U.S. GOVERNMENT PRINTING OFFICE

WASHINGTON : 

For sale by the Superintendent of Documents, U.S. Government Printing Office

Internet: bookstore.gpo.gov Phone: toll free (866) 512–1800; DC area (202) 512–1800

Fax: (202) 512–2250 Mail: Stop SSOP, Washington, DC 20402–0001

89–610 PDF 2004

S. HRG. 108–247

ROUNDTABLE ON HEALTH TECHNOLOGY

HEARING

OF THE

COMMITTEE ON HEALTH, EDUCATION,

LABOR, AND PENSIONS

UNITED STATES SENATE

ONE HUNDRED EIGHTH CONGRESS

FIRST SESSION

ON

EXAMINING HEALTH TECHNOLOGY, FOCUSING ON NANOTECHNOLOGY,

INCLUDING THE DANGERS AND SOCIETAL IMPLICATIONS, MARKET

BARRIERS AND CHALLENGES OF INTERDISCIPLINARY RESEARCH, AND

THE FEDERAL ROLE OF FUNDING, COORDINATION, AND PRIORITY

SETTING

SEPTEMBER 23, 2003

Printed for the use of the Committee on Health, Education, Labor, and Pensions

(
COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS

JUDD GREGG, New Hampshire, Chairman

BILL FRIST, Tennessee

MICHAEL B. ENZI, Wyoming

LAMAR ALEXANDER, Tennessee

CHRISTOPHER S. BOND, Missouri

MIKE DEWINE, Ohio

PAT ROBERTS, Kansas

JEFF SESSIONS, Alabama

JOHN ENSIGN, Nevada

LINDSEY O. GRAHAM, South Carolina

JOHN W. WARNER, Virginia

EDWARD M. KENNEDY, Massachusetts

CHRISTOPHER J. DODD, Connecticut

TOM HARKIN, Iowa

BARBARA A. MIKULSKI, Maryland

JAMES M. JEFFORDS (I), Vermont

JEFF BINGAMAN, New Mexico

PATTY MURRAY, Washington

JACK REED, Rhode Island

JOHN EDWARDS, North Carolina

HILLARY RODHAM CLINTON, New York

SHARON R. SODERSTROM, Staff Director

J. MICHAEL MYERS, Minority Staff Director and Chief Counsel

(II)
CONTENTS

STATEMENTS

TUESDAY, SEPTEMBER 23, 2003

Page

Gregg, Hon. Judd, a U.S. Senator from the State of New Hampshire ................ 1

Schloss, Jeffrey A., M.D., National Human Genome Research Institute, Washington, DC; Patricia M. Dehmer, Ph.D., Director, Office of Basic Energy

Sciences, Department of Energy, Washington, DC; Samuel I. Stupp, Ph.D.,

Director, Institute For Bioengineering and Nanoscience in Medicine, Northwestern University, Chicago, IL; and Todd Lizotte, Vice President, Research

and Development, Nanovia, LP, Londonderry, NH ........................................... 2

ADDITIONAL MATERIAL

Statements, articles, publications, letters, etc.:

Mr. Todd Lizotte (graphics) ............................................................................. 25

Ms. Patricia M. Dehmer (graphics) ................................................................. 41

(III)

(1)

ROUNDTABLE ON HEALTH TECHNOLOGY

TUESDAY, SEPTEMBER 23, 2003

U.S. SENATE, COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS, Washington, DC.

The committee met, pursuant to notice, at 10 a.m., in room SD– 430, Dirksen Senate Office Building, Senator Gregg, (chairman of

the committee), presiding.

Present: Senators Gregg and Murray.

OPENING STATEMENT OF SENATOR GREGG

The CHAIRMAN. Let me begin the hearing. It is ten o’clock. I expect we will have members wandering in and wandering out. There

is a lot going on, plus I guess the traffic is a disaster this morning,

which is too bad, but typical, I guess.

Let me first say on this subject, technology, that this committee

is extremely interested in this issue because of its implications specifically to health care, obviously, which are dramatic. The fact that

if we look to the future, this appears to be the science and the area

where we are going to see an acceleration of more than geometric

proportions, nano proportions, that will dramatically affect everything we do, I suspect, but especially affect our health care as we

deliver it in this country and the world.

As I look at the American experience as we move into this century and we see that so much of our manufacturing in a free market economy is moving overseas, our capacity as a nation to compete is going to be tied to our capacity to lead technologies which

lead the world, and nanotechnology is clearly one of those areas

where we, as a Nation, need to lead and are leading and the government has an obligation to be a sister in this effort.

And so I wanted to hold this hearing today, first to get a thumbnail sketch as to what is happening in the area, but second, to hear

ideas as to what we should be doing, if anything, beyond what the

government is already doing, and interestingly enough, we appear

to be involved in this fairly aggressively already, which is hopefully

good news. And third, issues that we see coming down the road

which we need to address as a matter of public policy—ethics

issues, things which we need to address early so that they don’t become bumps or impediments to the expansion of the technology and

the use of the technology in a variety of different ways.

The CHAIRMAN. I very much appreciate the fact that the witnesses are here today and we have such an expert group. Dr.

Schloss is the National Human Genome Project researcher in this

area and, of course, NIH is making a major effort in this area. The
2

NSTC, which is the National Science and Technology Council,

which coordinates the activities in this area, is the representative

from NIH on that.

Dr. Dehmer is with the Basic Energy Sciences Office at Oak

Ridge, and this is an area where we have a huge interest in

nanotechnology research and appreciate her taking the time to be

here.

Dr. Stupp is the Director of the Institute for Bioengineering and

Nanoscience in Medicine at Northwestern, which is on the cutting

edge of the use of this area of technology in an interdisciplinary

way.

And Todd Lizotte is from New Hampshire and has actually commercialized some activities in this area that are exciting, especially

in the use of very small penetrating micro lasers that allow for the

introduction of extremely small holes and various applications.

I appreciate your all taking the time to come here. Why don’t we

just begin. I want to do this sort of in a discussion format, and so

I would suggest that each of you sort of give us what your thoughts

are in five or 10 minutes and then we will move on to discussion,

hopefully between you folks and me and whoever else comes by, as

to where we are going.

Dr. Schloss?

STATEMENTS OF JEFFREY A. SCHLOSS, M.D., NATIONAL

HUMAN GENOME RESEARCH INSTITUTE, WASHINGTON, DC.;

PATRICIA M. DEHMER, PH.D., DIRECTOR, OFFICE OF BASIC

ENERGY SCIENCES, DEPARTMENT OF ENERGY, WASHINGTON, DC.; SAMUEL I. STUPP, PH.D., DIRECTOR, INSTITUTE

FOR BIOENGINEERING AND NANOSCIENCE IN MEDICINE,

NORTHWESTERN UNIVERSITY, CHICAGO, ILLINOIS; AND

TODD LIZOTTE, VICE PRESIDENT, RESEARCH AND DEVELOPMENT, NANOVIA, LP, LONDONDERRY, NEW HAMPSHIRE

Dr. SCHLOSS. Thank you, Senator Gregg, for the opportunity to

come this morning. I have probably got way too many slides, and

I understand that. I have a lot of examples at the end. We will go

through a number of them, and then when we have seen enough

examples, we will stop.

We have probably all heard the definition—I have put it in here

just to make sure that people understood what we are talking

about. Research and development at the atomic molecular or

macromolecular levels, so we are being fairly inclusive there. The

scale is important. It is one-to-100 nanometers, and we really focused on this idea of a fundamental understanding of phenomena

and materials and this idea of creating and using structures, devices, and systems with novel properties because of the size scale.

So all of those things have to come together to comprise this new

field of nanoscience and nanotechnology.

