THIRTIETH MEETING

THE PRESIDENT'S COUNCIL ON BIOETHICS

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FRIDAY

SEPTEMBER 7, 2007

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The Council met at the Carolina Inn, 211 Pittsboro Street, Chapel Hill,
North Carolina, Chairman Edmund D. Pellegrino, presiding.

COUNCIL MEMBERS PRESENT:

[Edmund D. Pellegrino, M.D.,
Chairman](http://www.bioethics.gov/about/members.html)

Floyd E. Bloom. M.D.\
[Benjamin S. Carson, Sr., M.D.\
](http://www.bioethics.gov/about/carson.html)[Rebecca S. Dresser,
J.D.](http://www.bioethics.gov/about/dresser.html)\
[Daniel W. Foster, M.D.](http://www.bioethics.gov/about/foster.html)\
[Robert P. George, D.Phil.,
J.D.](http://www.bioethics.gov/about/george.html)\
[Alfonso Gómez-Lobo,
Dr.phil.](http://www.bioethics.gov/about/gomezlobo.html)\
[William B. Hurlbut, M.D.](http://www.bioethics.gov/about/hurlbut.html)\
[Leon R. Kass, M.D.](http://www.bioethics.gov/about/kass.html)\
Peter A. Lawler, Ph.D.

Gilbert C. Meilaender, Ph.D.

Janet D. Rowley, M.D.

Diana J. Schaub, Ph.D.

CONTENTS

Session 5. Nanotechnologies and Ethics: European and Global Perspectives

Henk A.M.M. ten Have, M.D., Ph.D. \...\...\...\.... 3

Comment by Peter A. Lawler, Ph.D. \...\...\...\... 38

Discussion by Council Members\...\...\...\...\..... 45

Session 6: Nanotechnologies: Science, Risk and Ethics

Richard Superfine, Ph.D. \...\...\...\...\...\...\... 73

Comment by Janet D. Rowley, M.D. \...\...\...\... 111

Discussion by Council Members\...\...\...\...\.... 116

Adjourn

[FURTHER PROCEEDINGS]{.underline} *(8:35 a.m.)*

CHAIRMAN PELLEGRINO: Good morning. This whole morning will be devoted to
the subject of nanotechnology and the ethical issues associated with
nanotechnology. Our first speaker is Dr. Henk ten Have, who is Director
of the Division of Ethics of Science and Technology of UNESCO. In
another part of my own life, he was my boss, since I\'m a member of his
International Bioethics Committee.

We\'re delighted to have him. I\'ve told Dr. ten Have we do not indulge
in long introductions, and he is relieved to know that as well. You do
have his background, however, in the book. So without further ado, Henk,
we\'re going to turn it over to you, and we\'ll have the opportunity
later for the council to raise questions.

DR. TEN HAVE: Mr. Chairman and members of the council, thank you very
much for the opportunity to speak on this topic. I will try to give you
an overview of the recent European ideas on ethics in nanotechnology and
try to broaden it also into more global perspectives.

I was lucky that recently there had been quite a few reports in Europe
an European countries on ethics in nanotechnology. The European
Commission in May 2004 published a strategy document. Subsequently, one
year later in June 2005, after an extensive and open consultation they
adopted an action plan for the implementation for a safe, responsible,
and integrated strategy for nanosciences and nanotechnologies going into
the time frame of 2010.

These documents are specifically interesting because they show that
there are two different types of concerns, at least at the level of the
European commission.

First of all, economic concerns. Concerted efforts are necessary in the
field of nanosciences and nanotechnology in order to address the needs
of citizens, and they are specific about these needs in public health,
energy, transport, sustainable development, but also to contribute to
the European Union\'s economic growth, competitiveness, and
productivity. And it\'s clear that Europe is worried that it is lagging
behind.

Global spending in research and development in this area shows that 37
percent is spent in the US, 28 percent in Japan, and only 24 percent in
Europe. The per capita investment in the 25 member states of the
European Union, and that is 2005 was 3 euros, compared to 4.5 euros in
the US and 6 euros in Japan. Private investment in Europe is even lower
with approximately 1.5 euros per capita, compared to 6 in the US and
more then 12 in Japan. Future spending will not significantly change
this picture even when total expenditures are increasing. So this is an
economical concern, and it\'s also interesting that it is closely linked
to the ethical concerns.

In research policy, as is argued in these reports, it is important to
ensure that ethical principles are respected, that social considerations
are integrated in the research and development process at an early stage
and that a dialogue with citizens is encouraged in order to safeguard
that citizens\' concerns and expectations are taken into account. And,
as I will try to show, this emphasis on involvement of citizens is very
strongly emphasized in all the reports.

To make sure that these concerns are properly addressed, the European
Commission announced that it will ask the European Group on Ethics in
Science and New Technologies to carry out an ethical analysis of
nanomedicine. The analysis will identify the primary ethical concerns
and enable future ethical review of proposed nanoscience and
nanotechnology research and development projects to be carried out
appropriately. That was 2005.

In the last few years, reports on the social and ethical implications of
nanotechnologies have been published in several European countries. An
influential role is played by the comprehensive report published in 2004
by the Royal Society and Royal Academy of Engineering in the United
Kingdom. It has separate chapters on social and ethical issues and on
public dialogue. It argues that most of the ethical issues arising from
applications of nanotechnologies will not be new or unique.
Nevertheless, when these issues arise they need to be addressed
seriously and timely. It recommends to fund interdisciplinary research
of the social and ethical issues and to introduce formal training on
these issues for all research students and staff working in the area of
nanotechnologies.

The report of the Health Council of the Netherlands in 2006 emphasizes
mechanisms of risk governance and public dialogue. It advocates to
establish a special national commission with representatives of science,
industry, and civil society in order to identify and communicate risks
at the earliest possible stage. This will also be I will come back to
that later.

The Federal Ministry of Education and Research in Germany published its
action plan in 2007, quite recently. The emphasis is primarily on the
economic concerns. Germany is number one in nanotechnologies in Europe.
About half of the nanotech firms in Europe are German firms. But ethics
is only briefly mentioned. What is needed, primarily emphasized in the
report, is an intensive social dialogue to inform the public about the
potential benefits and risks.

In France the report of the ethics committee of CNRS, the national
research organization, from last year is primarily focused on ethics,
but the emphasis here is on the responsibility of the scientific
community itself. What is necessary is *vigilance éthique*, ethical
vigilance. The report recommends concertation of all relevant
stakeholders, an orientation on ethics in all stages of the scientific
career, the development of ethics guidebooks for scientists, and the
establishment of what they call *espaces éthiques*, ethical spaces, in
research centers. Also, the National Ethics Committee in France has
earlier this year published its report, and it has a more philosophical
approach in the elaboration of ethical issues. It argues that the
dynamics of nanosciences and nanotechnologies are driven by the
interplay of two approaches, in fact two different models of
rationality.

First of all, the desire to intervene, to rearrange, and to reconstruct
matter, mastery through analytical decomposition, which is the classical
dream of engineering, or the *désir de controle*.

At the same time, there is a second type of approach rationality the
desire to synthesize and to make molecular objects capable of
self-assemblage and self-replication, which is a kind of approach to
make nature make objects more perfect, *désir d'emergence,* to overcome
the failures that are in the naturally given objects.

The European Group on Ethics in Science and New Technologies is a
neutral, independent, pluralist multidisciplinary body composed of
fifteen experts appointed by the European Commission for their expertise
and personal qualities. The task of the group, I think like your
council, is to examine ethical questions arising from science and new
technologies. It issues opinions, and the opinions need to be preceded
by a roundtable before the opinion is adopted.

The European published its opinion on the ethical aspects of
nanotechnology in and I can this is the opinion published in January of
this year, 2007. The emphasis is on nanomedicine, the application of
nanotechnologies in the area of medicine. The fundamental starting point
of the ethical consideration is that the interests of science are
legitimate and justified insofar as they are compatible with human
dignity and human rights. Protection of human rights is fundamentally
articulated in various European documents: the Charter of Fundamental
Rights, the European Convention on Human Rights, and the Oviedo
Convention, which deals explicitly with biomedicine and bioethics. Human
rights are rooted in the principle of human dignity. Together human
rights and human dignity, as it is said in the opinion, they shed light
on core European values: integrity, autonomy, privacy, equity, fairness,
pluralism, and solidarity.

The opinion, however, also introduces a broader perspective. It refers
to the United Nations Millennium Development Goals, arguing that there
is a moral duty to make affordable health care and biomedical
technologies available to all who need them on a fair and equitable
basis.

The European Group distinguishes several ethical issues in connection to
nanotechnologies, nanomedicine in particular. Similar distinctions are
made in the national reports but sometimes with different emphases, and
I will briefly discuss those considerations.

First is safety. The second is concerns about research ethics. The third
is the emphasis on public participation and involvement, and the fourth
is responsibility of the scientific community. And finally there are
some other ethical issues that are briefly dealt with in the reports:
the issue of legal implications, the issue of goals of development, and
the issue of social ethics.

Now, first the focus on safety. It is pointed out, in fact, in all
reports that concerns for safety are of vital importance. There is a
lack of data on possible risks. The European Group makes a distinction
between direct risks and indirect risks. Direct risks can emerge when
patients are undergoing an application of nanomedicine, for example in a
clinical trial or a medical treatment. Indirect risks are associated
with the possible harmful impacts of free nanoparticles on public health
and the environment, so-called nanopollution, and they can be harmful
for all individuals. In practice, it is impossible to draw a precise
borderline between the two kinds of risk.

The European Group argues that risk assessment, therefore, should be a
top priority. The lack of data is a cause of concern. There are
considerable difficulties, of course, because there are uncertainties,
knowledge gaps. There also is a difference between short-term and
long-term risks. There is also a more substantial difficulty because it
is uncertain whether the current mechanisms to identify, estimate, and
manage risks are adequate for these new technologies.

