good targets for new drugs. Posted on the Web, Bioverse receives 1,000 hits daily. Samudrala made the algorithms free because he is opposed to intellectual-property restrictions, as explained in his “Free Music Philosophy” statement, which he published on the Web in 1994- long before the rise of Napster.
Transforms microbes into fine-tuned manufacturing machines.
When he was just 26, bioengineer Christophe Schilling won a small-business grant from the National Science Foundation. His plan was to reengineer the genomes of microorganisms such as bacteria and yeast, which are used as living chemical factories, to produce new or better products. With his university mentor, Bernhard Palsson, Schilling raised $3 million to launch Genomatica in San Diego in 2000. Today, the company is attracting partners such as Dow Chemical that want to engineer microbes to churn out chemicals used to make everything from drugs to soaps. Although that goal is not unique, Genomatica’s tool is: software dubbed SimPheny that decodes a microorganism’s genome data into a “pars list” of molecular components and enables the construction of computer models of the microbe’s metabolism. Corporate clients can then tap the models to predict a particular organism’s industrial potential. Genomatica also plans to release the software to select university labs by 2004.
Sheds light on the functioning of individual brain cells.
By combining physics, neuroscience, and optics, Mark Schnitzer intends to directly observe single neurons deep below the surface of the living mammalian brian; it would be a scientific first. While working at Lucent Technologies’ Bell Labs, Schnizer crafter an incredibly small endoscope- a fiber-optic viewing device with lenses as small as 350 micrometers across. The scope illuminates brain cells that have been labeled with a fluorescent dye; detectors in the device pick up the fluorescence and software constructs images of the cells. The device could allow neuroscientists to see how brain cells function, grow, and communicate across time synaptic gaps. Already, researchers are preparing to use Schnizer’s tool to study how animals store long-term memories. Because it is so small, the endoscope could also be fed deep into the brain, inflicting minimal harm on surrounding neurons. Human trials are years away, but Schnitzer says eventually his tool may help doctors detect brain cancers and blood clots without biopsy. Now an assistant professor in Stanford University’s departments of applied physics and biological sciences, Schnitzer continues to apply his tools to brain research.
Connects brains directly to computers int he hope of helping paralyzed people communicate and control robotic aids.
It takes incredible patience to interview people so severely paralyzed they can communicate only with the blink of an eye or the twitch of a brow. But it was partly impatience that inspired Mijail Serruya to do just that. The Brown University medical student and PhD was helping to develop a “brain-machine interface,” and he was eager to put it to work helping profoundly disabled people. Talking to them about their needs was an important step. Brain-machine interfaces could potentially allow paralyzed people to communicate through computers and to control robotic wheelchairs and aids. Serruya started by fine-tuning algorithms that allow signals recorded by electrode arrays implanted in the brain to change the position of a cursor on a computer screen. He says his colleagues were planning to explore human applications “one day”, but to him the question was, What are they waiting for? Aiming to move the interface into human trials, Serruya, Brown neuroscientist John Donoghue, and two others founded Foxborough, MA-based Cyberkinetics in 2001. They have hurdles to clear before they can begin human tests, Serruya says, but one gets the sense that all they need is a little patience.
Transforms research from universities and national labs into successful startups.
Thomas Edison and Eli Whitney are Micah Siegel’s idols- not just because they were great inventors, but because they turned their inventions into revolutionary products. “Ninety percent of the rewards go to the guy who figures out how to scale up what he is doing,” says Siegel. He earned PhDs in electrical engineering and molecular biology at Caltech, where he codeveloped genetically engineered sensors that change colors whenever a neuron’s functions are excited or inhibited. Twenty pharmaceutical labs are now using the sensors to test drugs. Business success excited Siegel’s own neurons, so in 2000 he cofounded Concept2Company in Palo Alto, CA, to help other scientists commercialize research. Since then, he has evaluated more than 350 business proposals from university and national labs and has raised millions of dollars on investments in several startups. In some deals, C2C steps in and handles the “business functions” many scientists hate- attracting management teams, licensing patents, schmoozing customers, raising capital- improving researchers’ chances or becoming Edisons or Whitneys.
Came up with a noninvasive alternative to colonoscopy.
A colonoscopy is the best way to diagnose colon cancer, but it’s so inconvenient and unpleasant that less than 25 percent of the at-risk population ever have one. The main alternative, a test for traces of blood in a stool sample, generates a high percentage of false positives. So Giovanni Traverso, a staff researcher at John Hopkins University’s Kimmel Cancer Center, set out to develop a convenient gene-based stool test that would reliably detect colon cancer at its earliest stages- when it’s still curable. Traverso had to develop sophisticated methods for isolating minute amounts of relevant DNA from feces samples patients collect at home, as well as a novel means of finding cancer-causing mutations in the DNA. In an early study, the test generated no false positives, but it didn’t detect all cancers. Traverso and colleagues are working to automate the test and boost its sensitivity; he’s also about to resume medical school in England. With luck, as a doctor, he’ll be able to get patients to take a colon cancer tests that could save lives.