So from the biology or health perspective, I am thinking of—a

number of us are thinking of this in at least two ways that are not

totally mutually exclusive—they overlap a lot—one of which is the

idea that nanotechnology is operating at the same size scale as biological processes. So this offers us really a unique vantage point

from which to interact with the biology of life. One of the key
3

issues there is we can really work and study biology at the single

molecule level.

The other aspect of this is that nanotechnology has grown up in

other fields generally, in the physical sciences, and these fields

have generated a number of incredibly important materials, devices, and tools that we can apply with the appropriate research to

biological systems. And so we can fundamentally understand biological systems and use that information to translate out into utility for biology and medicine and for other areas of technology, and

then we can also bring into biology the discoveries from other

fields.

So we coordinate nanotechnology research at NIH through the

Bioengineering Consortium, or BEACON, and we need to do something like that, because with 27 institutes and centers, we need a

central way to deal with this, and this just represents the various

components of the NIH that are involved in this process.

You will notice actually that we have three other agencies that

are represented in the lower right-hand corner who participate in

BEACON activities, and this is one of the ways that we can coordinate across agencies.

One of the important activities of BEACON has been to hold a

series of symposia where we reach out to various communities that

have, in many cases, not been the typical NIH communities and

use this as an opportunity for people to meet each other, to understand the vision of other scientific fields as related to biology and

medicine and also to understand how we can do business at NIH

differently in order to promote research in those areas. And as you

see, one of these was in nanoscience and nanotechnology back in

June of 2000.

So the support for nanotechnology at NIH occurs through a number of different kinds of programs. A few of them actually say

nanotechnology in the program announcement, but most of them

actually don’t. Because the mission of the NIH is, of course, diagnosis and treatment of diseases, they tend to be framed in that context, but there are many opportunities to apply nanotechnology

ideas in those contexts.

So this is just a list of program announcements that have been

generated through BEACON, through this trans-NIH efforts, and

the first two are specifically for nanoscience and nanotechnology.

The first is for sort of standard research grants that NIH would

provide to research institutions, colleges, universities, and the second is through the SBIR program to help these kinds of ideas and

tools get out through commercialization. The others are more general programs that BEACON has developed, again, through the

auspices of all the institutes of the NIH, under which people can

apply for nanotechnology and nanoscience research support.

And then this is just the list of a few of the many program announcements from institutes, usually from consortia of institutes,

under which nanotechnology can be supported, and I have broken

them down just for the examples here into sort of the different

areas of basic research or sensors or tissue engineering, disease

and syndrome research, and diagnostics and therapeutics to give

some idea of the breadth of areas where we believe nanotechnology

is going to be important in the context of NIH.
4

So our investment in nanotechnology has well more than doubled

in the time that the NIH budget has doubled. These are fairly conservative projections, I think, for the out years. Of course, 2003

isn’t finished yet, so we will only tally that at the end of 2003. And

we have actually new programs. The first program announcement

I showed you is actually a new one where we received many applications, and I think our portfolio is likely to grow faster than this.

Through the National Nanotechnology Initiative, several grand

challenges have been enunciated and the one for health care is

clearly the one that is most relevant to NIH. And the areas where

we think that our activities—where nanotechnology is going to be

important are listed here, detecting disease very, very early, before

there is any substantial deterioration of health, in the tissue regeneration area, and in therapeutics delivery.

So the rest of the slides are really examples. Obviously, there is

a lot of information covered in each slide, and I won’t go through

it. I will try to point out some key issues.

So most of these slides represent projects that NIH is currently

supporting. In a couple of cases, there was no good website or place

where I could get nice illustrations, so I have illustrated it with

other research that is not being supported by NIH, but in each

case, it represents research that we are supporting in other grants.

And the other thing I have done here is not only indicate the

grantee, but also the Institute of the NIH that is supporting it so

that you will have some sense of the way that this crosses the NIH.

So this represents a material called quantum dots that allow us

to do things that we have been able to do in the past with organic

dyes, but probably a lot better than we were able to do it in terms

of the different colors which we can use to indicate different cellular entities and also the kinds of signals we can detect in our imaging.

And so in this case, it is showing that we can use these quantum

dots to label various proteins inside of cells and learn about them.

These can also be used for imaging in whole animals, and this is

just a study sort of to show you where we are. The key thing here

is this—in this case, the quantum dots are coated with a material

that didn’t work very well, and I am just going to run this movie

that runs over 60 minutes. All you are supposed to see here is that

the signal except in the liver disappears very fast. When you coat

it with a different material, the quantum dots stay in the blood circulation for 190 minutes.

So this is where we are. We are trying to learn how to use these

materials to do in vivo imaging, in this case of a mouse—a mouse

or a rat, sorry, I can’t remember which—in order to be able to, in

this case, visualize circulation, but this will be used potentially for

labeling many other things in in vivo imaging.

This is another study also using in vivo imaging using quantum

dots, again, a collaboration by the company that has commercialized these and Cornell University, in which they are doing

much finer resolution of the circulation, of the circulatory system.

And I wanted to point out this additional item that was noted

in this publication. No adverse effects on the mice were observed

and the mice are being maintained to investigate long-term Q-dot

toxicity. This is a very important point, clearly. We have to under-
5

stand how these nano scale materials interact with the body. We

are now developing the tools, as you can see here, to be able to actually do that.

So there are a number of other sensor examples here in the

slides. This is an example, instead of coating the outside of the

nano material with materials that will allow for specific biological

visualization here, it is the construction of the nano material itself

that is going to produce fluorescent signals that can be visualized

in the light microscope and that will indicate various interesting

and important things about the cells’ physiology.

Here is a use of carbon nanotubes that have very unique electrical properties. These tubes are one nanometer in diameter. They

can be centimeters long. The idea here is to put something at the

tip of the nanotube that will allow us to detect some specific biological molecule and then perhaps use these in catheters to detect

things inside the body.

Another thing that this slide points out is partnerships between

agencies. So in this case, it is a collaboration between the National

Cancer Institute and NASA.

The next few slides, I won’t talk about in detail. They are other

kinds of sensors technologies that are being supported, in this case,

under SBIR grants, the work coming from Harvard. Here is another one, work actually supported at Massachusetts General Hospital, and this is a technology that might be used not only to do

diagnostics in test tubes, but also potentially in vivo imaging once

again.

Quantum dots have many other uses in, for example, in high

throughput screening. There are many other ways to do high

throughput screening. There are some very, very novel ways to use

nanotechnologies. In this case, it is for measuring DNA, information from DNA using a pore that is exactly the same size in diameter as a DNA molecule. This would be a very new approach to DNA

sequencing. It uses new physics, new fabrication technologies, and

there are partnerships all over the country that are working on

this.

There are a number of aspects of tissue engineering, most of

which I won’t cover because Dr. Stupp is going to cover that, but

there are two different approaches here. One is modifying existing

approaches to tissue engineering and the other is create completely

new ones.

There are examples in drug delivery, either for creating new

ways to deliver existing drugs to make them more effective, or creating completely new drugs that didn’t exist before, that work by

different principles using nanotechnologies.

This is the last slide I will show. This is a multifunctional device

based on some very elegant chemistry—beautiful molecules, actually—and the idea here is you will create a complex by this very

tightly, carefully controlled chemistry where you could bring the

complex to a very specific place in the cell, use this for biopsies or

in vivo imaging in the whole person to find out where this material

is localized to target a specific thing that has gone wrong, such as

cancer cells, and use the same device to deliver therapeutics.
6

So I will stop there because I have run just a little bit long. I

have additional slides that we can use later on to illustrate various

points if that seems appropriation.

And so now I will close down my presentation and we will move

to the next one.

