Researchers Seek Basics Of Nano Scale

They're here. Gene chips, carbon nanotubes, and other products, that is, that show that the science of the very small is getting very big. And in biological and biomedical research, nanotechnology--the manipulation and construction of materials and structures at sizes of billionths of a meter--is becoming increasingly important, shrinking the borders between biophysics, biochemistry, structural biology, and other life science fields while seeding new industries. Central to this are exploi

Aug 21, 2000
Dave Amber

They're here. Gene chips, carbon nanotubes, and other products, that is, that show that the science of the very small is getting very big. And in biological and biomedical research, nanotechnology--the manipulation and construction of materials and structures at sizes of billionths of a meter--is becoming increasingly important, shrinking the borders between biophysics, biochemistry, structural biology, and other life science fields while seeding new industries.

Central to this are exploitation of varied genome projects and manipulation of DNA into an easily controlled assembly tool for construction at the nano level, as a scaffolding for macromolecules. DNA arrays have opened scientific communities to new technologies. Along with new cellular probes, molecular motors, and complex systems capable of self-assembly, these technologies promise an exciting path for bioengineers.

There are roadblocks, however. Nanotechnologies cost a lot of money, and it isn't clear how to effectively build an educational and funding framework. With government investment expected to increase, life scientists are seeking a more organized, systematic approach for the field. They say basic tools and the knowledge to use them are essential.

The question of how to develop such a research infrastructure took center stage at a June 25-26 conference, "Nanoscience and Nanotechnology: Shaping Biomedical Research," held in Bethesda, Md. The National Institutes of Health Bioengineering Consortium, or BECON, sponsored the meeting that conference cochair Lynn Jelinski called a "watershed for the development of biomedical nanotechnology." Scientists from a grab bag of disciplines outlined current nanotechnology research and developed some recommendations for NIH's future involvement. Many of the more than 600 participants left voicing specific needs, such as more rigorous interdisciplinary basic research--especially in toolmaking--and further understanding of single molecule and cell biology. Many also considered ways to stimulate interdisciplinary communication and develop a flexible funding structure at NIH and other agencies. They said the agencies' peer review systems must evolve to incorporate crossovers from biology to materials science and engineering.

Symposium participants identified some vital research targets, such as detection and analysis of single molecules and single cells and development of smarter materials for delivery systems and structures. Although single molecule detection has evolved over the last 10 years in physics and chemistry, it has not been fully applied in biology, said Viola Vogel, director of the Center of Nanotechnology at the University of Washington. She indicated that single cell detection is even more nascent. "If you want to make a single molecule measurement in a cell system, you need to develop a lot of the technology that does not exist today," remarked Jay Trautman, CEO of Praelux Inc., Lawrenceville, N.J. That technology should allow researchers to target individual molecules within the cell, track where they are going, and record changes--all without significantly interfering with cellular physiology.

Conference participants also brainstormed about research goals in areas such as developing biomimetic nanostructures, understanding the interface between electronics and biology, and applying nano devices for early detection of disease. Some, such as nanotechnology for drug development, have advanced farther than others. "There's a clear recognition that nanotechnology has already had an impact in diagnostics," declared Chad Mirkin, acting director of Northwestern University's Nano Center. "It's starting to have an impact in therapy, primarily in areas of drug discovery, production, and delivery."

Other fields are still taking baby steps. Ann Mayes, an associate professor in the department of materials science and engineering at the Massachusetts Institute of Technology, said that "we need to achieve a better understanding of molecular and cellular biology and how to manipulate and control cell response. We need more tools."

Resources

Nanoscience and Nanotechnology:
Shaping Biomedical Research symposium Web site
www.masimax.com/becon/index.html

National Institutes of Health BECON grants
grants.nih.gov/grants/becon/becon.htm

The National Nanotechnology Initiative
www.nano.gov

National Nanofabrication Users Network
www.nnun.org

University of Washington Center for Nanotechnology
www.nano.washington.edu

Stanford University BIO-X Program
cmgm.stanford.edu/biochem/biox

Northwestern University Nano Center
www.chem.northwestern.edu/NanoWeb/index.html

The nanoManipulator system at the University of North Carolina, an NIH National Research Resource
www.cs.unc.edu/Research/nano/doc/biovisit.html

Tools of the Scale

Conference participants agreed about the need for tools. "Developing tools of scale and developing ways to deal with the enormous amount of information that comes with addressing processes of scale provide us with, very quickly, new ways to describe what is a biologic state," said Richard D. Klausner, director of the National Cancer Institute. "We would like the ability to detect these processes earlier at the molecular level."

