THE NATIONAL ACADEMIES KECK FUTURES INITIATIVE DESIGNING NANOSTRUCTURES AT THE INTERFACE BETWEEN BIOMEDICAL AND PHYSICAL SYSTEMS

CONFERENCE FOCUS GROUP SUMMARIES

Pre-Conference

Keck Center of the National Academies

Washington, D.C.

and

Arnold and Mabel Beckman Center of the National Academies

Irvine, California

September 18-19, 2004

Conference

Arnold and Mabel Beckman Center of the National Academies

Irvine, California

November 18-21, 2004

THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu



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The National Academies Keck Futures Initiative Designing Nanostructures at the Interface Between Biomedical and Physical Systems: Conference Focus Group Summaries THE NATIONAL ACADEMIES KECK FUTURES INITIATIVE DESIGNING NANOSTRUCTURES AT THE INTERFACE BETWEEN BIOMEDICAL AND PHYSICAL SYSTEMS CONFERENCE FOCUS GROUP SUMMARIES Pre-Conference Keck Center of the National Academies Washington, D.C. and Arnold and Mabel Beckman Center of the National Academies Irvine, California September 18-19, 2004 Conference Arnold and Mabel Beckman Center of the National Academies Irvine, California November 18-21, 2004 THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu

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The National Academies Keck Futures Initiative Designing Nanostructures at the Interface Between Biomedical and Physical Systems: Conference Focus Group Summaries THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 NOTICE: The focus group summaries in this publication are based on focus group discussions during the National Academies Keck Futures Initiative Designing Nanostructures at the Interface between Biomedical and Physical Systems Conference held at the Arnold and Mabel Beckman Center of the National Academies in Irvine, CA, November 18-21, 2004. The discussions in these groups were summarized by the authors and reviewed by the members of each focus group. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the focus groups and do not necessarily reflect the view of the organizations or agencies that provided support for this project. Funding for the activity that led to this publication was provided by the W.M. Keck Foundation. Based in Los Angeles, the W.M. Keck Foundation was established in 1954 by the late W.M. Keck, founder of the Superior Oil Company. The Foundation’s grant making is focused primarily on pioneering efforts in the areas of medical research, science, and engineering. The Foundation also maintains a Southern California Grant Program that provides support in the areas of civic and community services with a special emphasis on children. For more information, visit www.wmkeck.org. International Standard Book Number 0-309-09668-5 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu. Copyright 2005 by the National Academy of Sciences. All rights reserved. Cover: Image courtesy of Samuel Stupp, Northwestern University. Adapted by the New York Academy of Sciences.

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The National Academies Keck Futures Initiative Designing Nanostructures at the Interface Between Biomedical and Physical Systems: Conference Focus Group Summaries THE NATIONAL ACADEMIES Adviser to Nation on Science, Engineering, and Medicine The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www.national-academies.org

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The National Academies Keck Futures Initiative Designing Nanostructures at the Interface Between Biomedical and Physical Systems: Conference Focus Group Summaries THE NATIONAL ACADEMIES KECK FUTURES INITIATIVE NANOSCIENCE AND NANOTECHNOLOGY STEERING COMMITTEE CHERRY MURRAY* (Chair), Deputy Director for Science and Technology, Lawrence Livermore National Laboratory JACQUELINE BARTON (NAS), Arthur and Marian Hanisch Memorial Professor of Chemistry, Division of Chemistry and ChemicalEngineering, California Institute of Technology WAY KUO** (NAE), University Distinguished Professor and Dean of Engineering, University of Tennessee, Knoxville ROBERT LANGER** (NAS/NAE/IOM), Kenneth J. Germeshausen Professor of Chemical and Biomedical Engineering, Massachusetts Institute of Technology ALBERT PISANO (NAE), FANUC Chair of Mechanical Systems, Electronics Research Laboratory, University of California, Berkeley ERKKI RUOSLAHTI (NAS/IOM), Distinguished Professor, The Burnham Institute ROGER TSIEN (NAS/IOM), Investigator, Howard Hughes Medical Institute, Professor, Pharmacology and Chemistry and Biochemistry, University of California, San Diego *   Also Chair, Planning Committee **   Also Member, Planning Committee