The CHAIRMAN. Thank you, Doctor.

Dr. Dehmer?

Ms. DEHMER. Senator Gregg, Senator Murray, it is really a pleasure to be able to represent the Department of Energy here this

morning. I am Pat Dehmer. I head the Office of Basic Energy

Sciences in the Office of Science in the Department of Energy.

I have given a lot of talks on nanoscience to folks who don’t have

a lot of physical science training and I find that starting with a

poster that I made several years ago is the best way to tell people

what some of the challenges are.

This is the scale of things poster, and I am actually going to

use—each one of these tics represents an increase of a factor of ten,

so this might be ten, 100, 1,000, and so forth. This is a scale of increasing size.

The nano world, as Jeff said, is about one-to-100 nanometers.

The micro world, which we are much more familiar with, is about

one-to-100 micrometers. These two scales differ by a factor of 1,000.

Quite remarkably, until very recently, we were not able to see

anything in the nano world. We could only see things in the micro

world. And I think it is not an understatement to say that our ability to see atoms has driven both the nanotech and the biotech revolutions, and this came about relatively recently, in the last 30 or

40 years or so.

So let us just look at some of the things that nature makes in

these various size ranges and some of the things that man makes

in these various size ranges.

In the micro world, the world that we are familiar with, we have

red and white blood cells, we have phylage, we have human hair,

and if you want to get bigger, we have pesky things like dust mites

and ants and mosquitoes sucking the red out of the things natural

slogan. So this, we are very familiar with. We have been able to

see these using visible light microscopes.

At the nano scale, things are more complicated. Here, we see

atoms of silicon, solid silicon, spaced by a few tenths of a

nanometer. Here, we see deoxyribonucleic acid, DNA, this wonderful polymer that transmits all the information of life. It is actually

about 2.5 nanometers wide. If you go to a slightly larger biological

molecule, a rotor, it is about ten nanometers wide. It is at the

nanometer scale that Mother Nature starts assembling things, and

it is at that scale that things start having their properties. Metals

start having metallic properties, biological molecules start having

the properties of living things. It is an extremely important world.

It took Mother Nature about three billion years to perfect these

molecules. By contrast, man has been working at control over materials for a couple of thousand years if you ignore rock hand axes,

which are about a million years old.

So what has man done? On the right hand side of the chart, in

the micrometer scale region, you see these beautiful MEMS devices, micro-electro mechanical devices. A little tooth of one of these
7

gears is about the same size as a red blood cell. We have been able

to drive downward in our industrial fabrication to the micron level,

and one of our speakers here this morning, Mr. Lizotte, is going to

tell us about some of the things that they have done in this size

region.

However, if you go much lower than this, you can no longer do

things with fabrication. You have to use a different way, a different

approach. If you go way down to the level where Mother Nature

starts putting things together, the atomic level, in a tour de force,

we have been able—researchers have been able to move atoms literally one at a time into quantum structures, circles—this is a circle of atoms—or they have been able to make slogans. Everyone

has seen the IBM slogan written with atoms. This is a tour de force

and it is not likely to go into mass production if you physically

have to move an atom one at a time.

The way that we are going to have to solve the problem of making nano structures is to do what Mother Nature did, to learn how

to self-assemble nano structures to get what we want, and here is

a self-assembled structure that another one of our speakers, Dr.

Stupp, has made, and he will tell you more about that.

It is only through self-assembly that we are going to be able to

make nano structures to do what we want to do, and the big challenge in the decades to come is to take different kinds of nano

structures that nature hasn’t thought about, put them together in

various ways so that we can make things that nature hasn’t done,

and in particular, make things that are more robust than natural

systems. Natural systems are remarkable, but they don’t withstand

high temperatures, high pressures, and other kinds of corrosive

atmospheres.

So this, then, is the scale of things and it presents some of the

challenges. One of the things that Jeff talked about is coupling

things that man makes with things that nature has made, to make

nano structures that live inside the body that can detect disease,

that can act as sensors, and so forth.

So this, in a nutshell, is the scale of things and where we are

in man’s attempt to control materials at this scale.

So what is the role of the Department of Energy in all of this?

The Department has several roles, and I alluded to one a moment

ago when I said that it has only been recently that we have actually been able to see things at this size scale. If you look at the little tiny spectrum right in the middle of the chart, that is the visible light region, and things that are larger than that, you can see

with a visible light microscope. For example, you can see red blood

cells with a visible light microscope. Things that are smaller than

that, you can’t see. The laws of physics simply forbid you from looking smaller.

So in order to see things at the nano scale, we have to come up

with probes that are themselves the size of atoms, and there are

three kinds of probes that have emerged, X-rays, neutrons, and

electrons. The Department of Energy recognized quite a few years

ago that these would be extremely important probes of matter.

By the way, the discovery of each one of those—electrons, neutrons, and X-rays—was made about the turn of the last century
8

and they were so important that each one of them garnered for its

discoverer the Nobel Prize.

These probes are so important that they have become the basis

for major user facilities that are shown here. These are the user

facilities for X-ray scattering and neutron scattering that are operated by the Office of Basic Energy Sciences and the Department of

Energy. We operate four huge light sources around the country. We

have three operating neutron facilities, one at Argonne, one at Oak

Ridge, and one at Los Alamos. This is the spallation neutron

source, a $1.4 billion construction project that is underway at Oak

Ridge National Laboratory, and on the drawing board we have a

fourth generation X-ray source.

Together, these plus the electron beam scattering centers that we

also run, have really revolutionized our ability to see things. And

again, it is not an understatement to say that the ability to see

how Mother Nature puts things together has driven both the

nanotech and the biotech revolutions, and this is one of the main

contributions of the Department of Energy’s Office of Science.

When the National Nanotechnology Initiative came along, we

recognized the importance of these major facilities at the nano

scale and part of the Office of Science’s contribution to the NNI

was to make user facilities for nanoscience that are sited alongside

of these major facilities for seeing atoms, and these are shown

here. Under construction right now, we have five user facilities for

research at the nano scale at Brookhaven National Laboratory next

to the National Synchrotron Light Source at Argonne National

Laboratory. This is being funded joint by the State of Illinois and

DOE, and it is appended to the advanced photon source, a major

synchrotron.

We have one at Lawrence Berkeley National Laboratory, again,

which is adjacent to the advanced light source. We have a center

going up at Oak Ridge National Laboratory, which is attended to

the spallation neutron source, and we have a center at Los Alamos

and Sandia National Lab which is appended to the Lujan Neutron

Scattering Center, plus also their facility for MEMS, which is extremely important.

So this is part of the contribution of the Department of Energy.

Another part of the contribution is the support of fundamental research, and about 60 percent of the fundamental research in

nanoscience that has been competed recently has gone to the university community.

This is an example in biomolecular materials, which I am not

going to go over in the consideration of time.

This is one that is very interesting and it demonstrates a principle that sometimes you don’t know what you are going to get out

of fundamental research. This was a project at Argonne National

Laboratory—where I spent my formative years, but not on this

project—on ultrananocrystalline diamond, UNCD. And if you don’t

think of the University of North Carolina when you say that acronym, you are better than I am. This is ultrananocrystalline diamond, and what it shows is that the diamond film forms in grains

that are at the nanometer size. This is about three to five

nanometers across.
9

This diamond film has some extraordinary properties. It is as

hard as natural diamond. It has low coefficient of friction. And

these two properties mainly can be used as coatings that are hard

and wear-resistant. It has very high electro-conductivity that can

be varied by many orders of magnitude, and that means it is great

for MEMS devices because it can be little electrical conductors. It

has high field emission from micropoints—here are some micropoints—and that means it can be used as a signaling device because electrons can come off of it. It is chemically inert and it is

bioinert and it is biocompatible, and those things are very important.