Many participants also agreed that to develop tools and better standards of measurement for making nano-size structures, there should be a cultural transition in grant agencies' peer review to reflect the interdisciplinary nature of fields such as biomedical nanotechnology. "Emergent fields are unrecognizable by study sections," said George Whitesides, professor of chemistry at Harvard University. Richard Zare, Stanford chemistry professor and symposium cochair, said that the current NIH infrastructure does not effectively support the kinds of research now needed, as review sections are organized to mirror the department-based structure of universities. "If NIH continues to do business as it does business, it runs the risk of losing a major opportunity to advance our understanding of life processes and our treatment of disease states," he said. This means moving away from traditional hypothesis-based peer review so that more exploratory tool-design research can get off the ground.

Another major need identified was that for greater collaboration and communication between existing disciplines. "A lot of investigators in biosciences in the past had difficulty obtaining NIH funding, in part because NIH required a different style, but also because ... more communication [was necessary] between developers and biologists," Vogel explained. To make that dialogue happen, participants suggested more conferences and workshops to bring together researchers from all corners of the scientific community.

NIH, however, maintains that its 3-year-old BECON committee is beginning to alleviate some of the problems identified at the symposium. "The whole point of BECON is to find a way to functionally cut across the sort of stovepiping that goes on in the university and that goes on here," said Wendy Baldwin, NIH deputy director for extramural research and chair of BECON. She said the consortium also has explicitly made the language of its grant application review criteria less hypothesis driven. However, she added that this kind of social change takes time. "Peer review is risk averse. Every funding agency struggles with conservatism." Nevertheless, NIH is eager to build a biomedical nanotechnology program that emphasizes the field's evolution over the last three years, said NIH's acting director Ruth Kirschstein, who cited an almost doubling of NIH support for biomedical engineering since 1997. This is part of the federal government's growing nanotechnology support that culminated in January with the FY2001 budget's National Nanotechnology Initiative (NNI), which also approximately doubled federal nanotechnology investment. If the initiative is approved by Congress this fall, NIH will receive $36 million--a 13 percent increase from NIH's 2000 nanotechnology funding--for long-term fundamental research at the university level, creation of research centers, and study of the social and ethical impact of nanotechnology research.

Developing Educational Initiatives

BECON, composed of representatives from NIH's 25 institutes and other federal agencies, including the National Science Foundation and the U.S. Department of Energy, is the base for NIH nanotechnology efforts. "We're looking at how we can build on that next generation of researchers," explained Baldwin. "It's not a simple task to figure out how you bring many different, complex fields to bear." In addition to meetings such as this one, the consortium encourages grant applications geared toward training and bioengineering research partnerships. Training scientists is fundamental to the growth of the field, participants said. Jelinski, who is vice chancellor for research and graduate studies at Louisiana State University, talked about a new "T-shaped" person with disciplinary depth, in biology for example, but with the ability, or arms, to reach out to other disciplines. "We need to encourage this new breed of scientist," she said.

New programs aim to realize this kind of T-shaped scientist. Stanford University has created an interdisciplinary program it calls BIO-X and is part of a five-university consortium--the National Nanofabrication Users Network, which includes Cornell University; Pennsylvania State University; University of California, Santa Barbara; and Howard University--that provides resources for nano-scale modeling and construction. Most recently, at the end of July, the University of Washington announced what it called the nation's first doctoral degree program in nanotechnology at its Center for Nanotechnology. Funded with a $2.7 million grant from NSF, the program's students will obtain doctorates in a primary area of study--biochemistry, biophysics, or another science and engineering discipline--while pursuing nanotechnology research through the 3-year-old center.

Some may ask if robotics will make humans unnecessary, a so-called transhuman condition. Steven M. Block, a Stanford University biology professor, cautions about the hype surrounding all things nano and advises a more sober focus on the real research now possible, especially in the life sciences. Yet investment in tool development and education and community development are high on the wish lists of researchers who hope to partake in the next advances nanotechnology promises for biology, medicine, and especially genetics. "We can't reap the benefits of decoding the human genome unless we invest this way," said Zare. S

 

Dave Amber (damber@nasw.org) is a freelance science writer in College Station, Texas.