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Building better drugs
New tools are often the driving force behind advances in life sciences, and Massachusetts has the tool-making legacy to turn that into a competitive advantage for local companies
By Robert Gavin, Globe Staff | April 11, 2005

Life sciences are blazing new frontiers, and pushing them forward are innovators who think outside the box -- toolbox that is.

While often overlooked, tool makers represent a vital component of the state's life sciences cluster, and their long history here gives Massachusetts a competitive advantage that few other states can match. Their ever-improving gizmos, from powerful microscopes to precise sensors, enable scientists to see what was once unseen; measure what was once immeasurable; and test what couldn't be tested.

As a result, drug companies, biotechnology companies, and university laboratories are making advances in basic research, drug discovery, and the treatment of disease. At MIT, for example, the development of a tool to analyze the body's complex sugars is leading to a safer and more effective form of heparin, a blood-thinning agent used to prevent strokes.

The pharmaceutical giant Pfizer Inc., which has its research center in Cambridge, is able to screen up to 100,000 compounds a day as it seeks new drugs, thanks to a system, developed by Caliper Life Sciences Inc. of Hopkinton, which essentially shrinks a laboratory onto a chip.

FEI Co., an Oregon firm with a major facility in Peabody, recently unveiled a scanning electron microscope that allows researchers to analyze particles, and thus determine which shapes are most effective for drug delivery within the body. Seahorse Bioscience of Billerica will soon bring to market a device that measures the respiration of cells.

''Periods of great discovery in science are almost always preceded by the development of new tools," Boston University Professor Matthew A. Nugent once wrote in the Proceedings of the National Academy of Sciences.

Massachusetts has a long tradition of tool making, which, over the course of two centuries, has underpinned the state's innovation economy. Industrial historians trace the roots to the earliest days of the republic, when the federal armory in Springfield pioneered a manufacturing system using interchangeable parts.

Instead of employing craftsmen who each built muskets from stock to barrel, the Springfield Armory made parts separately for later assembly. This method required pieces to be manufactured to precise specifications so they'd fit and work together, and, consequently, demanded mechanical tools to reproduce such precision time after time.

Ultimately, the tool-making skills developed in Springfield were adapted, advanced and diffused to support a host of industries, from textiles to telecommunications, shoes to semiconductors, watches to wireless, said Michael Best, professor emeritus at the University of Massachusetts at Lowell. ''The technology domain is all the time changing," Best said, ''but this tooling industry gives us a regional competitive advantage."

Today, tool and instrument makers like Caliper, FEI, and Seahorse are critical components of the state's innovation infrastructure. Also, like universities, they are helping attract cutting-edge companies to the state, said Zvi Rozen, deputy director of Massachusetts Technology Collaborative's John Adams Innovation Institute.

Massachusetts's rich cluster of tool makers was a key reason that Pfizer established its Research and Technology Center in Cambridge, said Philip Vickers, who leads the center. For example, said Vickers, Pfizer's scientists are able to meet frequently with their counterparts at Caliper, and collaborate on modifications to make the screening tool more effective.

''It's an enormous business advantage," Vickers said. ''If we couldn't have that relationship with Caliper and other companies, we wouldn't be located in Cambridge."

Caliper's screening tool combines several technologies, including robotics and microfluidics, the science of handling liquids in amounts that are invisible to the eye. Caliper's system transfers thousands of different compounds onto a chip with channels narrower than a human hair, and tests them against biological targets, such as proteins.

A single operator can run 100,000 tests in a day, not only identifying compounds that might make effective drugs, but also possible side effects. ''You can save yourself a lot of time and money," said Kevin Hrusovsky, Caliper's chief executive.

Seahorse offers a different technology, which allows scientists to test new drug candidates without killing the target cells, as other methods do. Seahorse's method, which monitors cells' oxygen consumption, keeps them alive.

So, for example, a compound designed to speed up cell metabolism as a potential treatment for obesity might be tested by looking for an increase in oxygen consumption. Since their technology doesn't harm the cells being tested, company officials added, scientists can observe the effects of drugs over a period of time.

FEI's increasingly powerful microscopes, meanwhile, allow scientist to see how cells and their components behave. Increasingly, said Steven Berger, FEI's chief operating officer, scientists are learning that the shape of biological building blocks, such as proteins, are critical to understanding how they function, making it vital for researchers to actually see them.

At MIT, Ram Sasisekharan, a professor of biological engineering, is taking on a more complex substance: sugars. His tool combines analytical technologies, such as mass spectrometry, enzymes that act as biological scissors to slice and dice the sugars, and information technology to sequence the sugars, a method to decode and describe their chemical composition.

In addition to the breakthroughs on heparin, the blood thinning agent, Sasisekharan's tool has discovered that sugars surrounding cancer cells might play a role in triggering tumor growth. Consequently, adjusting the composition of the sugars with drugs might block tumors.

As tools like these help spark life science advances, they are also advancing Massachusetts competitiveness, said Pat Larkin, director of John Adams Innovation Institute.

''These technologies are tremendous enablers, and these type of firms are really economic anchors," he said. ''They are key sectors of the innovation economy."