And here is one of the artificial retina projects that is ongoing

now in the United States, and this film is at the back of the retina

to help bring the image from the outside into the nerve cells in the

eye.

So the folks who thought about making this diamond film never

had a clue that it might be used some day in an artificial retina,

and this is some of the magic of nanoscience.

So with that, I am going to thank you for your attention and I

am going to turn it over to Sam.

The CHAIRMAN. Thank you, Doctor.

[The prepared information of Ms. Dehmer may be found in additional material.]

The CHAIRMAN. Dr. Stupp?

Mr. STUPP. Good morning. Thank you, Senator Gregg, Senator

Murray, for the opportunity to brief you this morning on my views

on nanotechnology and the future of medicine, which is what I was

asked to do.

There is no need to define nanoscience, nanotechnology anymore.

Dr. Schloss and Dr. Dehmer have done a great job of that. But I

simply want to remind everybody that cells function through interactions among nanostructures. In fact, these are highly

orchestrated——

The CHAIRMAN. Excuse me. I have got to take a call. I will be

right back.

Mr. STUPP. Cells function and make life possible by highly orchestrated interactions among nanostructures. Most of those

nanostructures are actually proteins. So with the capabilities that

we have now to create nanostructures with basically any chemistry

that is available in the planet, almost, then we are in a position

to make artificial ones that can talk directly to the cells and then

control cell behavior or probe cells.

Now, one of the interesting opportunities in this field is regeneration of body parts, regenerative medicine. Targeted drug delivery is another one, and, for example, the area of more humane

chemotherapy or more effective chemotherapy could fall under this

category. We could also use the nanostructures, the artificial ones,

to, in fact, detect disease at very early stages.

The related opportunities, of course, that come with all this

knowledge base have to do with biosecurity, for example, and certainly genome mapping, which is also very important in regenerative medicine, as well.
10

So let me focus on regenerative medicine, which I have used as

an example, to illustrate how nanotechnology is embedded in this

problem.

So, so far, this is what we do, what is illustrated here on the

right-hand side. We stick metals and ceramics, huge chunks of

metal, in fact, and ceramic and other materials, composite materials, to fix joints and to fix blood vessels with artificial polymers,

for example. What we should be looking to into the future is essentially the left-hand side, that is, have a scheme that allows us to

regenerate all tissues of the body in adulthood. This is the target.

Now, why is regenerative medicine important? Well, it is important certainly because humans are living longer now and they will

probably continue to live even longer. And the current generation,

of course, is very interested in high quality of life. Humans want

to be, at least in developed countries, there is a lot of desire to be

physically active and have a higher quality of life into a more advanced age. This is very much characteristic of generations now. So

regenerative medicine, therefore, will have a great human impact.

But, of course, there are other issues, you know. For example,

the societal implication here is to basically think about the fact

that we then need to keep populations in a highly productive and

ideal State into a more advanced stage, and that brings, of course,

all kinds of problems.

The needs for regenerative medicine are many, but I wanted to

focus on a few here which I think are important. Real progress in

this field, which is highly interdisciplinary, will require combining

the frontiers of technology, in this case nanotechnology, with biology and clinical medicine. This is all about interdisciplinary science

and technology, and countries that do not know how to tackle with

interdisciplinary science and technology will not win in this field,

both from a human point of view, of course, and an economic point

of view, because this is also an economic opportunity.

We have in this country many entrepreneurial bright students

which are going to be attracted to this objective because this is one

of the great biomedical challenges of the century, to be able to regenerate the human body. But they need to be backed up by an

interdisciplinary culture which is not there yet. So this is an issue

that we need to ask questions about all the time because no one

has the right formula yet for interdisciplinary education and research. The universities need to deal with this constantly. The

agencies, of course, have to deal with it, as well, and they have a

very critical role to play.

The issue is that teams of scientists and engineers of different

fields is not enough. What you really need is multilingual scientists

and engineers that can effectively do interdisciplinary work.

Now, here are some of the great targets, in my view, of regenerative medicine. We certainly should have as a developed society, we

should have a way to reverse paralysis, and we don’t have a way

to reverse paralysis now, reverse blindness. So what needs to be

done here is spinal cord regeneration and retinal regeneration, for

example. Heart regeneration is extremely important, as well, and

this is something that afflicts a large section of the population. If

we could do that after heart attacks, then quality of life would be

much higher. The same thing with stroke, which is a problem for
11

almost a million people every year just in the U.S. There is need

for cell therapies, basically to substitute for the pancreas that

doesn’t produce insulin, and here, regenerative approaches are also

important, as well.

Everybody would like to have access to cartilage and adulthood,

because that causes the damaged cartilage, which no one in this

room can grow cartilage right now because I suspect there is no

one here that is under 18. So it is all gone. If we have an injury

in cartilage, it will cause a lot of pain, decrease quality of life, and

this attempts to fix this problem. It is also a multibillion dollar

business. So if we had solutions, it would be a very attractive problem.

No one knows how to repair bone universally, and, of course,

bone repair is something that afflicts an extremely large portion of

the population every year. And, of course, nobody dies with their

original permanent teeth, which is another reality here. It would

be great if we could regenerate enamel, for example, and not have

to use dentures and all the porcelain and metal that gets placed

in our mouths throughout life.

So how is nanotechnology embedded in this problem of regenerative medicine? Well, the key is that we need to have scaffolds. To

regenerate tissues in adulthood is like building a building. You

need a scaffold. So the scaffold is needed, which is made up of

nanostructures that can talk directly to cells and instruct them on

what to do next. Of course, a lot of the information to design the

scaffolds, to design the nanostructures of the scaffold, need to come

from genomic and proteinomic information so that we know which

signals we are to provide to cells in order to regenerate different

tissues.

We also need to be concerned with stem cell biology. We are

going to have to know how we want to deal with that problem.

And, of course, regulatory work, such as the FDA, will need to be

important, as well.

So I want to illustrate the problem with this nanostructure

which was developed in my laboratory. We basically, using the

spirit of nanoscience and nanotechnology, went out to create an artificial nanostructure that would mimic collagen fibrils, because collagen fibrils are everywhere in your body. They are the most common component of the natural scaffold where cells live in the various tissues of the body. So having a way to create an artificial one

where we can change, let us say, the chemistry here to customize

it to neurons or to retina or to heart or to bone, is extremely important.

We were able to do that in the slide which you already saw in

Dr. Schloss’s and Dr. Dehmer’s talks. It shows a molecular rendition of this nanostructure. Just to show you how interdisciplinary

this activity is, this structure, which should be of great interest to

the NIH community because it is for regenerative medicine, the

fundamental science that was needed to develop it actually came

from support from the Department of Energy. And so this shows

you how difficult it is to predict where things are going to come

from and why is it so important to constantly be interested in

interdisciplinary science and research.
12

These nanostructures combine proteins, for example. So if we

know from genomics and proteinomics what proteins make what

tissues grow, we can stick them there by design using specific techniques. We can load the middle of the structure in that cargo compartment with drugs, like hydrophobic drugs, for example, that are

important in creating strategies for regenerative medicine, to actually make them work in the clinic.

This slide shows you how those fibers really look like when they

are in three dimensions, and that is a picture of the scaffold where

the cells can be. And so they form networks and the networks have

some strands which are single nanofibers, other strands which are

groups of twos or threes.

We have been able to customize them for the spinal cord injury

recently, a problem, and so we have already in the laboratory

nanofibers which cause neuroprogenitor cells to differentiate specifically into neurons and very rapidly. So this slide is an illustration of that differentiation. The green says that they are neurons,

and you see very, very extensive neurites coming out of a cluster

of progenitor cells.