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The National Academies Keck Futures Initiative Designing Nanostructures at the Interface Between Biomedical and Physical Systems: Conference Focus Group Summaries THE NATIONAL ACADEMIES KECK FUTURES INITIATIVE NANOSCIENCE AND NANOTECHNOLOGY PLANNING COMMITTEE ANGELA BELCHER, John Chipman Career Development Associate Professor of Materials Science, Massachusetts Institute of Technology SANGEETA BHATIA, Associate Professor of Bioengineering and Medicine, University of California, San Diego SHANA KELLEY, Assistant Professor of Chemistry, Boston College YUE KUO, Dow Professor of Chemical Engineering, Electrical Engineering and Materials Science & Engineering, Texas A&M University GREG LANZA, Assistant Professor of Medicine, Adjunct Assistant Professor of Biomedical Engineering, Washington University Medical Center CATO T. LAURENCIN (IOM), University Professor, Lillian T. Pratt Distinguished Professor and Chair, Department of Orthopedic Surgery, Professor of Biomedical and Chemical Engineering, University of Virginia Health System DAVID A. LAVAN, Assistant Professor of Mechanical Engineering, Yale University HARI MANOHARAN, Professor, Department of Physics, Stanford University ANDY MCCAMMON, J. E. Mayer Professor of Theoretical Chemistry, University of California, San Diego CHAD A. MIRKIN, George B. Rathmann Professor, Department of Chemistry, Director, Institute for Nanotechnology, Northwestern University MILAN MRKSICH, Professor of Organic Chemistry, University of Chicago GEORGE WHITESIDES (NAS/NAE), Mallinckrodt Professor of Chemistry, Harvard University ERIK WINFREE, Assistant Professor, Departments of Computer Sciences and Computation & Neural Systems, California Institute of Technology Staff KENNETH R. FULTON, Executive Director MARTY PERREAULT, Program Director MEGAN ATKINSON, Senior Program Specialist GINGER CLARK, Senior Program Specialist ALEX COHEN, Senior Program Specialist

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The National Academies Keck Futures Initiative Designing Nanostructures at the Interface Between Biomedical and Physical Systems: Conference Focus Group Summaries The National Academies Keck Futures Initiative The National Academies Keck Futures Initiative was launched in 2003 to stimulate new modes of scientific inquiry and break down the conceptual and institutional barriers to interdisciplinary research. The National Academies and the W.M. Keck Foundation believe that considerable scientific progress will be achieved by providing a counterbalance to the tendency to isolate research within academic fields. The Futures Initiative is designed to enable scientists from different disciplines to focus on new questions, upon which they can base entirely new research, and to encourage and reward outstanding communication between scientists as well as between the scientific enterprise and the public. The Futures Initiative includes three main components: Futures Conferences The Futures Conferences bring together some of the nation’s best and brightest researchers from academic, industrial, and government laboratories to explore and discover interdisciplinary connections in important areas of cutting-edge research. Each year, some 100 outstanding researchers are invited to discuss ideas related to a single cross-disciplinary theme. Participants gain not only a wider perspective but also, in many instances, new insights and techniques that might be applied in their own work. Addi-

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The National Academies Keck Futures Initiative Designing Nanostructures at the Interface Between Biomedical and Physical Systems: Conference Focus Group Summaries tional pre- or post-conferences build on each theme to foster further communication of ideas. Selection of each year’s theme is based on assessments of where the intersection of science, engineering, and medical research has the greatest potential to spark discovery. The first conference explored Signals, Decisions, and Meaning in Biology, Chemistry, Physics, and Engineering. The 2004 conference focused on Nanoscience and Nanotechnology: The Merger of Cell Biology and Physical Machines, A 21st Century Revolution. Theme of the 2005 conference is The Genomic Revolution: Implications for Science and Health. Futures Grants The Futures Grants provide seed funding to Futures Conference participants, on a competitive basis, to enable them to pursue important new ideas and connections stimulated by the conferences. These grants fill a critical missing link between bold new ideas and major federal funding programs, which do not currently offer seed grants in new areas that are considered risky or exotic. These grants enable researchers to start developing a line of inquiry by supporting the recruitment of students and postdoctoral fellows, the purchase of equipment, and the acquisition of preliminary data—which in turn can position the researchers to compete for larger awards from other public and private sources. National Academies Communication Awards The Communication Awards are designed to recognize, promote, and encourage effective communication of science, engineering, and medicine within and beyond the scientific community. Each year the Futures Initiative honors and rewards individuals with three $20,000 prizes, presented to individuals who have advanced the public’s understanding and appreciation of science, engineering, and medicine. Awards are given in three categories: book author; newspaper, magazine, or online journalist; and TV/radio correspondent or producer. The winners are honored during the Futures Conference. In addition, during the first 18 months of the Keck Futures Initiative, the Academies undertook a study on facilitating interdisciplinary research. The study examined the current scope of interdisciplinary efforts and provided recommendations as to how such research can be facilitated