In the recent report of the French National Ethics Committee it is
stressed that enthusiasm among scientists to examine risks is rather low
until now. In 2005, only 0.4 percent of the total research and
development expenditures for nanosciences and nanotechnologies,
according to the report, have been used for research on risks. It means,
according to the committee, that there is first of all the temptation to
produce, to sell, to disseminate the objects rather than to study and
understand them. It is important to note that for the European Group
risk assessment is not only a technical issue. Safe governance of
nanotechnology is a key factor for the protection of human dignity and
autonomy of persons directly or indirectly at risk. This means that
assessing risks should take into consideration specific values. Here,
the Group argues, like both French reports and the Dutch report, that
the precautionary principle as a general risk management tool should
play a role. This principle applies when three conditions are occurring:
the existence of a risk, the possibility of harm, and scientific
uncertainty concerning the actual occurrence of this harm. In these
conditions, the precautionary principle requires to identify the
acceptable risk threshold, not the zero risk threshold, so it\'s not, as
I was reading in the proceedings of your June meeting, what Professor
Ferrari called the Prince Charles approach. It\'s not zero risk. It\'s
more what we can call the John Snow approach. John Snow was a medical
doctor in 1854 who removed the handle of the Broad Street water pump in
London in order to stop a cholera epidemic.

So it is necessary to identify the acceptable risks and to balance the
potential benefits as well as the potential harms, respecting the values
at stake. For example, human dignity. It\'s obvious that value judgments
play a role already in the determination what is a risk itself.

I know that the precautionary principle, there are a lot of discussions
essentially here. Maybe there is a big difference between the European
approach and the North American approach. In UNESCO we made a
publication on the precautionary principle, not to explicate it but to
explain what it includes and how it can be used. And maybe I can also
try to see if we can make it available for you, because here you notice
that in most of the European reports the precautionary principle is
emphasized as an important issue in risk management. And even in some
countries like France they have also included references to the
precautionary principle in legislation.

Now, in this perspective --- and I think also here it\'s important to
put the precautionary principle into a broader context --- a broader
approach to technology assessment is advocated. In addition to the usual
retrospective assessment, there should be a prospective technology
assessment at the national and European level, and the European group in
its opinion makes it clear you focus on safety in connection to
environment, public health, food; also security, the possible dual use
of technologies, impact on bioterrorism, military research, and on
social issues: impact on social and economical and institutional
structures. So those are issues that need to be taken into account in a
broader approach of prospective technology assessments.

This view has also been endorsed by a resolution of the European
Parliament, recognizing that a responsible strategy in this field of
nanotechnologies does integrate social, ethical, health, and safety
aspects into the technological development of nanotechnologies and
nanosciences.

The second topic of concern is research ethics. Nanotechnologies and
nanosciences will give rise to special ethical concerns in the field of
research. The European Group identifies the following areas where
problems can emerge.

First, research priorities. Nanomedicine can create new opportunities to
meet the needs of patients. But, as the European Group argues, the
overall goals of health-related research must be seen in the context of
fair distribution and the overall goal of alleviation of the global
health status. So it\'s not only that you can look at research itself,
but it is taking place in a broader context, and ethical questions
should therefore be raised concerning the criteria used in priority
setting.

It is also argued that the current emphasis on commercialization,
patenting, private gain derived from research, especially when research
is funded by public money, raises the issue of the fair sharing of
burdens and benefits. There is also a need to clarify the ways in which
public investments in this area --- and most of the investments are in
the public area --- will benefit the citizens of Europe. The Group again
refers here to the UN Millennium Development Goals. So not only the
citizens of Europe but, as said earlier, the global health status should
be taken into account. Obviously they don\'t explain what kind of
criteria for research priority setting should be used or can be used.
It\'s a little bit of a general statement here.

The second area in research ethics is more specifically concerned with
clinical medicine. Several ethical concerns are raised in regard to
clinical research, problems as informed consent. In the context of lack
of knowledge and uncertainties it is difficult to provide adequate
information and to obtain consent. It will be necessary to develop new
methods of providing information, not to qualify the principle of
informed consent but to try to find new methods, new approaches of
providing information. But, again, here the group does not provide any
suggestions.

Another issue is ethical review. Researchers have the responsibility to
make sure that adequate ethical review processes are carried through for
studies of nanomedical devices when it concerns human beings. In this
context it is recommended that there should be a better information
exchange between research ethics committees in the European member
states.

And then also the issue of privacy is raised. Privacy is a concern
because in all the reports when information is obtained by new
diagnostic methods it can be can be used by third parties, but again
here there is no detailed elaboration of how the issue can be addressed.

In general, possible solutions to these clinical research problems
require serious interdisciplinary research. Like has been done in the
context of the Human Genome Project, a considerable amount and the group
suggests 3 percent of the budget for research in the European Union
should be reserved for research on the ethical, legal, and social
implications of nanomedicine, what they call NELSI. This research need
better coordination and cooperation. Not only should there be some kind
of NELSI projects, but there should also be a European network on
nanotechnology ethics, also one of the specific recommendations made by
the European Group.

Such research should have a broader perspective than merely going into
the clinical ethical issues. Studies should also focus on the more
fundamental issues, in particular on the philosophical and
anthropological questions raised, for example concerning individual
responsibility, the concept of the self, personal identity, societal
goals of research, and global healthcare. One of the basic questions,
for example, is how our concepts of human being will change under the
influence of nanotechnological developments.

At the same time, the French National Ethics Committee, although it
itself extensively addresses philosophical questions, gives a warning.
The philosophical questions of *l'homme-machine*, which is important in
the context of nanotechnology --- they are important, but they should
not be used to hide or to cover up the more urgent ethical issues
related to the introduction, what they call the "subterranean
intrusion," of nanoparticles, which is mainly driven by technological
performance and commercial interests. So there is a need to focus, first
of all, upon the questions concerning nanoparticles because it\'s
already there, and then of course we should not forget to focus on the
philosophical questions. But we cannot use the philosophical issues as a
kind of diversification strategy.

The third area of ethical concern has to do with public participation.
All European reports so far agree on the need for more and better
involvement of civil society. The European Group explains that there are
two reasons for this focus on public involvement or participation.
First, Europe is characterized by pluralism with a tradition of mutual
respect and tolerance. Deliberative democracy requires a culture of
debate and communication.

Secondly, nowadays there is a need for trust and confidence building
between the scientific community and the public. It is important that
the involvement of the public in the debate on nanosciences and
nanotechnologies is focusing on uncertainties and knowledge gaps, not
only on safety issues but also, for example, on policy choices such as
the funding of research and development, the goals of scientific
development.

The involvement should go beyond informing the public as if this is a
prerequisite for effective marketing of commercial products. What is
needed is transparency and openness, not only on the possible benefits
but also on the harms and risks, even if uncertain and unknown. What is
interesting, they also refer in this connection not only to risk
management but also to benefit management. In order to create more
realistic views among the pubic of the prospects of the new
technologies, it is a challenge to find a middle road between hype and
justified optimism and pessimism.

Several models of public dialogue have already been developed and
tested, such as, for example, the nano juries in the UK and a program of
what they call nano trucks in Germany, where they go around the country
with trucks with information about nanotechnology.

But there is also a need for developing new methods of engaging the
general public about issues raised by technologies. The European Group
makes several proposals. They want to prepare surveys of public
perception of the benefits and risks of the applications of
nanotechnologies. They want to create a European website on ethics and
nanomedicine. They want to organize public debates as a kind of road
show in different countries. And what is also important is they want to
give attention to the question of labeling nanomedical products. And
here you see also perhaps one of the historical lessons in Europe with
genetically modified food in particular, that there is a lot of public
mistrust about technological developments. At least what you can do is
to inform the public whether or not some products contain genetically
modified components, and here it may be the same for nanomedicine. But
if you want to really be open to the public, you have to indicate
whether nanomedical products are included in the objects that are
available.

The European Parliament has supported the proposal of the European
Commission also to set up special ethics committees in this area. They
can provide independent scientific advice and help ensure that the
public is properly informed, creating a climate of trust. But it is not
so clear whether these will be separate committees specially for
nanotechnology or that the mandate of existing committees will be
expanded. But it is important that here obviously we are thinking about
a kind of bully that can mediate between scientific claims and the
public in order to make sure that the information that is provided about
risks, about benefits, can be trusted and is not exaggerated by the
scientific community.

These kinds of committees can also be a kind of motor of public
involvement and public debate. The emphasis on public involvement is not
without problems, as is also discussed in several of the reports. The
French National Ethics Committee discussed the disconnection between the
discourse and the reality of the nanocosmos. There is much talk about
the revolutionary development of nanosciences for the treatment of
diseases that are incurable today, but for the moment there is only and
that is what the public will perceive there is only new paint, new
textile, and new cosmetics using nanomaterials.

This situation --- I think it is important --- resembles that of the
development of GMOs and gene food. Ideologically, the discourse here was
very much focused on idealistic goals like eradicating hunger in the
world, but the actual products and the public very well knows it the
actual products were marketed in the interests of the agro-industry
companies of the rich countries. So there is a disconnection between the
discourse that is focused on eliminating very important problems and the
actual reality.

Also the reports on nanomedicine and ethics in the Netherlands
elaborates the point that scientific research can only prosper if there
is a climate of trust in society. This is not only a matter of informing
the public. It is vital that science itself subjects itself and its own
performance to continual critical reflection. What is true for science
is also true for institutions such as government agencies, policy making
bodies, research organizations, and companies.

Again it is reiterated that lessons should be learned from the
problematic introduction of genetically modified food in Europe. It is
clear that many misperceptions about public opinion exist. Scientific
and technological knowledge among the general public is limited indeed,
but it does not mean that concerns about a technology are due to lack of
knowledge or incorrect information. Concerns, therefore, cannot be
removed through scientific education and information. On the contrary,
there are indications that more knowledge and information promotes
skepticism and polarized views.

Of prime importance, as the report is arguing, is free choice,
transparency, and personalized information. The public knows very well
that it is necessary to balance the harms and benefits. But at the same
time the public has the impression, at least in quite a few European
countries, that they never hear how this is done and that their views
are really taken into account. They therefore are suspicious that in the
end economic interests are more important in policy making and risk
management than idealistic considerations concerning health and the
environment. And of course we have affairs like BSE, mad cow disease,
dioxin intoxication. They have not so much illustrated a lack of
knowledge and information about biological processes among the public,
but rather they have illustrated failing institutions, carelessness,
incompetency, lack of resources, and even fraud. So experts\'
declarations denying or downgrading risks create more confusion and are
in the eyes of many citizens disturbing and unreliable.

