Medical Device Daily Washington Editor

WASHINGTON — The first day of this week's two-day conference on nanotechnology hosted by the National Academy of Sciences (Washington) included discussions of technological advances as well as the public perceptions faced by those who would do business in nanotechnology.

While the range of topics was wide, the regulatory aspects that will confront nanotechnology received little attention, despite the FDA conference on just such concerns this past October (Medical Device Daily, October 12, 2006) and the agency's recent guidance on in vitro diagnostic multivariate assays (Medical Device Daily, Feb. 12, 2007).

Jeffrey Schloss, PhD, program director for technology development coordination at the National Human Genome Research Institute (NHGRI), gave an overview of recent efforts in gene sequencing and the nanotechnologies that have aided that effort.

NHGRI, a division of the National Institutes of Health, has mapped the genome, but "clearly, we don't know nearly everything we need to know" about using genomic information, he said.

Schloss said that one of the ways NHGRI has attempted to economize on this expensive investment has been to sequence the genomes of other life forms because "by looking across evolution, we get a lot of information about the human genome." He also cited the continued high cost of mapping genes.

"The cost of sequencing had come down quite a lot . . . but it has still has taken us 10 years to get two orders of magnitude reduction in cost," he said, adding that in the early years of the effort the mapping equipment consisted of "lots of big machines handling lots of sequences," so that sequencing labs looked "like a factory."

In 2005, NHGRI reported that it will focus on getting the cost of mapping a mammalian genome down to $100,000, with a longer-term aim of reducing this cost to $1,000.

The development of appropriate nanotechnologies is "an important goal" in getting to that cost, Schloss said.

He said that Richard Mathies, a professor of chemistry at the University of California at Berkeley in 1994, led a team that built a high-speed microfabricated capillary array electrophoresis instrument that drove down sequencing times, doing the job in "in a much smaller volume [of space] in a much faster time." That innovation employed chemically etched glass and photolithography to electrically excite and steer DNA into separate channels, or capillaries, for further analysis. Though at the time, the technique was quite advanced, it required three months for mapping a genome with the use of a single machine.

In the mid-1990s, 454 Life Sciences (Brandford, Connecticut) developed a system that capturee and cloned genomic fragments for analysis with "a relatively simple machine, a detector and a camera," Schloss said, employing a reaction known as pyrosequencing, which types genetic material by picking up the release of pyrophosphate and allowing a lab to read 800 bases of DNA at a time vs. the 200 for then-existing technology.

454's equipment was desktop sized, much smaller than the factory-sized equipment that was current. (Last month, 454's parent company, Curagen (New Haven, Connecticut) agreed to sell 454 to Roche (Basel, Switzerland) for about $150 million) (Medical Device Daily, March 30).

"The next step is sequencing by synthesis," or SBS, Schloss said, and "to do this on an array" that will process hundreds of thousands of molecules at a time instead of dozens or hundreds.

Solexa (Hayward, California), recently bought out by former rival Illumina (San Diego), has made a clonal single-molecule arrays that uses SBS, and generating up to "a billion bases of usable data per run," which the firm's site says is 100 times the speed of conventional methods.

Other companies cited by Schloss in this particular race include Pacific Biosciences (Menlo Park, California), working on a method to visualize enzyme activity on DNA in real time; and Visigen Biotechnologies, working on massively parallel arrays that, according to the company's web site, use "DNA polymerases and nucleoside triphosphates to function as direct molecular sensors of DNA base identity." The site states that its arrays "will allow us to achieve a sequencing rate of 1Mb/sec/machine."

Vikki Colvin, PhD, professor of chemistry and chemical engineering at Rice University (Houston), discussed nanotechnology sustainability, pointing out that it doesn't take much for a novel approach to medicine, food or anything else to go "from wow to yuck — it can happen." She said this could just as easily happen in nanotechnology.

One of her cases in point was dichloro-diphenyl-trichloroethane (DDT), used to tamp down mosquito populations to reduce the incidence of malaria, "but we don't use that chemical because of the environmental consequences," despite uneven evidence of its harm to humans.

Colvin warned the backers of nanotechnology that "you often cannot anticipate the consequences" of a new technology, but failure to look into the possibility can "basically shut down the technology completely."

Colvin reminded the audience that the "yuck factor" for nanotechnology includes the novel "Prey," by Michael Crichton, a 2002 entry on the New York Times list of bestsellers. "Prey" tells the story of an experiment that results in the inadvertent release of a cloud of nanoparticles functioning as intelligent micro-robots with a predatory bent.

However, "another type of yuck factor are the controls" with which technology is applied, and in foreign nations, these often violate the local sense of social justice., Colvin said. "There's a very strong mistrust of U.S. technology," largely invisible to those living in the U.S., Colvin remarked.

Dealing with misperceptions of a new technology is "a challenge, a risk communication challenge," Colvin said.

She said that many in industry are inclined to think that the bad news is the only news that gets into print, but he pointed to studies of media coverage showing that "80% of the stories are positive."

However, one-sided representations of new technologies can "create polarization between groups where none existed," she commented, adding that "its not surprising that we see these simplistic" treatments of profoundly complicated subjects.

For the public, "the jury is still out," she said

And she emphasized that to avoid the potholes that have claimed other promising technologies, attention to communication is vital.

"Risk communication, finding ways to convey information to the public and policymakers, is critical" to the continued viability.