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In the world of biomedical research, basic science is usually held in the highest regard, while applied research is often looked down upon as mere “tool building.” But don’t tell that to this year’s TR100 honorees in biotechnology and medicine, a group intent on turning recent biomedical advances into practical technologies with an immediate impact. 

These researchers and entrepreneurs work in wildly divergent fields, from nanoengineering to “programming” living cells. Not surprisingly, they hold a range of opinions on which approaches and developments in biology are the most important and on how new technologies will affect our lives. Yet they share a desire to find real-life applications for their technologies as soon as possible. They also share an awareness that the convergence of biology and medicine with fields such as physics, engineering, computer science, materials science, and nanotechnology is yielding powerful new ways to help them achieve their ambitions.

Take Eugene Chan. Even as an undergraduate at Harvard University, Chan was intrigued by the Human Genome Project, the international effort to determine our genetic blueprint. But Chan also appreciated that the project’s true promise would only be realized when the technology was available to obtain full genetic information on individuals-prohibitively expensive and time consuming with the sequencing methods used in the Human Genome Project. “With all these wonderful [genetic] discoveries in the past 50 years, it’s now time to translate that from a research basis to a practical reality for each and every one of us,” Chan says. To usher in that reality, Chan quit medical school and founded Woburn, MA-based U.S. Genomics. He hired biologists, physicists, nanotechnologists, and informaticists, each of whom plays a role in realizing his vision: a machine capable of reading an entire human genome in 10 minutes.

That ambition to improve lives characterizes many of the TR100. Rice University bioengineer Jennifer West says that making a difference to patients is “one of the nicest things to see.” West is developing new materials for both treating cancer and engineering replacement tissues in the body. West and her colleagues at Rice found that by attaching particular proteins to tiny, hollow gold nanoparticles, called nanoshells, they could selectively target and destroy tumor cells. As a cofounder of Houston-based Nanospectra Biosciences, West is now helping to develop the nanoshells for cancer therapy. Here’s how it might work: A doctor injects the materials intravenously and waits an hour for the nanoparticles to find the cancerous cells. When the doctor shines infrared light on the patient, the nanoshells heat up and destroy only the tumor tissue. West believes that interdisciplinary research like hers, which combines advances in biology, medicine, and nanotechnology, will yield tremendous opportunities to create new treatments. “That’s where a lot of the successes will come from,” she says.

The juncture of biology and computer science is another promising area of convergence. Princeton University electrical engineer Ron Weiss is undertaking the ambitious task of “programming” living cells, encoding instructions using genes rather than the 1s and 0s he used when programming computers. As a postdoc at MIT, Weiss was looking to biology to inspire new methods of computer programming. “At some point I said, Instead of just staring at things on the screen, I really want to program cells.’” He hopes soon to begin programming tissue-specific human stem cells, instructing them on how to become different types of cells and, eventually, whole organs.

Weiss also foresees ultrarealistic computational simulations of cells or even humans that will be able to predict precisely what will happen as environmental conditions change or as foods or medicines are consumed. “Once we have that predictive power, that’s the point where progress is really going to increase,” he says.

Such dramatic dissolution of the boundaries between biology and computer science will take years. But other frontiers have already blurred enough to yield new technologies unimaginable a short time ago-such as Nimmi Ramanujam’s optical method of cancer diagnosis. The University of Wisconsin-Madison biomedical engineer studies how light interacts with human tissue and the characteristic changes cancers introduce to those interactions. Her efforts have yielded a noninvasive test for cervical cancer that is already in human trials. She’s now working on a breast cancer test that could be an aid to expensive and often inaccurate breast biopsies. The goal, she says, is to develop methods that can identify cancer at its earliest stages with very high accuracy and in real time-which would be a boon to thousands of cancer patients.