The most interesting aspect of this problem is that other cells

like glial cells have not appeared in the presence of our scaffold.

Glial cells are implicated in the spinal cord injury problem because

glial cells, when there is a spinal cord injury, they create a scar

which prevents neurons from reconnecting and then healing.

So these synthetic nanostructures were able to direct progenitor

cells to go only into the direction of being neurons and nothing else,

and normally, in materials that had been explored for this purpose,

you get mixtures of cells. You get glial and neurons. And so this

will be important for spinal cord injury repair.

Bone, which is very important for the entire population because

we will always depend on a healthy skeleton. We can’t move

around with a fractured skeleton. We have problems, osteoporosis,

for example, and all of these things that connect very much to high

quality of life.

The same nanofiber, the same synthetic structure, we were able

to customize it so that it would grow bone crystals very rapidly

that mimic exactly those found in natural bone. We were able to

reconstruct the crystallography and the nanostructure details of

bone mineral present in natural bone using a different molecular

structure in the nanofiber. So it is possible to customize this to different tissues.

In the case of cartilage, which is this yellow region shown here,

and if you have a cartilage injury, you will be miserable for a long

time and maybe the rest of your life because it is very difficult to

regenerate it, we have found nanostructures in which chrondocytes,

which are the cells of cartilage, can actually produce—remain in

the phenotype that is characteristic of chrondocytes and produce

the proteoglycons which are so critical to formation of cartilage.

This area right here indicated as PA gel is chrondocytes sitting

on nanostructures. Over here, these are chrondocytes sitting on tissue culture plastic or some other material that is not designed, and

so there, the cells lose the characteristic phenotype which allows

them to produce cartilage. So it is a very exciting possibility that

we actually can go in, design a nanostructure, and talk directly to
13

cells and get them—send them in pathways that will lead to regenerated tissues.

Another great target is the heart, and I think here the same

thing will apply. We will need to find out what are the right signals, the right epitopes, as biologists call them, and growth factors

that are necessary for this to happen.

Now, to conclude, I just want to give you a few thoughts about

how I think we should proceed. It is clear that these artificial systems in regenerative medicine, which is the example I chose to use,

they will be developed by highly creative teams of physical scientists, engineers, biologists, and clinicians, everybody working together. But all the members of the team will have to speak several

languages. Otherwise, this will never happen.

So the interdisciplinary culture is not necessarily going to

emerge spontaneously. There are people that are naturally interdisciplinary. Others are not naturally interdisciplinary, and Federal agencies, for example, can do a lot to promote that culture

through the programs they create. I think NIH and DOE both are

doing an excellent job so far, but I don’t want to say that it is a

perfect job yet because there is a lot of work to be done, and frankly, the formula is not there yet.

I think universities are willing to do technology transfer. That is

another issue that is important here. We must be very much aware

of the fact that large companies are really not doing the R&D work

that is going to be necessary for this field. And the venture capitalists, which are terribly scared right now for whatever happened in

the 1990s, are pulling back and they are not ready to invest in

high-risk quantum leap projects. And so again, the Federal agencies need to intervene and help move these processes along.

I would say that we need to ask the question of whether or not

our country is offering the best possible resources we can offer to

make science an attractive career for young people. I question that.

I am not really sure. We can discuss that later if you would like.

But I think having those resources is critical for a segment of the

population.

There is a segment of the population that goes into science that

will be scientists no matter what you do, okay, so you don’t need

to do anything for those. But there is another segment that are undecided and they make selections about business careers, legal careers, medical careers, different careers, and going that pathway

for accidental reasons sometimes or just because the right opportunities are not presented to them at the right time. So that is where

we have to look, because I don’t think we have just the large—we

do not have the right number of people, of bright young people in

this country going into science and engineering careers right now.

Business as usual will not do. I mean, to go after this particular

objective that I have described to you. Thank you.

The CHAIRMAN. Thank you, Doctor.

Mr. Lizotte?

Mr. LIZOTTE. Good morning, Senator Gregg and Senator Murray.

I appreciate this opportunity to come here. I am definitely very intrigued by a lot of the work that is happening.

I dealt in the area of practical, bring-it-to-the-market kind of

areas and my discussion will be from a small business perspective,
14

some of the areas that we do in micro as we are transitioning and

looking toward a future for nanotechnology.

One of the things, I will just introduce our company in general,

what we see as transitioning from micro to nano, some of our products in homeland security and defense, and some of our traditional

markets over the years, and I will end it with some closing statements.

NanoVia, I am the Vice President of R&D at NanoVia, and typically where we operate is we operate from the point of looking out

into the universities and in the national labs and looking for opportunities, and that is when materials are created, when processes

are created, even if in the basic scheme of things. A lot of the technology we deal with here is for micromachining or microengineering, microfabrication is technology that came out of the microelectronics industry. What we are doing is adapting it to applications

which can be commercially viable.

Now, those commercial applications can be things as simple as

computers. One of the areas that we focus on is the efficient attachment of chips, computer chips and processors to chip carrier devices. Also, in the area of microfluidic delivery, including catheter

delivery, schemes for delivering drugs or therapeutic drugs, and

also our latest technology stuff in pulmonary drug delivery.

Our services, once again, are geared toward the research, process, and equipment development within our marketplace, which is

micro systems, or microelectromechanical systems and passive mechanical micro devices.

Some of the images you can see which we always throw up for

scale purposes, the upper image there is a human hair with small

sections cut out of it using our particular laser technology, and

where you can see that, we can create very high finesse cuts

through different materials without damaging the surrounding

structure.

One of the things I like to do with talking to people about scale,

especially when you are talking microtechnology and

nanotechnology, is to say that in the micro scale, one micron is

equivalent—if you look at a human hair is about 100 to 150 microns, whereas a nanometer is one-80,000th of the diameter of a

human hair. So it is a very broad scale.

Now, as far as commercial development in nanotechnology from

a small business perspective or getting it out into the commercial

area, it is going to be a long coming. There is not going to be anything super-substantial in the new few years, other than maybe in

the bio areas. But we do see some things, especially in materials,

that we are interested in. We are looking at materials that can

withstand, as was said earlier, different environments and utilizing

that material in our processes.

One of the things that we kind of look at microtechnology is we

say micro is the new macro for the United States. The traditional

manufacturing of welded assemblings and stuff of that nature is

really getting shipped offshore. Even from 1999, when we started

out, we were developing a process to triple the throughput of chip

packages for laptop computers and we really thought we had something. We pushed it forward and built a tool and what we found

was all of the market between 1997 and about 2000 shipped to Tai-
15

wan and China. So with that much manufacturing overseas, we

saw, well, there is probably not too much opportunity for us to

build equipment in that area, so what we end up doing is licensing

that technology, and we ended up licensing that technology to a

Japanese concern.

But we doubled back and we focused on things that we felt were

key areas where we could see a potential for manufacturing in the

United States, and the areas we see, of course, are medical device

and diagnostics, some of the microwave components or communications components and high-value-added products. We still see these

being competitively built in the U.S. and we see a market there for

us in the future.

One of the things that Dr. Stupp had talked about, which we are

also very—we say is very important, is—we call it a multidiscipline

education. One of the things that is interesting about engineers is

that when engineers enter into a workforce, typically, they go into

a company and they might have one discipline, myself as a mechanical engineer. But I entered into an organization which demanded that I know optics and I know lasers.

So what ends up happening is in that kind of an environment

where profitability and you get delivering to the customers there,

you learn those disciplines and you learn them rapidly. And over

a short career of 10 years, you might also dabble in electronics or

electricity for some applications or even semiconductor processes.