Instead of strategies to make the population more rational and inform
them about developments, which is necessary, of course, but instead of
only focusing on making the population more rational, also institutions
should pay more attention to their own conduct. Trust must be earned by
expertise, performance, integrity, openness, and accountability.

The recent Eurobarometer one year ago, which is a survey of citizens\'
views in all European member states, is a little bit confirming this
picture. When asked whether nanotechnologies will improve our way of
life in 20 years\' time, 40 percent of the respondents in European
countries replied positive, 5 percent negative, but 42 percent did not
know how to answer. On the other hand, support for nanotechnologies,
whether the technology should be encouraged, totals 55 percent, varying
between 33 percent in Ireland to 72 percent in Finland. So the majority
view among European citizens, 66 percent is positive and without concern
that the technology is risky. If you compare it with surveys in the US
and Canada, Europeans consider nanotechnology as more useful for society
and have greater confidence in current regulatory arrangements.

The fourth area of discussion in European reports is focusing on
responsibility of the scientific community. The French National Research
Center report in particular emphasized that a fundamental transformation
is necessary in the mentality of researchers. In the area of research,
ignorance or reluctance often prevails in relation to ethics. The
awakening of ethical reflection on science and technology is not a
one-time, incidental event introduced by ethics specialists but a
long-term effort focused on and sustained by all researchers. This is
what they call *vigilance ethique*. It demonstrates the responsibility
of the scientific community itself. This is the counterpart of
transparency, the clarification of information and involvement of the
public, involvement of the public at the same the responsibility of the
scientific community.

Transparency as well as responsibility is required because
nanotechnologies are developing in a social context that is sensitive to
problems emerging from scientific and technological progress. Again, it
is not only a matter of researchers explaining the results of their
research but of showing that researchers themselves take into account,
are aware, and sometimes worried about the possible implications for the
life of citizens and society in general. The scientific community is
therefore faced with three challenges.

First, they have to rethink the ethos of research. The changing
conditions and social structure of science makes it necessary to
redevelop, to rethink, the existing codes of conduct and to promote
ethics education. The current ethical system exemplified in codes of
conduct is no longer sufficient. Researchers have to take care that they
themselves, they make and reiterate, rearticulate, revise their codes of
conduct.

Second, there needs to be an emphasis among researchers themselves on
prevention and precaution. Reflection on the possible consequences of
research results should pay more attention to prevention of risks. This
is not only limited to nanoparticles but should also consider the
possible long-term impact on the individual and society. That is a duty
of the researchers themselves. It cannot be delegated to specialists
like ethicists, but researchers themselves should show that they have
this concern. The same responsibility requires precaution in the face of
uncertainties.

Then third, there is a need for reflection on values and ends. Given the
political and commercial interests in which nanotechnology programs are
stimulated, it is difficult to maintain, according to the French report,
the neutrality of sciences. Scientists themselves should therefore
reflect on the values underlying their work. Nanotechnologies in
particular transcend fundamental cultural values such as the
distinctions between natural and artificial and between natural and
cultural. There are also important questions of meaning that every
researcher should address: Why this research? What is its purpose? Who
will benefit from it?

In order to take this responsibility of the scientific community
seriously, a sustained effort is needed to inculcate ethics throughout
the careers of researchers. This should start in their early education
and continue in their training, the formulation of projects, the
laboratory work, and the evaluation. The aim is to make scientists
themselves more reflective and to create spaces for ethics, *espace
ethiques*, within the daily business of research.

Then the are some ethical issues that are briefly addressed in the
reports. For example, the issue of legal implications. The European
Group does not propose new regulatory structures. What is necessary in
its view is, in first place, to monitor developments in order to make
sure that regulatory systems do really occur --- all developments,
especially concerning nanomedicine products. And, secondly, that it is
necessary to implement existing regulations.

A second issue that is briefly address is concerning the goals of
nanotechnology. The European Group points out that the distinction
between therapeutic goals and enhancement goals may become less clear
with the development of nanomedicine. It emphasizes that it is important
to maintain the distinction between medical and non-medical uses.

Then third, social ethics. In many European reports it is stated that
nanotechnologies are not only significant for individuals but have
consequences for society as a whole. Nanotechnologies will furthermore
have global consequences. They will influence the use of natural
resources and the distribution of wealth. They can potentially
contribute to the creation of a more sustainable society, promote the
health of future generations, and therefore help to realize the
Millennium Development Goals.

However, as is pointed out in the Dutch report, without consistent
efforts to translate technological developments towards the
circumstances of developing countries, it is unclear whether these
countries will enjoy the benefits of technological progress.

The European Group distinguishes two aspects in the issue of equal
distribution. First, intergenerational issues. They concern the
distribution between current and future generations. Particularly the
problem of sustainability is important here. Applications of
nanotechnology can promote better use of natural resources and energy,
water purification systems, and removal of waste. This would be
important for future generations, but at the same time more knowledge,
of course, is necessary concerning the environmental impact of
nanomaterials themselves. They will be important also for future
generations.

The second issue here is intergenerational questions. They concern the
distribution among present generations. This is the problem with the
possible use of nanotechnologies to address the needs of the developing
world. It is unclear whether developing countries will really benefit.
At present, for example, vaccination is available for many diseases and
relatively inexpensive but nonetheless infrequently used. Because the
driving forces of technological development are primarily focused on
developed countries, the materials and objects produced are first of all
in the interest of people in these countries.

This brings me to discussing the more global perspective, as is also one
of the tasks of UNESCO. From a global perspective, we need to be sure
that ethical reflection also discuses the benefits and harms in a wider
perspective.

In early 2004, UNESCO's World Commission on the Ethics of Scientific
Knowledge and Technology decided that nanotechnology was a subject
meriting UNESCO's attention due to the enormous potential benefits, but
also the challenges to regulators, scientists, and society at large.

As one of the first UN agencies, UNESCO started anticipatory studies
concerning ethical and social impacts of nanotechnology and its
applications. The subject was first explored during the meeting of the
world\'s ethics committee in Rio de Janeiro in 2003. It was further
discussed in the next meeting in Bangkok in 2005. With the aim of
mapping the ethical dimensions of nanotechnology from a global
perspective, a multidisciplinary group of experts on ethics and
nanotechnology was established later that year with the participation of
ten experts from nine countries.

The expert group set up a twofold strategy. The first phase involves the
preparation of a state-of-the-art study on ethics and nanotechnology.
The aim of this study is to explain what kind of ethical issues are
related to the development of nanotechnology so that policymakers, and
especially policymakers in developing countries, will have a better idea
of the challenges. As a result of this, you will have the brochure on
the ethics and politics of nanotechnology that has been made available
for you.

It is important to be aware that in most of our 192 member states, there
is, of course, no development in the area of nanotechnology, and many of
the policymakers are not very much aware of the possible impact of this
technological development for their own country. But nonetheless, all
countries will be confronted with the potential impact of this
technology in the near future. So the brochure is trying to explain. It
doesn\'t take a position. It tries to explain that this is an important
area of concern.

The expert group also engaged in a more fundamental study of the ethical
issues. They met several times in Paris, they prepared papers, and
finally they have published a book on ethics and nanotechnology, which I
will also make available for you, which is a more in-depth explanation
of the ethical issues involved.

Then finally the ethics committee, the Word Ethics Committee, also tries
to deduct from the studies the potential activities that could be
undertaken by the member states of the organization, policy
recommendations that has just been published two weeks ago, which is a
number of policy recommendations for the member states of UNESCO. The
policy recommendations, they focus at least on four areas. One is the
need to articulate the ethical framework. It is argued that further
reflection is needed on the ethical principals that could guide the
development of nanotechnology. And here in UNESCO, of course, the
example is a recently adopted declaration on bioethical principles. This
is a declaration on bioethical principles that has been unanimously
adopted by all member states, and it\'s the starting point for many
activities in the organization in the area of bioethics.

The question is whether the set of bioethical principles can also guide
the development nanotechnology, because nanotechnology is much broader,
it seems, than only the area of nanomedicine bioethics. But further
explanation is necessary to see whether there can be a framework of
ethical principles that could help guiding the development of
nanotechnologies.

It is also argued that there is a need for capacity building in member
states, maybe a need for special bodies to deal with the ethical issues
in member states, as has been explicated by the European Group.

The second area of recommendations is that there is a need for
awareness-raising and debate. It is necessary to create public debates
to focus on the environmental impact on those issues that are better
mechanisms for risk analysis. So all these issues are also explicated to
help specifically developing countries to prepare themselves for this
scientific revolution.

The third area is emphasizing the need for ethics education. There is a
general need for ethics education, but especially like the French
committee has argued it is necessary for research in this area, not only
for research in medical schools but in fact for all scientists who are
incorporating into this endeavor of nanotechnologies.

And then finally it is emphasized there is a need for research and
development policies. More scientific and technical knowledge is
necessary. It is necessary to involve the social scientist in studying
this area of science.

It is necessary to start and the same is advocated here to start into
this research on the social, ethical, and legal issues. And it is also
necessary to focus specifically on the link between nanotechnologies and
the concept of development. What does it mean for developing countries
that these technologies are developing? And there is a need to have a
debate on the goals of this technological development, goals that could
be related to the framework of the Millennium Development Goals.

Now, these recommendations have now been circulated among the member
states of UNESCO policy-making bodies, and in October there will be a
general conference of all the member states, and then we have to wait
and see which kind of activities the organization can undertake in the
near future.

Now, summarizing, nowadays the possible benefits and harms deriving from
nanotechnologies are increasingly discussed, also the implications for
international relations in science and technology policies. Many
initiatives are being carried out in order also to provide an early,
informed, and interdisciplinary public debate. It is expected, and
especially strongly emphasized in the European reports, that these
activities be able to preserve or sometimes restore trust in science and
technology. This is especially relevant because in order to maximize the
benefits of nanotechnology it is also necessary to anticipate and
discuss the possible eventual risks. Academic researchers, developers,
potential users and other important actors need to be involved in this
trust-building exercises in order to ensure that there is an adequate
representation of societal forces included in this effort so that the
future of nanotechnology is not only shaped by researchers or
policymakers but in fact by the general public as such.

