Science & Technology

What Biotech Needs From Technology

Polling a panel of experts reveals a range of wish lists as broad as the field itself

by Jeffrey M. Perkel

Innovation, at least in biotechnology, stands at the intersection of technology and science. Where would biotech be without the polymerase chain reaction, liquid-handling robots and automated DNA sequencers? For that matter, where would biotech be without advanced imaging systems, detection reagents and bioinformatics? From microtiter plates to microarrays, technology development has changed the way biotechnology is done, raising the bar on scientific progress and forcing researchers to reassess their limitations.

To get a sense of just what is possible, I surveyed thought leaders in academia and biotech, asking them how innovation has shaped their present, and will continue to mold their future. The mix of experts polled here includes pioneers of DNA sequencing and microfluidics, the cell biologist behind the Brainbow "glowing brain" mouse, an imaging-platform developer, a molecular diagnostician and a systems biologist. As you will see, the technologies that these experts find important—and their visions of the future—are as varied as their respective fields.

Today’s Technology Helpers

To get a feel for the mix of existing technologies that make a difference, consider these replies. Harvard University geneticist George Church, for example, says that advances in computing power, oligonucleotide microarrays, microfluidics and next-generation DNA sequencing technologies all propel his research. Brainbow developer and neurobiologist Jeff Lichtman, also of Harvard, credits advances in optical and electron microscopy. He says, "We are using both to probe the three-dimensional structure of the nervous system at higher resolution than previously possible."

By contrast, systems biologist Trey Ideker of the University of California at San Diego, tips his hat to technologies for high-throughput protein–protein interaction mapping and genotyping. The "grand opportunity for the next decade of research," Ideker says, is "to understand the complex relationships connecting the vast number of uncharacterized single-nucleotide polymorphisms to human pathology." Without such a map of these single-base variations in DNA, he says, making sense of the data would be "like trying to decipher how your computer works without the wiring diagram."

In short, new technologies push biotechnology forward. Genotyping and interaction mapping help researchers identify novel therapeutic targets, for instance, and microfluidics-driven miniaturization and automation make once-intractable processes robust.

“ The grand opportunity for the next decade of research is to understand the complex relationships connecting the vast number of uncharacterized single-nucleotide polymorphisms to human pathology. ”

Tomorrow’s Technology Desires

Technology, though, isn't static, and there's still much that researchers cannot do. For example, Church says that he would like to have the ability to do "automated homologous allele replacement at nearly 100 percent efficiency without selection." That, plus easily created patient-specific induced pluripotent stem cells would enable researchers to "change the genome to be exactly what you want for gene therapy or for testing hypotheses," he says. Suppose, for instance, a researcher finds several potentially causative alleles for some phenotype in a cell line; by making those changes one at a time or in combination in mammalian cells, it becomes possible to pin down the critical variants. "You can go from association to causation," he says.

Lichtman says his research would benefit from "tools that monitor the function—activity—of the nervous system at millisecond time scales and micrometer length scales." He explains: "Ultimately the structure of [the] nervous system needs to be linked to the function, so [having] functional assays that match the resolution of the structural probes would be highly useful. I assume new ways of looking at things may ultimately provide assays for poorly understood diseases, such as of the nervous system."

Also hoping to "see" more, James Mansfield, director of multispectral imaging systems at Cambridge Research & Instrumentation, says that his firm could use access to new and simpler multiplex histological and fluorescent labeling methods—not to mention more and better-annotated clinical histology samples. "These will greatly enhance the ability to interrogate tumors for a wide range of cell-signaling pathways," he explains, thus accelerating personalized medicine.

At Genomic Health, which is a molecular diagnostics firm, chief scientific officer Joffre Baker says that internal research and development efforts would benefit from integrating ever-greater numbers of sequenced human genomes into a functional genomics database that links sequence to biology and to disease. Such a database "will immeasurably accelerate the discovery of optimal new drug targets and diagnostic biomarkers," he says.

Ideker's wish list also includes more and cheaper sequencing, as well as "more, better, faster and cheaper tools for measuring different types of protein interactions," both in model organisms and in humans, as well as more of the complete network maps that such tools will yield. "Imagine computer models of these pathways being available in the clinic," he says. "Enter the nurse, who collects a patient's genotype through DNA sequencing, along with various clinical phenotypes and symptoms. These data get projected onto the pathway model, resulting in a detailed diagnosis of the illness and a personalized treatment plan."

Funding The Future

Beyond wanting new tools and techniques, some scientists also want to change the system. For instance, Harvard microfluidics expert George Whitesides hopes for—among other things—"a system for support of fundamental research that was not captured by advocacy groups and risk-averse peer review and distributed funds in a way that was more to the benefit of ultimate users." That might be some of the most wishful thinking of all.

We do know, however, that technology advances will rewrite what researchers can and cannot accomplish, continuing the cycle of innovation and discovery that drives both academic and industrial progress. Funding agencies, therefore, must adjust to recognize technology development as a worthy research goal in its own right, says Lichtman. "Technology, in my view, drives progress in scientific research, not the other way round, so we need to invest in efforts to improve tool building in scientific research."

Yet, not everyone sees technology development as a make-or-break for biotech. "That isn't what is holding us back right now," says Gajus Worthington, president and chief executive officer of Fluidigm. "Instead, it is the efficient application of current technologies and on areas that will turn out to have an impact."

In the end, advances in biotech will surely depend on wise use of today's tools, and clever development of tomorrow's new ones.