So what happens is that in the manufacturing environment, we are

creating engineers and manufacturing engineers who have multiple

disciplines, and also in chemistry and such of that nature.

So we see ourselves as a small business and as a growing business in this market as being the facilitators of taking the technology that is developed in the laboratories and the universities

and actually applying them to potentially commercial products.

Now, a lot of the things that we have been working on in regards

to products, like I will just say from 15 years ago, you know, we

started drilling holes in small devices for ink jet and now we are

drilling—and those holes are anywhere from 100 microns to 75 microns, around the diameter of a human hair, and now we are drilling one-micron holes to facilitate the atomization of pharmaceuticals that can be delivered down into the deep lung.

What we see with the micro to nano is an opportunity for us to

really stake a claim in this new market that is coming out, and

what we see is one of the things that is a big barrier to some of

the foreign competitors, specifically in the Far East. We tend to say

that they operate in a herd mentality, which is typically an engineer or staff engineer within a facility, there will be ten people applied in the manufacturing floor to solve one problem.

I personally have consulted in Taiwan and I have seen this happen, where it takes them a long time to—and that is because they

do not operate the same way we do and they also don’t have a

multidiscipline ethic in regards to when they get into the workforce. They only want to do their one job, and I see that as a benefit in regards to our competitiveness.

As far as this market, we see opportunities in new capital equipment requirements. As has been discussed, we only recently have

been able to see down to an atomic level. That gives us the poten-
16

tial of actually developing the new tools that are coming out and

I think we might have a strategic advantage there. Those tools can

be built by companies like ourselves. Once the basic science has

been done, we can apply it and productize it and bring it into the

market.

One of the other things that is key in all these markets is U.S.

companies hold a significant market share in most of the diagnostic

aspects, in microelectronic ICs and communications devices. So I

see that we have a strong position.

Here are some applications that we are doing in regards to the

homeland security and defense. Off to the side, you can see this one

micron diameter hole. To drill a one-micron hole is pretty easy if

you do one. We do a thousand every second and multiple—we have

a system which does even more than that every quarter of a second

and we do it to a six sigma level, which basically is about one defect per million. That is a requirement, especially for drug delivery,

because you can’t have a situation in which someone tries it and

it fails, especially if you are delivering maybe something therapeutic that they need immediately, say for diabetes or something

like that.

We are working on some other applications in regards to making

microstructures and even nanostructures. In our world, we look at

nanostructures from our perspective at below a micron. So one micron is 1,000 nanometers, you know, a tenth of a micron, in that

range, 100 nanometer range is really what we are calling our nano

at this level at this point. And one of the things we are doing is

structures for different types of ID, holographic ID for anti-counterfeit technology, and also some military applications for tagging

military vehicles to identify them as friend or foe from aircraft and

such, some interesting optical technology.

This is an example which I talk about in regards to pulmonary

drug delivery and where I see that there is a potential here to kind

of revive some of our traditional manufacturers. One of the things

is we have an opportunity in some select areas to work on machine

technology and get a foothold in there, process technology in regard

to how the things are processed, the assembly technology, and in

this case, we are talking about some traditional lamination and application which is done by people like make paper and such. But

if some of these traditional corporations could transfer over into

these newer areas, they could find newer markets and maybe higher value added markets, which could help them out and transition

from old technology.

And then, of course, product technology. That is where the key

is. You can have one element of it, but if you are selling the product, then you are talking about true manufacturing, and then, of

course, down to the end user.

Some of our traditional markets, I already talked about, microelectronics packaging, single-dose commercial pulmonary drug delivery devices, which we look at potentially third-world medical applications for giving a lot of these countries the ability to do immunizations and stuff of that nature without very complex delivery

systems, holographic and defractive optics, and fluid metering,

which includes ink jet, because that is always a good market out

there for us financially, but bio analysis. We do a lot in regard to
17

micro channel plates and some advanced stuff that we call ‘‘lab on

a chip,’’ and maybe even create devices which these people could

use in regards to their work, basically, create devices which allow

them to do their work easier or faster and such.

In closing, one of the things that we have been thinking about

is what is the role of government in regards to small business. The

Small Business Innovative Research grants are very interesting vehicles. Our experience with them, though, is that even if you get

through the first phase, you are not going to get through the second phase. There is a potential you won’t get to that second phase.

And the thing is, is that a lot of the times, you will see a lot of

these programs don’t go past the first phase.

In a small business environment where we are looking at—where

we have technology, we believe in our technology, and if we show

a track record of success with our company, one of the things is we

don’t see the SBIR program as being very attractive, because what

it does is it maybe gives you one piece, but it doesn’t guarantee you

to bring it to the next level of marketing it.

We are trying to see if there is a potential of talking about things

where it is a small business entrepreneurial grant, where we are

talking about something where we do have a product, or we have

something which is maybe out of the laboratory which is fundamentally there but needs to be productized and is maybe a higher level of potential success.

The SBIR first phase grants are about the same level of risk.

Our feeling is if there is a potential link, commercial entity, to one

of these programs where it is just at the cusp of being productized,

that would probably allow us to bring it into the mainstream and

apply it. It is one thing that we are thinking of looking at.

And we look at these grants, looking at funding different levels

of where these products come out.

Another area is a multiindustry alliance grant, and this would be

something we have been contemplated and which we currently do

without Federal funding, and that is we look for traditional manufacturers who maybe are, say, a molding company, and they are

very good at what they do and they have very highly skilled or a

highly-skilled workforce, but we need micro molding. And what we

do is we introduce to them the micro molding concept, which gives

them an entry into this market they have never even been exposed

to. If there was a way in which we could look at some type of funding to bring certain products out this way, where we maybe link

these different traditional manufacturers, maybe in different regions of the country and different disciplines and try to bring it together to maybe bring them into this new type of technology.

One of the things that, I think just as a final note, is that unless

you have a workforce that can handle this type of technology, even

if you develop it, you just can’t bring it to market from a product

level. One of the things that we have now is even with some of the

students and stuff that are coming into the workforce is they just

don’t have the background in microtechnology, and now we are

talking about nanotechnology. There is definitely a shortfall, as Dr.

Stupp was talking about, in regards to their education and their

ability to adapt into a micro world when they were educated at a

macro level. That is definitely something.
18

We typically see about a three-year—we bring in an engineer, it

will take them about 3 years to bring them up to speed on the process and the technologies that actually exist, and they are always

changing. And that is if we keep them, we can retain them, because there are always opportunities being put forward.

That is all I have to say.

The CHAIRMAN. Thank you. It is especially interesting because of

the basic technologies, which I think is a key issue for us as a Nation, so I appreciate that.

[The prepared information of Mr. Lizotte may be found in additional material.]

The CHAIRMAN. I was just wondering, these were excellent presentations and gave me some strong background here, I am sure

Senator Murray, too, and these records will be available to others.

But I am wondering, Dr. Stupp, you mentioned the regeneration.

If you are a person out there today who has a spinal cord injury,

that is exciting news, but is it realistic news? I mean, what is the

time frame here when we move from the dream to some form of

actual reality, if there is such a time frame that is predictable?

Mr. STUPP. I think—well, it is probably reasonable to say that

this might happen in, say, 10 years, maybe five to 10 years. Five

would be very optimistic, but I think it is reasonable within 10

years.

However, the discovery by definition is not predictable and there

could be breakthroughs that will accelerate the process. I think

that it would probably come in stages, and so even earlier than 10

years, we may see very small steps that can be taken to at least

return some motion to paralyzed individuals. Maybe they won’t

have a normal life, but it will be slightly better than it is today.

The CHAIRMAN. And, Dr. Schloss and Dr. Dehmer, what should

we do in the area of funding? Is it more funding or is there more

focus? Should we reorient programmatic activity to accelerate Dr.