The failure to have such a broad and inclusive public debate and
involvement is to a large extent, at least in the European context, the
cause of criticism and public mistrust. Several issues in the past, like
genetically modified food, animal experimentation, crisis in the agro
industry, this is causing criticism and public mistrust regarding
scientific advancement.

At the same time in a global perspective, there is also increasing
concern that all countries should be able to benefit from scientific and
technological progress, especially developing countries and those
developing countries that at the moment are not involved in the
nanotechnology revolution. Rather than emphasizing the particular
European perspectives they do that, but they go beyond it. Policy
reports in Europe seem to raise the question how Europe can contribute
to make nanosciences and nanotechnologies relevant and beneficial for
humankind in general.

This global perspective, I think, opens also opportunities for
international organizations such as UNESCO. You know, it\'s the only UN
organization with a mandate in the area of sciences. I think UNESCO can
take up the challenge and assist member states and policymakers in the
development of nanotechnologies contributing to reach the Millennium
Development Goals.

Thank you very much.

CHAIRMAN PELLEGRINO: Thank you very much, Dr. ten Have. Dr. Peter Lawler
has consented to open the discussion. Peter?

PROF. LAWLER: This is not a contract but a covenant. I consented to do
this out of ignorance. I know this is a very important topic. I thought
maybe the counsel should take it up but not because I\'m the world\'s
leading expert on it but because it\'s something I think, as an alleged
expert on bioethics, I should know more about.

In your fine presentation, you talked about democratic control,
technology governance, that public deliberation should control the
development of biotechnology with human dignity in mind, human rights in
mind, with health and safety in mind. And in order for deliberation to
be effective, we have to avoid the two extremes, the one extreme of
nanohype, or falling victim to wild promises and letting those wild
promises distort research agendas and so forth, but also nanofear, or
Prince Charles disease or any introduction of an uncertainty into the
world is to be avoided and so let\'s not do anything.

And so in the same way we have to distinguish between near- term uses of
biotechnology, things which were already going on in paint, textiles,
food, cosmetics, and drugs. And the more advanced and visionary views of
nanotechnology in terms of a basic transformation of the world and how
we view the world.

But I\'m not so sure we can separate the near term from the visionary,
precisely because the visionary is so astounding yet so plausible. The
experts disagree --- and I have no idea who is right --- on whether
molecular manufacturing is right, these self-replicating machines that
will build things from the bottom up atom by atom. And that does seem a
bit farfetched to me.

On the other hand, they actually, when you look carefully, seem to agree
that the goal of nanotechnology is the complete control of the physical
structure of matter, and this genius Fineman in the later 1950s wrote
that the principles of physics do not speak against the mastery of
things atom by atom. And I think the scientists don\'t disagree on this
as a prospect, they just disagree on how it might be done.

And so public education here becomes sort of a problem because it
depends on knowledge of what\'s possible, knowledge of basic physics,
which is not so basic --- basic not in the sense of easy but basic in
the sense of fundamental --- and a knowledge of basic chemistry, which
again is not so basic.

So it\'s not so clear to me. It seems to me a big issue whether there
can be public control, democratic control, of the progress of
nanotechnology, especially in view of one thing I think you didn\'t have
time to mention, and that is the inevitable military use of
nanotechnology, the inevitable arms race, all sorts of weapons
possibilities. Weapons that are smaller or smarter or more precise,
easier to use.

Now, the article you gave us by Schummer says very truly military uses
shouldn\'t distort science, but military uses will distort science, and
won\'t the arms race here produce nanotechnological rapid developments
which will have applications in many other areas of life. And so there
probably will be an arms race between the United States and China with
nanotechnological implications. Bioterrorism --- we\'ll have to have a
defense against it, and a defense against bioterrorism will cause
another kind of nanotechnological arms race.

So isn\'t it true in the long term if we reflect on this, we have to
reflect on the fact that nanotechnology is necessarily going to
introduce into the world irreversible processes which we may or may not
be able to control? This is like a huge problem to me. So Prince Charles
isn\'t simply nuts to worry about this.

So we have the paradox that greater human control will produce greater
uncertainty about what is actually going to happen. And we also have
reason to worry and be hopeful about the possibility that nanotechnology
or the likelihood that nanotechnology will allow us to take control of
living materials in the capacity for self-organization, will actually
bring this self-organization under our control.

This is will change not only our understanding of life but sort of what
life is, which you alluded to, but I think it\'s a real problem. So
shouldn\'t we up front be studying and trying to understand these
changes with the candid recognition that we will probably be unable to
prevent them if they\'re possible.

So with respect to all the problems you mentioned so well, the
environment. You could understand the possibility of environmental
devastation either through bioterrorism or the unintended consequences
of attempts to control the environment. You could also anticipate a
complete solution, or almost complete solution, to the environmental
problem. We\'ll be able to solve a unique human need with a lighter and
lighter touch on the actual environment. This might also be possible.

With respect to the economy, there could be global displacement. The
world could be divided into the nano haves and the nano have nots.
Natural resources could become more or less irrelevant with horrible
consequences, perhaps, for developing countries.

On the other hand, maybe we could conquer scarcity. Not only will things
become sustainable but finally we\'ll achieve the Marxist dream of
having plenty of everything with very little work.

In the same way, with respect to health, some of these experts seem to
now understand disease as simply unfavorable molecular configurations
that we can change. And then the experts who write against this seems to
say, well, not all diseases. That won\'t apply to anorexia, which I
guess. So there are some diseases that can\'t be understood this way,
but maybe plenty of diseases can be understood this way.

And then you have things I\'m not competent to go into: enhancement.
This line between health and enhancement should be maintained but it may
be tough to maintain because enhanced people may be more healthy people,
in fact. Then you have to the two areas: physical enhancement, which
could be basically a good thing, but then you have cognitive
enhancement, which becomes a problem for all sorts of reasons.

And then you have what to me might be the biggest issue finally, would
be the total eradication of privacy where you have a capacity to store
huge, an almost infinite amount of information on every particular human
being and a sort of intimate surveillance of every human action. I think
this is really possible.

So what we have here is a possibility of human beings coming to be
understood as just complex molecular structures and nothing more, so you
have the world where some complex molecular structures are transforming
other complex molecular structures, and this turns out to be a very
fundamental question of philosophy, which depends upon answers to very
fundamental questions of science. And it also depends upon, I think, a
certain inevitability of what can be done being done. And it\'s hard for
me to see how all of this can remain under democratic control, proper
deliberation and dialogue, and all the good things you talked about.

So should our council jump in early on this not so much because of
what\'s going on now but what will likely happen in the long run because
of the promise of nanotechnology.

CHAIRMAN PELLEGRINO: Thank you very much, Peter. Dr. ten Have, do you
care to respond?

DR. TEN HAVE: I think what is interesting in the development of
nanotechnology is that it makes particularly acute two very old basic
questions concerning science. One is, as you mentioned, how should we
assess technological development? Is it autonomous, or can it be
influenced? And that, of course, is not a new question, but because of
the rapid evolution of nanotechnologies it is becoming more urgent.

And you can say, well, of course this development is really autonomous.
It can hardly be influenced, and it will go on. And then the only thing
you can do is to resist it or to comply. And that is precisely what you
can notice sometimes in European context, that you have all kinds of
groups having this view. And the only thing we can do is resist it.

Every summer you have groups burning fields of genetically modified
crops, and they are arrested by the police, they are burning down
McDonald\'s. That\'s the only thing you can do. You can also say
scientific development is the result of choices made at some levels of
policy making, and the choices should be influenced by values. There is
not an autonomous process, but we deliberately allocate money for
particular developments, especially in medicine.

Maybe there are some developments that are really autonomous. For
example, most of the products in France, they are using nanomaterials in
cosmetics. L\'Oréal is very active in having any control, and now people
are arguing maybe there should be more control, more safety studies done
on the nanomaterials brought into use through cosmetics. So I think this
is a basic question here in how scientific development can be influenced
and where are the value choices made.

The second basic question and I think it has become more acute during
the last 20 years is concerning the ethos of science. What does it mean
to be a scientist? What kind of responsibilities do you have? And I
think that is very well addressed in the French report. The Mertonian
system of values is no longer working very well. But what is the
alternative? What are the values that scientists themselves should
address? Where is the organized skepticism that is important for being a
scientist, because we hear all these claims of people and, of course,
this is not only in the context of nanotechnology because people
remember the Korean case. There was a case with a Norwegian doctor and
all kinds of cases illustrating that science is more driven by
commercial and other interests than by a value system of its own.

So that\'s why it is important also for the scientific community to make
clear that they have a value framework. They need to make it clear
because otherwise they will lose the rest of the population, and that\'s
a concern in the European context, that science is not an activity in
itself but is an instrument to benefit society as a whole, the
community. So scientists should show that they earn the trust of the
public by showing themselves more concerned about the developments. And
that\'s also why scientists sometimes are now criticizing each other,
because they make unsubstantiated claims in public about what
nanotechnology can do. And they say we should be more careful, we should
be more skeptical, we should be more critical about our own work.

But these are also --- those are two basic questions concerning
technological progress and the ethos of science that are now more acute
in the area of nanotechnology, and they will require more adequate
reflection.

CHAIRMAN PELLEGRINO: Thank you very much. Now open to the members of the
council. Alfonzo? PROF. GÓMEZ-LOBO: I have an information question, but
let me explain a little bit what my worry is. I understand our body to
be a body devoted to the study of bioethics and to clarifying bioethical
issues to the American public and to make recommendations to the
American administration. Now, as I\'ve understood our task, what we\'ve
tried to do is to clarify issues that are disputed. For instance, there
is the ethical question, is it morally right or morally wrong to clone
humans, for instance. Would it be morally right or morally wrong to set
aside the dead donor rule?