Wants to make treating diabetes as easy as breathing.
Drug firms are vying to create the first inhaled version of insulin, which could deliver therapy more simply and effectively than needles to millions of diabetics. Rita Vanbever’s work might give Eli Lilly the edge. An associate professor of pharmaceutical technology at the Catholic University of Louvain in Belgium, Vanbever provided much of the chemical expertise that les to low-toxicity porous aerosol particles that carry insulin deep into the lungs. The particles do not clump, as earlier, smaller, and denser particles did, and they can be used with both fast-acting and long-actibg drugs. Cambridge, MA, drug firm Alkermes has licensed Vanbever’s techniques and is using them in partnership with Eli Lilly to develop inhaled human growth hormone in addition to insulin. Barriers remain; Vanbever discovered that human immune cells known as macrophages in the lung’s air sacs prevent up to 50 percent of such protein therapeutics from being absorbed into the bloodstream. But she is confident that her delivery methods will ultimately shrink that percentage significantly.
Programs living cells to sense toxins ot create replacement tissues.
Ron Weiss likes to give orders. In his lab at Princeton University, the assistant professor of electrical engineering sets the conversation and dictates the action. His charges, however, are not students but cells. Weiss builds synthetic DNA circuits- strings of genes that operate much like the logic circuits of computers- and injects them into E. coli bacteria, where they direct cell behavior. His goal? Create networks of different cells that work together to sense environmental toxins, generate new tissue, or perform other jobs. Collaborating with researchers at Princeton and Caltech, Weiss shares almost $6 million in grants, much of it from the U.S. Defense Advanced Research Projects Agency. In one of his projects, Weiss leads a multiple laboratory effort to program groups of cells to act as biological sentinels. Such systems could detect and pinpoint the locations of anthrax or other biological weapons. In another project, Weiss is devising faster, more reliable ways to direct stem cells to create new tissues to replace those lost to disease or injury- which means that one day a doctor might be able to order your own cells to heal you.
Synthesizes blood vessels that could reduce the trauma of heart surgery.
Every year more than 500,000 U.S. residents undergo coronary-artery bypass surgery. Soon, thanks to Rice University associate professor of bioengineering Jennifer West, that procedure may be less painful. To create a bypass, doctors must harvest a blood vessel- usually from the patient’s leg. West, however is growing vessels in the lab. She starts by synthesizing polymers that contain biological signaling molecules, the same molecules that guide tissue growth in the body. She molds the synthetic polymers into a blood-vessel-shaped template that is then seeded with three different types of live cells; by optimizing the polymers for different regions of the template, she can recreate the architecture of a natural vessel. The signaling molecules direct the cells to form new tissue, and the polymer support degrades in response. Human tests of the technology could start in five to 10 years, West says. Meanwhile, other heart patients might benefit from another West innovation: a polymer that could be used to coat an artery after angioplasty to prevent new blockages from forming. And West’s innovations address more than heart disease. She cofounded Nanospectra Biosciences in Houston to develop a cancer therapy based on gold nanoparticles that destroy tumor cells.
Spots promising biotech work and helps build new companies to commercialize it.
Daphne Zohar is a serial entrepreneur who is comfortable moving into almost any niche. She began by launching a successful olive oil brand. Then she pitched her patented “hoofpad”- basically, a sneaker fro racehorses- to veterinarians. Today she is forging biotech startups. The daughter of a Massachusetts General Hospital researcher, Zohar grew up around labs and has become good at recognizing commercial potential in lab work that night be otherwise unexplored. She is founder and CEO of Boston-based PureTech Ventures, which evaluates 15 ideas a week and chooses three each year to build businesses around. “Being an entrepreneur is like solving a puzzle with most of the pieces missing,” she says. PureTech’s stable includes companies making chips that rapidly analyze proteins, ultrasensitive antibodytests to screen blood banks for infectious agents, and nanoscale drug delivery systems targeting lymph nodes to treat cancer and HIV. Zohar’s team and advisors at PureTech include former Pharmacia and Upjohn CEO John Zabriskie and financier Todd Dagres of Battery Ventures, which manages $1.8 billion in capital. “I look for vision, determination, and entrepreneurial spirit,” Dagres says. “Daphne possesses all those traits.”