Stupp’s dream here, which appears to be just over the horizon?

Dr. SCHLOSS. One thing I would like to see us do is to be careful

not to too narrowly focus the funding. The things that Dr. Stupp

is describing, I think he has pointed out, rely on discoveries from

many different areas, and we don’t know exactly which of those

areas the solutions are going to come from.

I think what we want to do is encourage, as several people have

said, teams of investigators who bring expertise from a lot of different areas to be working together, to be communicating effectively—not just working in the same physical space, but communicating, so they can bring all of these ideas together.

That is why a number of us have developed funding mechanisms

and new programs that may not specifically focus on

nanotechnology, but focus on solving important problems in biomedicine. That said, sometimes those targeted on a medical problem funding approaches can tend to—what you end up funding

might be the most obvious next step toward solving a problem. We

have to be really, really vigilant about keeping an open mind to

leaps forward.

So that is, I think, one of the big challenges for the agencies, is

how to balance these various needs, where we have people who—

your question implied, I have the spinal injury now, or my daugh-
19

ter has a spinal injury now. I want to see a solution to that. We

have to balance the very obvious near-term research with the

things that may not come out for 10 years.

So it is challenging. I mean, obviously, more money is always

great.

The CHAIRMAN. Well, do you think there is a structure in place

at various NSF, NIH energy that is allowing for that sort of more

global view, or is there something that needs more attention?

Dr. SCHLOSS. I think there are things in place, and we are also

very aware that it needs more work.

Ms. DEHMER. I am going to agree with everybody. More seriously, I think what we are seeing is an evolution in the way science

is done. When I was in school and when my colleagues were in

school, we very rigidly fell into a chemistry department or a physics department or a material science or a biology department. The

entire science structure of the Nation, and that includes the universities, the Federal laboratories, and the funding agencies, have to

recognize that the problems are no longer defined by these tidy departmental names.

We have seen an evolution, no question about it. Sam is tenured

in how many departments?

Mr. STUPP. Three.

Ms. DEHMER. Three. And what are they?

Mr. STUPP. Chemistry, medicine, and material science.

Ms. DEHMER. And we are going to be seeing more of those kinds

of things. We are going to be seeing more students cross-train,

speaking a language that they didn’t speak in individual departments.

This is happening. Science is a pull that drags universities and

Federal laboratories and funding agencies along. But in addition,

the institutions and the funding agencies have to recognize what

is happening and be a push, as well. It is happening. It will happen

naturally, but everybody has to recognize that it needs nurturing.

The CHAIRMAN. I think Mr. Lizotte’s point also is—and certainly

Dr. Stupp’s point—is that you can’t do it without human capital

coming up.

Mr. STUPP. Right.

The CHAIRMAN. Is this technology so advanced in its need for

academic background that it makes it impossible, for example, for

us to educate average workers, people who are coming through the

system through a technical college system, to be contributors to the

manufacturing side, or does it gradate out like other sciences?

Mr. STUPP. Well, I think that certainly we will have to educate

workers on the manufacturing side, because once nanotechnology is

implemented in many products, there will be certain procedures

that have to be used. Clearly, that kind of—that group of individuals is not going to be the one making discoveries.

The CHAIRMAN. Right.

Mr. STUPP. So yes, there will be need for education at many different levels as the new technologies get implemented. But I think

the most important one right now, in 2003, if we think about how

we move forward, is to ask ourselves if we are doing everything we

can to encourage—to make science an exciting career for young

people. I mean, we need to ask that question very seriously.
20

I think the NSF, for example, does a lot of great things, but they

don’t have very much money. I mean, they spread themselves very

thin and sometimes they are not effective because the resources

aren’t there.

The CHAIRMAN. Of course, a big element of that is economic

return——

Mr. STUPP. Sure.

The CHAIRMAN. —which drives a capitalist society and draws

people in. How far are we from Mr. Lizotte being able to execute

on your ideas and initiatives in the nano area?

Mr. STUPP. Well, I think the nano area very much needs the

start-up company model to move forward, and I think you are beginning to see this culture develop. It is very difficult right now,

with some exceptions, to think about the right R&D programs in

the traditional large companies of this country. I think these technologies need to move out of the laboratory into very small startup companies that then slowly receive more and more investment

and then eventually are acquired, perhaps, by the larger ones, and

then products will be developed that way.

I think the start-up company culture is very important in

nanotechnology and we should do everything we can to promote it.

It also creates employment. It is very exciting employment for our

Ph.D. students, for example, because they are not excited about

going to the large—I don’t want to use specific names of companies,

but we all know which ones those are—they are not excited about

those jobs because they know they are going to be there solving

problems about existing products and they find that boring and not

challenging. Twenty, 30 years ago, they went to those companies

to do research and to introduce innovation and produce new products. That opportunity really isn’t there for them anymore.

So the start-up company takes a bright Ph.D., entrepreneurial

students and keeps them on that mold, and that has a very, very

positive impact. So it is a source of employment and a source of

wealth, because eventually real development takes place in those

start-up companies.

The CHAIRMAN. And Mr. Lizotte made some good suggestions

there. Did you have a comment?

Mr. LIZOTTE. Yes, I have a comment in regards to—as just a perspective. In the micro world, it was easy for me to transfer into,

back in the mid-1980s, in from a macro education into the micro

world very easily because there was the equipment was already in

place. All we were adapting was the existing infrastructure in the

semiconductor and microelectronics industry, and that had 60

years worth of development in the equipment end and the device

end.

I think we are at the—my belief, we are at this same situation

as these discoveries that are happening, and sorry for this terminology, and maybe at a test tube level or chemistry level, where the

thing is, is that the problem is those tools don’t exist. You don’t

have the equipment in place. So what is happening is you are making discoveries, but then you are saying, okay, well, how do I scale

this up and make it profitable? How do I make it into a product

and such? And that is the problem.
21

Back when I came into this marketplace, there was a full established discipline, so I could read and I could train and I could work

on that equipment and come up to speed very rapidly and make my

own discoveries over the years. In this case, there is no equipment.

It is you have got a discovery and you are struggling now with how

am I going to scale this up, and I see that as a big issue because

the new people coming in that might have some micro background

don’t have any equipment to jump on and focus on the manufacturing end of it. So I think it is going to be difficult, the translation

of this stuff back into industry. Maybe in the bio area, which there

is a lot of equipment out there in the bio area, but nanotechnology

as applied to maybe all the other markets, like materials and stuff

of that nature, I think it is going to be a hard time to ramp up and

bring into the marketplace.

Mr. STUPP. And that is exactly where I think the—why the startup companies are so important.

The CHAIRMAN. Doctor, you were going to make a point, Dr.

Schloss?

Dr. SCHLOSS. No, it is past.

The CHAIRMAN. OK. Unfortunately, we are going to have a vote

here in a minute, but let me ask one more question. To what extent

are we going to get down the road here 3 years and you are going

to have that capability of actually saying to somebody, well, we can

cure something very significant, whether it is spinal or cartilage or

whatever, and we run into an ethics problem? To what extent is

that a potential, and if it is a potential, how should we try to anticipate it and avoid it?

Mr. STUPP. Your question is about, are we going to run into an

ethical problem.

The CHAIRMAN. Right.

Mr. STUPP. It is not clear to me that there would be an ethical

problem. I think the only problem that I can see would be related

to the cost of the procedures and whether the population at large

would be able to afford them. I mean, they will initially be relatively expensive procedures, and so I think affordability might be

the issue.

The CHAIRMAN. Well, that is the issue throughout medicine today

already.