I think those are the kinds of ethical questions we\'ve been asked to
address, and I\'m a little bit lost in the case of nanotechnology as to
what are the disputed ethical questions such that we would we should
engage in reflection and examine the different positions and perhaps
have, you know, either a unanimous recommendation or a split
recommendation. In other words, from what I\'m hearing, there are, of
course, risks involved with nanotechnology. But, of course, if there are
risks they are risks for harm for humans. It\'s fairly clear that it
would be morally wrong to engage in the production, say, of certain
nanotechnological materials that would cause harm. But I don\'t see it
as an ethical problem. I think the ethical problem is clear.

Now, many of the other problems you mentioned, Dr. ten Have, seem to me
to be extremely important, but I view them more as issues in politics or
issues in general prudence, things that should be done, for instance, to
re-insert science in the political community, for instance, to
regenerate trust. But, again, I\'m not maybe I\'m blind to this. I
don\'t see the specific ethical issue that would require reflection
which solutions are correct and which are incorrect.

I would be grateful for some clarification on those points.

DR. TEN HAVE: Of course, it depends on, of course, how do you demarcate
the area of ethics. And I think that it\'s a kind of also in UNESCO it
is often argued that risk is a technical issue, it doesn\'t involve any
ethical issues. And if you talk about the social ethics, it\'s more
political. I think what is at stake in both is reflection on the values.
So ethics is not only using an algorithm of principals, but maybe we
don\'t know exactly which are the principles that should guide a
particular development but are important values involved, which is more
or less also the strategy in the European opinion to say, well, we have
value and respect for human dignity.

We don\'t know exactly how nanotechnologies are impacting on human
dignity. At the same time now technologies can contribute to promote
health. This is an important value. And the reflection is ethical. Also,
if you want to focus on risks as they are doing now in, for example, in
OSED, you still have to define what you consider to be a risk or not,
and it\'s related to what do you see as a significant harm? And this is
not a technical issue. It\'s a kind of balancing of different levels of
what is acceptable, what are benefits, what are harms?

So in the end it\'s an ethical issue that will be translated in very
technical details. The same for, let\'s say, the question about the
responsibility of scientists. To my mind, that is a basic ethical debate
that needs to be encouraged by governments but is mainly the
responsibility of scientists themselves. In what way are they honest?
Are they showing integrity in explaining the research they do, in
reporting the results? And it\'s not legal. It is a duty that you need
to have in order to be a scientist in distinction to people with other
professions. So it\'s maybe also here a kind of not only do you have the
professional ethics of medical doctors, you also have the professional
ethics of scientists. And that is ethics.

So in my view, ethics is broader in a sense that it concerns a
reflection on the values that are at stake.

CHAIRMAN PELLEGRINO: Dr. Schneider and Dr. Dresser.

PROF. SCHNEIDER: A couple of times you mentioned proposals to educate
scientists in ethics. I\'m curious to know what that means in real life.
There is a lot of discussion of educating scientists so that they can do
human subject research in the United States. What that means is somebody
has to decide what the right thing to think ethically is, at least this
is how it works out in practice, and instruct scientists on the correct
way of thinking about the ethics of their undertaking. And then in order
to be sure that this education has been effective, scientists have to
take a test, and the test, which is often done on the Internet, measures
how well they have learned their ethical lessons.

The tests I have seen suggest that the authors of the test are very
confident about the correctness of their ethical views and that their
ethical views aren\'t very complicated. So what does this proposal for
educating scientists about ethics work out to mean in real life?

DR. TEN HAVE: You know that there is a lot of ethics education in the
area of bioethics, primarily in medical schools, and in UNESCO we are
trying to make a database of ethics teaching programs in different
countries and different areas, not only bioethics. But there is a
tendency, I think, in many countries to reduce ethics teaching in the
area of bioethics to primarily research ethics, and I think maybe I\'m
wrong, but Dr. Pellegrino told me some time ago that at the moment in
your country here there is less ethics teaching, in fact, than 20 years
ago. And the number of programs have also been concentrating on a more
limited area of research ethics.

If you look at other countries, and especially in Europe, it is not so
well developed. In France you don\'t have a lot of ethics teaching, even
in the area of bioethics. In other countries maybe it\'s a lot better,
but in most of the European countries ethics in general ethics teaching,
even in the areas of bioethics, is not well developed. So we try to
promote, and what is also explicated in the reports, is that in fact it
is necessary to have ethics introduced in the training, in the
curricula, of all scientists.

And then there are different ways to do that. One way --- and you
pointed out --- is instructing scientists what are the rules, what are
the codes of conduct, and what do they have to learn in order to behave
properly.

That, I would say, is a view of ethics as it is used also in companies
where you say, well, you have to follow particular rules and then it\'s
okay. But what I usually try to argue, especially also in the French
report, is ethics is not instructing, it\'s more making scientists
reflect on the implications of their work and to think about the value
choices that they are making, that they are promoting, in their types of
research without sometimes having clear answers. But you can communicate
your own uncertainty and your own difficult choices in a way that shows
that you are concerned with the implications even if you are not
completely certain. And if you can do that as a scientist, you can also
better communicate, perhaps, with the public.

So they try to introduce ways of teaching ethics, for example, not by
instructing or lectures but by giving them assignments, by small group
teaching, by discussion, because the primary aim is to make scientists
aware that they are not only like engineers and even for engineers it
would be important, not only having a technical job but their work is
taking place in a context and will have social implications; and it\'s
their duty to think about that, and they have to learn how to analyze
those problems and how to reflect on those problems and how to
communicate those issues.

So I don\'t think that testing, for example, through the Internet will
be a good way to do it. It\'s more like showing that you have certain
concerns about the implications of your work that be the vigilance they
take in the French report.

PROF. SCHNEIDER: So who does this education?

DR. TEN HAVE: In most of the teaching programs we have described, the
scientist themselves, like in bioethics. Most of the bioethics programs
are taught by medical doctors, and then, of course, you have specialists
like --- well, the same for gerontology. You have specialists who are in
a particular area, but in fact every doctor has to deal with all the
patients. So every doctor should be able to teach ethics. And maybe
there are some specialists who can go in more depth.

So here there is a need also that some of the --- let\'s say, the more
experienced or more concerned scientists, they should have room to teach
ethics and to introduce ethics in mathematics and engineering and
biology and then make other younger people more interested so that there
is a kind of professionalization, maybe, in how to teach and how to do
these kinds of things.

That is what we also try to do, to make the experiences available. In
our database we now have 200 ethics teaching programs in different
countries. So if you want to start an ethics course in engineering
ethics, you can find some examples in the database.

CHAIRMAN PELLEGRINO: Dr. Dresser?

PROF. DRESSER: Thank you. I appreciated your paper. I thought it
presented a very organized, understandable review of ethical issues, and
I think your talk added to that. So thank you. I think you all are much
farther ahead in this area than we are in the US.

To me this is a similar situation to the human genome project, where at
the outset there was a realization that we\'re entering a complicated
area of science that will have ethical and socio-legal implications.
Part of the ethics work is to figure out what the issues are as well as
then to start thinking about how to work through them. So it\'s not like
cloning where we have, you know, yes or no. It\'s not that developed
yet, but you need people with ethics backgrounds to sort of think
through what are the issues and possibilities.

So much of this is anticipatory. We don\'t really know where we\'ll go.
And, again, that\'s similar to genetics, and then we\'ve seen, of
course, with stem cell research and things like gene therapy and the
artificial heart.

So we have to speculate about different outcomes and different risks and
benefits. For me one of the biggest irritants is the hype factor you
mentioned, positive hype as well as negative hype, the disaster
scenarios. So one principle that I think might be useful in thinking
about scientific responsibilities is truth telling responsibility, where
the scientific community should have as a goal in public discourse and
among themselves doing the best they can to be accurate about the
different possibilities.

I always draw an analogy to medicine, where we now think that in general
a physician should tell patients about a poor prognosis. Now, they
can\'t know exactly what will happen, but there\'s a duty to be honest
about the possibilities. And so here I would say that the same thing
holds true. And so maybe that involves debate among scientists who have
the positive views of benefits and then the more cautionary views that
can be held in a public forum, sort of a marketplace of ideas where the
public gets a sense that you don\'t necessarily want to listen to just
the positive hype. And they\'re the ones, of course, who get quoted in
the newspapers and other media. But you might get a range of opinions.

I don\'t know if you\'ve read Ray Kurzweil\'s book [The Singularity is
Near]{.underline}. There are a number of people out there writing about
nanotechnology, and I think they\'re making a lot of money from it, but
they put this very utopian spin on it, and I just think it\'s so
important for the countervailing views to come out, and I hope that the
scientific community as well as the intellectual community will speak
out with the differing views, because I think if you do have this model
of democratic control, people have to hear from speakers and writers
other than those who are promoting these ideas for their own agendas,
whether it\'s commercial or otherwise.

DR. TEN HAVE: I fully agree. Nothing to answer.

CHAIRMAN PELLEGRINO: Dr. Meilaender?

PROF. MEILAENDER: I appreciated your --- what we might call your summary
of the various issues that are getting discussion, at least in Europe,
but I\'d like to see if I could get you to move beyond that summary of
the issues. I\'d just be curious about your own normative views. You
said a number of things along the way that might provoke one to further
reflection. You talked about how there needs to be a debate about the
goals of nanotechnology, but it\'s one thing to say there needs to be a
debate; it\'s another thing to have the debate.

You talked about the possible implications for things like concept of
self and personal identity, though that\'s not supposed to sort of
divert us from other issues. You talked about a need to rethink the
ethos of research, but again it\'s one thing to talk about the need to
rethink it; it\'s another to actually rethink it.

You talked about transcending the distinction between the natural and
the artificial which, at least if applied to human beings, is certainly
a provocative thought. So what I\'m wondering is, in your own normative
views, now, not just summarizing what the European discussion has been
about, whether in this whole package of things you talked about there is
some area or some sort of concern where you think, for lack of a better
word, human dignity really is at stake, where something that significant
either in terms of something that would be a great step forward for
human dignity or something that\'s a real danger to human dignity.