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The National Academies Keck Futures Initiative Designing Nanostructures at the Interface Between Biomedical and Physical Systems: Conference Focus Group Summaries by funding organizations and academic institutions. Facilitating Interdisciplinary Research (2004) is available from the National Academies Press (www.nap.edu). About the National Academies The National Academies comprise the National Academy of Sciences, the National Academy of Engineering, the Institute of Medicine, and the National Research Council, which perform an unparalleled public service by bringing together experts in all areas of science and technology, who serve as volunteers to address critical national issues and offer unbiased advice to the federal government and the public. For more information, visit www.national-academies.org. About the W.M. Keck Foundation Based in Los Angeles, the W.M. Keck Foundation was established in 1954 by the late W.M. Keck, founder of the Superior Oil Company. The Foundation’s grant making is focused primarily on pioneering efforts in the areas of medical research, science, and engineering. The Foundation also maintains a Southern California Grant Program that provides support in the areas of civic and community services with a special emphasis on children. For more information, visit www.wmkeck.org. The National Academies Keck Futures Initiative 5251 California Avenue – Suite 230 Irvine, CA 92617 949-387-2464 (Phone) 949-387-0500 (Fax) www.nationalacademies.org/keck

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The National Academies Keck Futures Initiative Designing Nanostructures at the Interface Between Biomedical and Physical Systems: Conference Focus Group Summaries Preface At the National Academies Keck Futures Initiative Designing Nanostructures at the Interface between Biomedical and Physical Systems conference, participants were divided into interdisciplinary focus groups. The groups spent eight hours over two days exploring diverse challenges at the interface between physical science, biomedical science, engineering, and technology. The focus groups were not expected to solve the particular problems posed to the group, but rather to come up with a consensus method of attack and a thoughtful list of what we know and don’t know how to do, and what’s needed to get there. The composition of the groups was intentionally diverse, to encourage the generation of new approaches by combining a range of different types of contributions. The groups included researchers from science, engineering, and medicine, as well as representatives from private and public funding agencies, universities, businesses, journals, and the science media. Researchers represented a wide range of experience—from postdoc to well-established in their careers—from a variety of disciplines that included chemistry, biology, physics, engineering, bioinformatics, medicine, toxicology, and applied anthropology. The conference committee identified five objectives for the focus groups:

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The National Academies Keck Futures Initiative Designing Nanostructures at the Interface Between Biomedical and Physical Systems: Conference Focus Group Summaries To approach nanoscience/technology and biomedicine from the perspective of specific problems having potentially revolutionary impact, rather than from the perspective of extensions of existing technology To allow a group of people with a broad range of backgrounds to pool their insights and creativity to work on a shared problem To identify ideas and insights, common to a number of working groups, and to identify important fundamental problems in nanoscience/ technology with the potential for very large impact on biomedicine To identify the best (by whatever metrics seem to fit) big problems in biology and biomedicine, to which nanoscience/technology might be applied, and to identify gaps in knowledge that limit progress in the solution of these problems To allow individuals to make connections with one another in small working groups The groups needed to address the challenge of communicating and working together from a diversity of expertise and perspectives, as they attempted to solve a complicated, interdisciplinary problem in a relatively short time. Each group decided on its own structure and approach to tackle the problem. Some groups decided to refine or redefine their problems, based on their experience. Each group presented two brief reports to the whole conference: (1) an interim report on Saturday to debrief on how things are going, along with any special requests (such as an expert in DNA sequencing to talk with the group); and (2) a final briefing on Sunday where each group: Provided a concise statement of the problem Outlined a structure for its solution Identified the most important gaps in science and technology and recommended research areas needed to attack the problem Indicated the benefits to society if the problem could be solved Based on the group interaction and the final briefings, graduate science writing students in each group wrote the following summaries, which were reviewed by the group members. These summaries describe the problem, approach taken, group dynamics, the process the group followed to achieve its results, and benefits to society of the problem solution.

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The National Academies Keck Futures Initiative Designing Nanostructures at the Interface Between Biomedical and Physical Systems: Conference Focus Group Summaries Contents     Conference Summary   1      FOCUS GROUP SUMMARIES         A Micro System to Isolate, Sequence, and Identify DNA from a Small, Low-Concentration Sample   7     Build a Synthetic Self-Replicator 15 Build a System That Will Detect Disease In Vivo and Report Back Results   23     Build a Cell-Chip Interface to Sense Response to Drug Leads and Toxins   31     Sequence a Single Molecule of Protein   39     Build a Glucose Sensor to Circulate (Implant) In Vivo in Humans and Regulate Insulin   45     An In Vivo Nanofactory: The Medicine of the Future   53

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The National Academies Keck Futures Initiative Designing Nanostructures at the Interface Between Biomedical and Physical Systems: Conference Focus Group Summaries     Improve Hydrogen Production by Genetic Methods: Design a Better Nanomachine   61     Design Principles of Living Systems   67     Grow a Biological In Vitro Power Source on a Chip   73     APPENDIX          Pre-Conference Program   81      Conference Program   85      Participants   91