Mr. STUPP. Exactly. But at the same time, if you have, let us say,

joint disease, or if you have a spinal cord injury, the cost to the

government of an individual being afflicted with joint or spinal cord

disease is enormous. The cost of the new procedures that

nanotechnology will bring will be minute compared to what we currently spend. So there will be a need to balance those two, but—— The CHAIRMAN. You don’t see stem cell——

Mr. STUPP. Right. OK. The stem cell——

The CHAIRMAN. —a policy question here?

Mr. STUPP. OK. I would like to answer this way. Regenerative

medicine procedures, advanced ones which are based on

nanotechnology, will be possible with or without stem cells. Now,

so there will be advances that will not require stem cells. They will

be based entirely on nanotechnology.

There will be others that will require stem cells, and, in fact,

many of them will require combinations of the two. So I think the
22

best solutions in the long run will be those that utilize

nanotechnology and also look to stem cell biology. The combination

of the two, I think will be the most effective.

The CHAIRMAN. You were going to say something, Dr. Schloss?

Dr. SCHLOSS. No, I really agree, a very good answer.

The CHAIRMAN. Are there any other points folks want to make

on any of this?

Mr. LIZOTTE. Just one thing. I know there is a lot of debate and

there was a lot of stuff in regards to this nanotechnology and a lot

of books have been written and a lot of science fiction not involved

in biotechnology. I have never feared technology. I always say that

there are a lot of things that potentially can kill us out there.

I have been dealing with nano particles and stuff, debris from

processes I have worked on for the last 15 years and there are safeguards and infrastructure in there in which to alleviate any of

those concerns of small particles being ingested by humans and

this, that, and the other thing.

You are always going to have situations where somebody does

something wrong, but I think a lot of this technology is so beyond

the groups that might use things like this for things that are

maybe not so useful in society, but my feeling is a lot of this stuff

is science fiction.

The CHAIRMAN. I agree with that. I don’t see that as—I think

that threat, although it is represented, there are so many other

things that are very simple to do——

Mr. LIZOTTE. Right.

The CHAIRMAN. —that it would be unusual for somebody to pursue this.

Mr. STUPP. Senator Gregg, if I could just say one more thing, I

think there is enormous hype about the dangers of nanotechnology.

In fact, my community is trying very hard to eliminate that because the hype and the problem is really people that have, for some

reason, and it is very difficult to understand where this exactly

came from, where did it come from, but there is an enormous

amount of hype about the dangers of nanotechnology. They are

definitely not based on fact.

The CHAIRMAN. I think that is a problem the technology world

has that we continue to see, whether it is genetically modified

foods, which significantly improve production and reduce poverty

and reduce hunger being stopped by people who think they are

doing good, to science like this. We have to—I think as long as we

are transparent about it——

Mr. LIZOTTE. Right.

The CHAIRMAN. —and aggressive in being transparent on science,

that the average person is going to appreciate the benefits over any

threat.

Mr. STUPP. That is correct.

The CHAIRMAN. The key is for us that are in the public policy

arena and for you who are in the science arena to be constantly

pushing transparency so that people can’t make up conspiracy

theories——

Mr. LIZOTTE. That is right.
23

The CHAIRMAN. —based on some information that they think is

being hidden from them. And so that is why this hearing is, I

think, useful and will be covered.

I congratulate you on the science you are doing. I honestly feel,

and I think Mr. Lizotte made the point excellently, that we are not

as a nation going to be compete with China in basic manufacturing.

We are going to compete clearly in our capability of adding value,

and where we are really going to be adding value is in breakthrough science activity, and this is clearly one of them and you

folks are on the cutting edge, so you hold our future, not only from

a science standpoint, but potentially from an economic standpoint,

in your hands.

So please keep up the good work, and our committee is here to

try to be supportive and helpful, and if you think there are things

you need from the Congress, tell us. We want to react.

[The prepared statements of Senators Enzi and Murray follow:]

PREPARED STATEMENT OF SENATOR ENZI

Mr. Chairman, the application of technological advances in today’s healthcare is one of the key contributors to the longer and

healthier lives that most of us enjoy. Today’s surgical techniques,

for instance, make those of a generation ago look positively primitive. The current trend toward less invasive surgery allows people

to recover from surgeries more quickly, which gets them back to

productive pursuits more quickly, which is good for them, our economy and our society.

The application of nanotechnology in medicine has the same potential to move today’s healthcare forward by leaps and bounds.

Nanotechnology, however, is not the process of making current

technologies smaller—it is the science of building completely new

technologies at the molecular level.

Molecular devices will give us the ability to attack diseases and

conditions cell by cell. Imagine if we were able to fight cancer, for

instance, by targeting specific cells, instead of attacking broad

areas of tissue. The possibilities are limitless.

In May, I visited Ireland with the U.S.-Ireland Alliance. During

the trip, Congressman Xavier Becerra and I visited the

Nanotechnology Center at Trinity College in Dublin and learned

about some interesting areas of research.

One of these areas is nanofluidics—the engineering of fluid-carrying systems at ultra-small dimensions. Trinity College’s physics

and clinical medicine departments are collaborating in research on

advanced nanofluidics instrumentation for applications in medical

diagnostics and pharmaceutical industry.

From its research, the group at Trinity College has started a

spin-off company that will be located for the time being in the ‘‘Innovation Centre’’ of the college. The company, known as Allegro

Technologies, is specializing in the development of advanced instrumentation for high-throughput screening for applications that

pharmaceutical company could use in the development of new

drugs.

Interestingly, Trinity College screens its proposal for internal

funding in two ways. The first is through traditional ‘‘peer review’’

to determine the most promising possibilities for advancing our col-
24

lective knowledge base. The second is through attempting to determine the potential business applicability of the research. By putting each proposal through both of these rounds of scrutiny, Trinity

College demonstrates that it values basic research, but especially

the type of basic research that can lead to product breakthroughs.

As we look at nanotechnology in medicine, we ought to ensure

that both basic and applied research receive adequate attention.

Traditionally, the National Institutes of Health and other federal

agencies have funded business-oriented applied research through

their Small Business Innovation Research (SBIR) programs. I understand that we are already funding applied nanotechnology research through SBIR grants to small businesses, and I support

this, because our nation’s risk-taking small businesses will probably develop many, if not most, of the major breakthroughs in medical nanotechnology.

I commend Chairman Gregg for convening this roundtable discussion, and I look forwarding to working with him and my fellow

Committee members to make sure that the federal government

plays an appropriate role in supporting the development of

nanotechnology and its application in medicine and healthcare.

PREPARED STATEMENT OF SENATOR MURRAY

Mr. Chairman: I appreciate your efforts in putting together this

HELP Committee roundtable to discuss the emerging opportunities

presented through nanotechnology. The health care and job creation potentials for this field are truly exciting.

This innovative new technology provides new hope and possibilities for how we treat heart disease.

As all of my colleagues know, cardiovascular disease is the number one killer of men and women in this country. And in many

cases, it is a silent killer.

Devices that offer the possibility of destroying cancer cells without surgery could both improve—and save—lives.

Federal support for developing this new technology must be comprehensive, coordinated and innovative.

We need to enhance and grow existing biomedical technology and

infrastructure.

We need to ensure that federal agencies are ‘‘partners with the

research community’’—rather than competing for bureaucratic and

regulatory turf.

To achieve new technology breakthroughs we must increase our

support—particularly through appropriations to the research community.

This is a huge public undertaking, but it will have huge rewards

for health care and for high wage family jobs.

I appreciate the involvement of all of today’s participants in this

roundtable and thank them for their leadership in this area.

The CHAIRMAN. Thank you. We appreciate your coming by.

[Additional material follows.]
25

ADDITIONAL MATERIAL
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88

[Whereupon, at 11:27 a.m., the committee was adjourned.]

Æ