I mean, is there something here that you think is important not just to
say, \"Well, people should talk about this,\" but \"Here\'s something
I\'d like to say about it\"? I mean, I\'d be curious to hear the center
of your own normative concerns on this matter.

DR. TEN HAVE: Thank you very much. Of course, I\'m speaking not as
somebody working in UNESCO, because that\'s the limitation. But I think
for me what is fascinating in nanotechnology is the possibility of what
is called in the French report the dream of the engineer, because we can
manipulate and produce new materials, and that could potentially be very
beneficial in order to have a much better use of resources, assuming
that it has no negative impact and it\'s safe. I think it will also be
very important for many developing counties. It will be a danger because
they will be out of control of their natural resources, but it can help
us to solve basic problems for humankind.

I am much more skeptical about the second area of interests, what is
called in the French report the desire to have transcendency, because
you notice at the same time and that\'s a difficulty in discussions of
nanotechnology that it\'s driven without being very clear by a kind of
transhumanistic agenda, that people want to improve humankind, not only
make better materials, but they want to improve the human being itself.

And then I\'m very critical, because who is driving this move? In what
way are we improving human beings? Because my inclination will be to
say, \"Well, in many cases human beings, they are already in a very
well-situated position. If I look in UNESCO and see all these people in
different countries, there\'s a lot to improve in their own conditions
without improving themselves. So I think that for me one of the ethical
problems is that there is continually this mix of two different motives:
the motive to improve human beings, which could be, let\'s say, having a
very negative impact on the whole idea of human dignity because it\'s
not clear how this is in any way related to the idea of human dignity.
It seems that it\'s even contrary to human dignity, because you want to
improve and make people better.

The whole debate is related to that, but there is a basic
transhumanistic agenda, and the mix with how we can improve, how we can
produce better materials for the use of human beings. So personally I am
very much in favor of trying to keep the distinction between what is
natural and artificial when it comes to human beings and trying to
overcome the distinction from the point of view of human beings between
natural and artificial when it concerns our context.

CHAIRMAN PELLEGRINO: Further questions? Leon.

DR. KASS: Thank you very much for a very clear and synoptic
presentation. I tended to listen primarily with the question in mind of
what is there in this area that is of possible interest as work for this
--- for a body such as ours. I don\'t agree with Alfonso that our task
is somehow limited in the way in which he has described it. In fact, the
statutory or in the executive order that created us --- and we\'ve
repaired to this many times the first submission, our first function, is
to conduct fundamental inquiry into the human and ethical meaning of
advances in biomedical science and technology before one gets to the
question of what are the ethical issues and before, then, one gets to
the question of how they should be resolved.

So I\'m not bothered by the fact that this is an area that doesn\'t
immediately lend itself to saying yea or nay. My difficulty comes in
trying to get a handle on what precise kinds of significance that we
face here, particularly because this is such an amorphous field. I was
trying to think of analogies. If one were to say, look, there is
something called information technology. What are the human and ethical
implications of this? Or push the clock back and say, well, there\'s
organic chemistry. We now have capacity to synthesize carbon compounds.
And one could have --- one didn\'t have such a discussion, but one could
imagine retrospectively, and that covers just, you know, from pesticides
to cures for cancer to new forms of apparel and so on.

Genetics is even more focused than this. I think Rebecca is in a way
right that this was a certain --- in this country especially when the
genetic revolution was underway, people were calling attention to this,
and the ELSI aspect of the genome project was a direct reaction to this.
But I don\'t even see with comparable clarity what the parameters are,
and maybe you could help point to a sub-area of nanotechnology that
would be suitable kind of focus substantively. That would be one
question.

And the other this is to sort of follow up on Peter\'s question, also in
a way by implication from Carl Schneider\'s question. The analytical
approach of what we need that you\'ve summarized surely gives --- is
based upon one answer to the question that scientific and technological
developments are not autonomous, that they at least yielded part that
they are a product of the human decision, and that therefore they yield
in part to what we do, and we will do better the degree to which we
understand what the issues are.

But it does seem like it has a kind of rationalist cast of its own
comparable to the science it seeks to regulate, because it looks as if
all of this could be rendered somehow manageable though a political
process if all of these things took place, and I wonder whether,
especially in the absence of a concrete sense of what actually are the
operative norms here, human dignity, as this council has discovered, is
not a unifocal thing about which all of us agree. So I wonder whether
the first question is, what is a subpiece of this such that we could
see, ah, yes, these are the kinds of ethical questions that we could
sink our teeth into; and the other is, short of this kind of global
project for what\'s necessary to govern technology in general and using
nanotechnology as the kind of latest vehicle to try to get a handle on
the juggernaut, what\'s a reasonable way to think about how ethical
reflection can contribute in a world which isn\'t really fundamentally
governed by the kind of schematism that you offer?

I mean, people don\'t simply think about these things along these lines.
Well, the second part wasn\'t clear, but maybe you could make something
of it.

DR. TEN HAVE: Concerning your first question, I\'m not sure that you can
argue that nanotechnology is raising new ethical questions. Maybe
that\'s not even a relevant --- for ethics I would say it\'s not so such
a relevant question, because in effect some people say, well, everything
we do is making footnotes to Plato. So we have new developments, and we
want to reflect on the impact of the development even if not completely
new questions are raised. But at the same time, it\'s not clear that the
framework we have developed to articulate ethical issues will apply to
this new area, because as we tried to indicate also in this report,
maybe one of the basic characteristics of nanotechnology is its
invisibility.

It is on a level that makes it absolutely impossible to control, so it
means that you cannot only wait until the products or the visibility is
there. You have to put a much higher trust in a preceding stage in
making sure that people are following some principles, which is also not
a new question, but now here we are for the first time confronted with a
technology that can be completely concealed and hidden. So I think we
have to see whether the usual approach in ethics is sufficient here, and
we don\'t know. So there is a need for more refection.

It\'s too soon to start making guidelines and legislation and whatever
because we don\'t even know what --- at the same time it\'s also clear
that if we wait --- and that\'s the experience particularly in the
European counties. If you wait too long, it\'s too late, because now we
have a chance to be on top of the developments, and that is the lesson
from genetically modified food, for example, that the ethical refection
and also another area is like in reproductive medicine --- that the
ethical reflection only started when the development was already made.

So here this is a need to bring ethics and science much more together.
That\'s one of the reasons why we often have these pleas for
interlinking science and ethics. Now, you should have scientists or you
should have an ethicist who is actually working in a nanotechnology
laboratory or center. That\'s the plea for the French ethical space in
research centers. Like anthropologists, you should bring an ethicist in
the middle of the research to identify what are the ethical reflections
that are necessary. So it also calls for a somewhat different, more
proactive, more integrated approach in the ethics of science in order to
avoid the usual complaint that ethics is always too late. Now here we
have a chance.

I think also for the policy-making community it will be important. For
the ethics community it will be important. For the science community and
also for the policy-making community because they are increasingly
worried about the impact of science in the community that you can see.
You cannot simply assume that the public will accept all these
scientific developments. If there is one, let\'s say, big scandal about
nano products, maybe the whole climate will change.

So now you have a chance. That is maybe not I am not able to say, well,
these are the main issues, but there is a kind of a general challenge
that we need maybe to transform our usual thinking about ethics a little
bit more in order to have it much more integrated with scientific
development.

The second question. Of course, you\'re right that scientific
development is not driven by ethical concerns. There are a lot of other
issues, and there are certainly limits to policy making. At the same
time, in my view, ethics has specifically the task of being idealistic
because without having an idealistic approach you\'ll be sure the
development will go in the direction that is driven by all kinds of
other concerns. So there is a need to create some kind of counterweight
to developments in terms of emphasizing values like human dignity or
autonomy or confidentiality, knowing that it will be difficult to
implement. Especially in the context of UNESCO, that is certainly the
case.

What is maybe even more important is that we have a medical debate in
our countries, like in the US and in Europe, but nowadays let\'s say
most of the publications in peer-reviewed journals in nanotechnology are
Chinese. What ethical debate is there in China? None. So there is need
from the perspective of UNESCO to say also we need not only to have an
ethical debate here to develop all kinds of guidelines in the
responsible policy here, but there is need to broaden this and to make
all counties, especially the countries where you have a lot of
development nowadays. Also concerns about the ethical impacts because
they will have the burden of irresponsible behavior first of all among
themselves. So here there is a possibility, even if scientific
development is not manageable in this respect, the possibility at least
to bring ethical concerns also on the global agenda.

I think safety is a good candidate to start because nowadays there is a
lot more concern about possible risk and safety. OECD is working on
that. Even Chinese scientists are more concerned about that now. So that
would a good starting point for making people more aware of ethical
issues.

The more fundamental question about what kind of goals are accomplished
by scientific developments in this area, they will require a debate
among countries themselves because now the agenda is driven by national
interests. But even if you are pessimistic about, let\'s say, the
effectiveness of such a debate, I think we should have a debate about
the ethical implications and the goals of scientific development in
terms of the Millennium Development Goals because all the countries have
accepted that these should be the goals for the near future.

So how can their science policies contribute at least partially to make
these goals more in reach? And if we don\'t do that, I think it will be
a very pessimistic assessment of what, as a scientific community,
internationally we can accomplish. So I think it\'s the duty of ethics
never to give up and to try, knowing that the results will be limited.
But if nobody raises the questions, they will never be discussed.

CHAIRMAN PELLEGRINO: Dr. Carson?

DR. CARSON: Thank you for that presentation. You know, back in the early
to mid 1800\'s people, the scientists of the day, thought that
everything broke down to the smallest unit, and they thought that the
smallest unit was the cell. You know, subsequently it was discovered
that there was a whole lot going on at the subcellular level, and many
areas of science have blossomed from that discovery, the whole field of
molecular biology, et cetera, with its concomitant ethical issues have
blossomed. And my question is, what percentage of the nanotechnology
advances that we\'re talking about are the result of our discovery of
things that already existed that are not really new things that have
been created versus new things that have been created?