Pioneering work like Ramanujam’s is only the beginning of the transformation the TR100 honorees believe the accelerating pace of biomedical discovery will yield. Such rapid increases in knowledge, coupled with the new tools resulting from advances in areas such as nanotechnology and computer science, have led some in the TR100 to confidently predict that a “golden age” in biological science is emerging. “As we’re getting more and more information from things like genomics and proteomics, we’re gaining the ability to manipulate biology and do lots of new and exciting things with it,” says West. “Up to this point, we just didn’t know enough to understand how to make these things happen.” Armed with the new technologies and this new knowledge, the researchers you’ll meet in the next few pages are now intent on making their ambitious goals happen.

TR100 Startups in Biotech and Medicine
INNOVATOR COMPANY FOUNDED/COFOUNDED STRATEGY/MILESTONES
Alexis Borisy CombinatoRx (Boston, MA) New medicines generated by combining drugs; drugs for cancer and rheumatoid arthritis in human trials; has raised $60 million
Eugene Chan U.S. Genomics (Woburn, MA) Technology to rapidly sequence genomes; has raised more than $57 million
Bassil Dahiyat Xencor (Monrovia, CA) Computational protein drug design; human trials of anti-inflammatory drug scheduled for late 2004; has raised $65 million
Benjamin G. Davis Glycoform (Oxford, England) Novel drug delivery systems based on carbohydrate chemistry; has raised $2 million
Christophe Echeverri Cenix BioScience (Dresden, Germany) Drug discovery using RNA interference technology; has raised 11 million euros working
with corporate and academic partners to identify genetic targets for new drugs
Michael E. Gertner Nanomedical Technologies
(San Francisco, CA)
Drug delivery systems using nanometer-sized pores in metallic films that can release medicine in devices such as artery-supporting stents over longer periods than standard polymer coatings
Jay Groves
Synamem (formerly Proteomic Systems) (Burlingame, CA) Drug discovery using “MembraneChip” technology
Andre Koltermann Direvo Biotech (Cologne, Germany) “Directed evolution” to make novel proteins and enzymes for more effective drugs, detergents, and food products; has raised more than $25 million
Anthony Lowman Gelifex (Philadelphia, PA) Hydrogel implants to relieve pain and restore motion in cases of degenerative back disc disease
Gavin MacBeath Merrimack Pharmaceuticals
(Cambridge, MA)
Drug discovery using systems biology approaches to understand complex pathways;
drug for myasthenia gravis in human trials; has raised $25 million in investments
Christophe Schilling Genomatica (San Diego, CA) Computational models of cells that enable biologists to engineer organisms to produce valuable chemicals; $3 million in venture funding
Mijail Serruya Cyberkinetics (Foxborough, MA) Brain-computer interfaces to allow paralyzed patients to communicate or control robotic aids, and to treat epilepsy and depression; has raised $9.3 million
Micah Siegel Concept2Company (Palo Alto, CA) Support for university researchers who wish to start commercial ventures in medical devices, life sciences, and information technology without leaving their current jobs
Jennifer West Nanospectra Biosciences (Houston, TX)
Hollow gold nanoparticles coated with proteins for targeted cancer therapy
Daphne Zohar PureTech Ventures (Boston, MA) Venture creation; helps found and fund life sciences companies

TR100 Biotech and Medicine Honorees

Ameer, Guillermo
Andersson, Helene
Bhatia, Sangeeta
Borisy, Alexis
Chan, Eugene
Dahiyat, Bassil
Davis, Benjamin G.
Echeverri, Christophe
Gertner, Michael E.
Groves, Jay
Hanes, Justin
Koltermann, Andre
Lavik, Erin
Liu, Xiangjun
Lowman, Anthony
MacBeath, Gavin
Ramanujam, Nimmi
Roy, Shuvo
Samudrala, Ram
Schilling, Christophe
Schnitzer, Mark
Serruya, Mijail
Siegel, Micah
Traverso, Giovanni
Vanbever, Rita
Weiss, Ron
West, Jennifer
Zohar, Daphne

What is the TR100?

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