DR. TEN HAVE: I don\'t really know the answer to that, but I think, as
argued by Schummer, it also depends on how we define our technology,
because you can bring in a lot of existing programs if you have a
definition that is only focused on a narrow skill. So there are
different ways to define and to construct nanotechnology, and that
relates also to the question of whether there are new ethical issues.
Because if you say, well, it\'s kind of a reorganization of the work
that has already been going on in chemistry, there are hardly any new
ethical issues, implying there will not be any debates on ethics
necessarily because there are no more issues. If you focus, as is
sometimes clear, on the more transhumanist agenda so that we can be
focused more on enhancement, there will be new ethical issues but not
only in relation to nanotechnology, of course. But there is a bigger
need for medical debate than in the first definition.

So I think for me the answer all depends on how you construct this
notion of nanotechnology.

CHAIRMAN PELLEGRINO: Thank you very much. We\'re right on time. We
appreciate your presentation and the questions. We will reconvene at
10:30.

(*Whereupon, the proceedings in the foregoing matter went off the record
at 10:21 a.m. and went back on the record at 10:54 a.m.)*

CHAIRMAN PELLEGRINO: Thank you for reassembling just a little bit behind
time. Thank you very much. Thank you very much. Our next speaker will be
Dr. Richard Superfine, the Bowman and Gordon Gray Professor, Department
of Physics and Astronomy, University of North Carolina here at Chapel
Hill. We welcome you and thank you very much. His topic will be a
continuation of the discussion of nanotechnology. Dr. Superfine?

DR. SUPERFINE: Thank you. First I\'d like to thank the council for
giving me the honor of speaking in front of you. And I also prefer an
informal style for the talk. When I\'m in class I get very concerned
when nobody asks questions, so I\'d actually appreciate it if you\'d ask
questions that you had as we went through the talk.

So I was very interested to see the title of my talk, and I think it\'s
a little bit broader than what I want to actually handle in my talk.
Given the expertise on this panel, for me to talk about ethics would be
kind of like reliving my Ph.D. defense, and I certainly don\'t want to
do that. So I\'m going to be sticking to the physics, a little bit of
chemistry. I understand that it\'s helpful, too, to understand some
scientific perspective of what\'s possible and a little bit about the
biological applications of these technologies and why the nano stuff is
enabling that.

So nanotechnology is --- you could generally think of it as the
proverbial nano-elephant, where everybody who grabs onto a piece of the
elephant from different sides sees something different. And that\'s in
two senses, one in which the promise of the application whether the
elephant\'s going to do wonderful things like all the work of humans or
whether it\'s going to squash us.

The other one has to do with, I think, the issue of whether right now
it\'s currently a very different thing than what we\'ve done in the past
or whether it actually bears a lot of similarities to things that have
been going on for some time. But through the accumulation of
capabilities, it became useful to give it a new name, even though there
wasn\'t suddenly a dramatic change in the actual activities that were
going on. And I think you\'ll see a little bit of both of those as I go
through here.

In my reading, what I\'ve seen about the issues that you\'re trying to
understand, one of the issues, is the pharmacological issues. And,
again, I can\'t talk about that with any expertise, but I think those
issues are real, and what I\'m going to be talking about today is going
to relate in part to some of the applications of the nanoparticles that
might have pharmacological applications that you\'ll see.

The other issue I\'m going to end up with is the issue of smaller,
faster, cheaper, and that is the issue of ubiquitous technology. And
I\'ll have a few slides at the end about devices and what I see as a
bench scientist about what is possible, what is happening in the next
ten to twenty years, and I think this could have societal and ethical
implications.

So what I\'m going to focus, though, on are, again, the properties of
the nanoparticles and nanodevices. And for the nanoparticles I\'m going
to look at their physical properties, chemical properties, and along the
way discussing each of those I\'ll talk about the biological
applications, some of the biological applications. Again, it will by no
means be exhaustive. And then I\'ll end up talking about nanodevices.

So for the physical properties I\'m going to focus on the optics and
magnetics. There are electronic properties to these materials which are
interesting. You\'ll see a little bit of that at the end when I talk
about devices. But the electronic properties largely don\'t have to do
with kind of the biological impact. And I want to talk about
specifically the mechanical properties, which is something I studied,
but, again, it doesn\'t have direct relevance, I think, to the
biological applications, though it does appear in things like
lightweight, strong materials that could affect things like prosthetics,
and it would fall in the category of the later part of the talk in terms
of faster, better, cheaper and kind of enhanced capabilities for humans
and the ethical implications that might have.

So I think you probably have seen several times in your meetings the
issue of length scale. Let me just briefly put this up here. So I\'m
focusing here now just about 100 nanometers and down. So in the scale of
100 nanometers you have the viruses. If I went up further here, you\'d
have cells out here, and somewhere around me would be a human hair. But
coming down at this scale, which is where we\'re mostly going to be, you
can see various kinds of viruses.

This is a nanoparticle. This is actually a relatively sophisticated
nanoparticle. It\'s actually a 50-nanometer nanoparticle surrounded by
13-nanometer particles. And this combination of particles with
particles, particles with molecules, is something that I\'ll end the
first part of my talk on, in something called multifunctionality, and it
is something that has a large impact and is one of the things that\'s
new about the field.

Down here at the smaller scale --- small scale is atoms --- and actually
this thing is quite old here. It looks like an abacus. It was
manipulated atoms. That\'s probably about fifteen years old out of UCLA
and IBM. And this shows the limits of the technology, where you\'re
actually using atoms for the technology.

So first I want to start with the optical properties. And so for optical
properties there are three fundamental issues in the interaction of
light with the material. There\'s scattering, which basically involves
the light hitting the particles and for the most part bouncing off or
being reemitted without change in energy or without imparting much
energy to the particles.

There\'s absorption, and this you most commonly see whether you\'re
looking through the rose-colored glasses of nanotechnology or you\'re
looking at the dark, gray future of nanotechnology. You\'re looking at
the absorbent properties of materials. And finally there\'s emission,
and so your Day-Glo sneakers that all of you are hiding in your closet.

The light is reemitted. It\'s absorbed, and then it\'s reemitted, and so
that reemission of light is something that we\'ll look at, especially
with quantum dots, and there\'s an array of quantum dots here showing
the color. And I\'ll talk a bit about that.

So first let\'s talk about waves. And this discussion here applies to
light, but also as I go through the talk later and we get to quantum
dots, you\'ll see it also applies to electrons in materials. Both
electrons and light are waves, so they have a wavelength, like a rope or
a Slinky, with an oscillation. And the light, the distance of this
between the crests here and the troughs, is called a wavelength, and
that wavelength changes as you change the frequency of the light, so it
also has a frequency. And these waves, both light and electron waves,
also have energy, and they\'re all related to each other.

And so for light here, as you look at wavelengths of visible light here,
this is around a half of a micron, and that\'s around the scale of small
cells and, yeah, basically small cells. Viruses are below the range of
visible light. So visible light is a relatively narrow range in
wavelength, and that\'s what we can see, but it also turns out that
that\'s pretty much the wavelength range where lasers can act and where
we have sensitive detectors for doing microscopy. So a lot of materials
that we\'re talking about actually emit light and absorb light in this
range.

So first the scattering of light from particles. So light is a wave.
It\'s an electric wave. It\'s also an electromagnetic wave. But if we
focus just on the electric part, it\'s an oscillating electric field,
and what electric fields do is they move charges. So a charge will move
when it feels an electric field on it, just like your static cling on
your pants will move a spark towards your pants.

And generally when you have the particle --- and this here is a gold
sphere, but it could be any particle, including a molecule. The
electrons will separate from one side to the other. And that oscillating
charge, as the electric field oscillates, makes this particle resend out
light and scatter light. And it\'s actually this phenomenon here that\'s
responsible for the blue haze or the blue sky, and it\'s because light
is scattered throughout the small particles but also molecules in the
air.

Now, something interesting happens when these particles are metallic and
when they get small, and it\'s called plasmon resonance. And so again we
apply this electric field, and the charge is separated. The positive
charges --- well, the negative charge is the electron. That\'s what
moves in materials --- will move down in the opposite direction of the
electric field. That leaves behind positive charges.

Now, there\'s two issues here. One, as the electrons move, it\'s just
like a current going through a wire. There will be some energy that\'s
lost as the electron moves, and that can cause heating of the particle,
and we\'ll talk about that in a second. The other issue, though, is when
this electron will move, it\'s kind of like having a small electric
charge over here, a negative charge, and it leaves behind a positive
charge. Those charges let themselves --- they want to pull back. So this
acts like a spring.

In other words, the electric field separates the charge, but the charges
want to go back. So it\'s like an oscillator. It\'s like a playground
swing. And if the losses in the particle from the electrons moving
through kind of like this wire are small enough, you can actually get a
resonance like what happens in a swing. And the frequency of that
resonance depends on the particle size. And you can get very strong
scattering from particles that are specifically mostly silver and gold,
so they have to be very high in conductivity. In other words, they have
to make excellent wires in order to see this effect.

Now, along the lines of a nanotechnology that\'s been in effect for
hundreds of years, stained-glass windows have actually made use of these
effects without anyone understanding at the time what those particles
were or where those properties of this beautiful glass came from.

This is from Chad Mirkin\'s lab at Northwestern. And what\'s shown here
is, as you go through a variety of particles here --- so this is silver
nanoprisms, so these are not round. These actually are kind of
triangular in shape. You go down to gold spheres. Now we\'re changing
the size of the gold spheres from 100 to 50. We go back to silver, and
now we\'re going to change the silver sphere size from 120 down to 40
nanometers. So right around here is the size of a virus. You can see the
color that\'s scattered from these particles changes. And so now by
controlling these particles and the material and the size, we can
control the color. And that\'ll have implications that I\'ll talk about
in a minute.

That\'s just scattering.

Now I want to talk about quantum dots. And to understand quantum dots,
you have to understand that in a particle here, the quantum dots are not
made from metals; they\'re made from semiconductors. And semiconductors,
like all materials, have energy levels, so they have energy that the
electrons can be in when they\'re inside the particle, and there are
energies in which the electrons cannot --- it\'s kind of like orbits in
a solar system, and you can think about where the planets are, and
there\'s nothing between them, and if you imagine for a minute that the
only possible orbits are the ones that the planets are in, you can think
of them like energy levels.

And so the electrons --- the other way of thinking about energy levels
is they\'re like rows of seats in an auditorium. They\'re there, whether
the electrons, or people, are sitting in the seats or not. And whether
the physical space in between these seats is dictated by the architect
and the material, the spacing between these seats is dictated by the
particular chemical makeup of the particle.

And so as people start moving into the auditorium, they occupy the
lowest --- the seats in the front, except if they\'re coming to my
lecture, in which case, of course, they\'re in the back. Well, let\'s
imagine I actually give a Broadway musical performance every class, and
the students are clamoring to get in the front row, and then they start
filling it up. That\'s what the electrons do. They fill up the first ---
the lowest energy levels or the closest rows.

Then in a semiconductor it turns out it\'s like there\'s a gap in the
seats, like there\'s a row here of seats which nobody can sit in. It\'s
roped off. And in many materials like metals and the semiconductors, the
electrons essentially fill up the seats up until that row before the
gap. And what\'s critical about semiconductors is this gap, and the fact
that to interact this particle with light, the electrons have to move
up.

So you can imagine if I take a person in the auditorium, and I\'m going
to move them into the row behind them, they need energy to do that. The
same thing for an electron, and this energy can come from light. It can
also come from heat or other forms of energy. And the amount of energy I
have to put in --- in other words, the wavelength of the light ---
because a couple slides ago I related the idea of energy of something to
its wavelength or color --- depends on this gap here, this energy gap.
And you can imagine somebody needing to jump across three rows of
forbidden seats would need more energy than a single row. And that
corresponds to having --- the three rows correspond to having a large
band gap, we call it.

Now, later, when the light that I\'m shining on it turns off, imagine,
this electron jumps back down, and when it jumps back down, it emits
light, and the light it emits corresponds to the energy of that band gap
again. So what\'s critical about quantum dots is that quantum dots start
changing this band gap, depending on their size. So for a large
particle, or essentially when you get to a bulk semiconductor, this band
gap is determined solely by the atoms that are in the material and their
arrangement in the material. It doesn\'t have to do with the shape of
the material. A one-millimeter chunk of silicon will have the same band
gap as a one-centimeter chunk of silicon, in fact will have the same
band gap as a chunk of silicon that\'s down to one micron.

When we start getting small, like down below 100 nanometers --- in fact,
down below 30 nanometers --- the band gap actually starts changing, and
it gets broader. I\'m sorry --- the energy levels spread out if it\'s
larger. Larger band gap means that you need more energetic photons ---
in other words, you move into the ultraviolet region of the spectrum ---
in order both to interact with this --- in other words, absorb light,
but also when this electron jumps back down and emits light, the light
that it emits --- the color it emits will also change color and will
become more bluish.

Now, to understand why size changes this band gap, you can think of kids
with a rope. By the way, you should know that in science talks I hear
all the time amongst my professional colleagues, we put up pictures like
this all the time. So you shouldn\'t feel like these pictures are being
put in simply because I feel like I\'m talking to an audience that
doesn\'t have a Ph.D. in physics. Ph.D. physicists appreciate these
pictures as well.

So here are two kids, and they\'re playing jump rope, and there\'s a
wavelength. There\'s a light there. It\'s a wavelength corresponding to
the jump rope. And this wavelength here, again, corresponds to the
energy, in this case, of the electron. In this case the wavelength here
--- we\'re thinking about inside the material is the wavelength of the
electron. Electrons are both waves and particles. The longer this wave
gets, the lower the energy is.

Now, when the particle starts getting small, these people move in, the
wavelength gets smaller. And when that happens, the energy levels spread
out, and this gap has a larger energy. So smaller wavelength means the
energy increases. Now, the reason why, as we keep moving these people
out, these don\'t get closer and closer together, is because another
effect kicks in, and that has to do with the energy levels inside the
bulk material itself. But as they get small, and these people start
getting close enough that they start approaching kind of the natural
wavelength of the electrons and material, that wavelength gets
scrunched, and the physical properties of that material generally
change.

And there\'s been a lot of research over the last ten to fifteen years
on these particles. There are several commercial companies both selling
the particles for benchtop use in the lab but also for a variety of
applications. They can be made extremely uniform, and the uniformity is
revealed in the colors and kind of the purity of colors. That\'s
directly related to how precise these are. And we know a lot of --- a
great deal about these particles, including the specific positions of
the atoms inside the particles and what their surfaces look like. And
all of that we endeavor to control, more or less, when we fabricate
these particles.

So let me turn to two applications of these particles, one that relates
to --- this one here that relates kind of to device and diagnostics, and
the second one will be a specific therapy. And in this case what we\'re
using the particles for is to detect the presence of specific strands of
DNA, which might be important for sequencing or understanding
somebody\'s genetic predispositions to disease. In this case we\'re
trying to detect a protein that might also indicate a disease that the
person might have or a specific pathology.

So there\'s kind of two approaches for this. You imagine that this
strand, that the particle here, the red one, has one strand of DNA, and
by this I mean one half of the complete double helix, so one half. And
the other color particle has a half of DNA strand as well, but it\'s
different than the one that the red particle is attached to. Then on the
surface here let\'s say I immobilize the DNA of a patient. And I want to
know what is that DNA of a patient.

I put my particles in. I know what the sequence is of the DNA that\'s
attached to the red particle, because I designed that ahead of time. I
know what the sequence is of the DNA attached to the yellow particle. My
question is what particle sticks to the surface. The one that\'s going
to stick is the one that has the strand of DNA that matches the
patient\'s strand that I\'ve already stuck on the surface. So then when
I read out what the surface looks like --- the color of the surface ---
what I\'m essentially doing is reading out their DNA sequence. That\'s
the general idea.

And you can see --- imagine here that the more colors you have available
to you, the more sophisticated your sequencing or your detection can
become, the more kinds of sequencing you can do at the same time. And
the issue here is the same if I\'m looking at proteins. You put an
antibody on the surface. You have the same antibody attached to a
particle like the blue particle. The antibodies are going to stick to
each other. But if the protein is there, the protein sticks to one
antibody, the other antibody will stick to the protein --- this is
called like a sandwich assay, for obvious reasons --- and then if your
surface turns blue, it means that particular protein is there. And,
again, the more colors you have, the more control you have over that,
the more multiplexing, in a sense, you can become with this technology.

Now, the other thing that\'s shown here, this \"MP\" means a magnetic
particle. And so what we\'re doing here is making use of the colors. So
if I can see this particle, and I see that it\'s blue or green and I see
it\'s brown, then I know that it has detected this protein and it has
immobilized the protein. I know it has immobilized a strand of DNA. I
can then take this magnetic particle, using a magnetic field, I can
separate it, and I can then take these specific chemicals from the
patient and then do other processing on them, other sensitive
processing. So it\'s both a detection technology, but it\'s also a
separation technology, again, largely for analysis.

Now, for therapy, one of the therapies that is specifically associated
with light and the optical properties is if I take these particles and I
can target them to a specific cancerous tumor. And I can do that perhaps
because I stick on this particle specific molecules that will bind to
known proteins on the cell, the cancerous cell. This particle will
target that tumor, go to that tumor and attach to it. But now I can take
that particle and I can interact with it.

If I shine light on it, like I showed previously, I can hit --- or I can
make that particle absorb light at a specific wavelength and absorb it
strongly. And what the particle does when it absorbs light, in general
it heats it up. And so now I can deliver a targeted temperature to a
tumor without necessarily focusing the laser. The laser can go through
tissue and go deeply into the patient, and it\'s only going to be
absorbed where these particles are attached to a tumor. And that\'s
called photodynamic therapy.

And this is just an example here of having cells here --- the green
cells that are alive, and the red cells that are dead here, being killed
by this photodynamic therapy, where they\'ve absorbed the particles and
then being irradiated with light. The temperature has essentially cooked
the cells.

Next, nanochemistry. So this is an issue where we ask do the particles
--- do some particles confer different --- fundamentally different
chemical effects. And the answer is both yes and no. There\'s an aspect,
first of all, to surface chemistry, which is used in catalytic
converters, it\'s used widely in the chemical industry, for performing
chemistry --- everything on airborne chemicals that are emitted by cars
to processing gasoline. That\'s called catalytic chemistry on surfaces
of metal --- metal surfaces and metal particles. So this is --- again,
this is technology that\'s been in place for decades.

But the question continues to be, when we go smaller, is there a change
in the properties of these particles. So this was an analysis done ---
an experiment done studying this issue, and what they\'ve done here is
they\'ve studied the reactivity of iron particles in getting rid of
carbon tetrachloride in groundwater. And this is kind of a complicated
plot here.

Basically these blue particles are micron-sized particles; the red
particles are nanoparticles. So there\'s really --- to sum up what\'s
seen here, this is the reactivity of the particles, and it\'s plotted on
two axes. One axis is how reactive the particles are per surface area.
Down here is the reactivity per mass of the particle. And if you
initially look at this, well, the nanoparticles are way out here.
There\'s no other particles out there. So you might think they\'re more
reactive. But they\'re more reactive per gram.

So if I have a kilogram of these nanoparticles, I\'ll get more reaction
out of them than I will a kilogram of the micron-sized particles. But
the effect in the end is surface area. If I plot the reactivity per
surface area, if I tap into the surface area particles, both the
nanoparticles and the micron particles end up at the same point on the
axis. So that means it\'s a surface area thing. I\'ve increased the
effectiveness of the particles, because everything happens at the
surface I\'ve increased the amount of surface in my chunk of material.

Now, that\'s not the full story, of course. There are --- when you look
at a particle, it\'s well known from studying the catalytic activity ---
people know in great detail the reactions that happen on specific faces
of a crystalline surface and that those reactions can differ when I\'m
on this surface here, where you can see both the gold and the green
atoms are, versus this surface here, which only displays the gold atoms.
So that\'s known.

What\'s also known is that at edges here between faces, the chemical
bonds are strained, and they\'ll actually be more reactive there, more
likely to break and cause a chemical reaction when you\'re at corners or
defects in the material. So as you go to a small particle, there\'s kind
of two things that are happening. You\'re getting more of these defects,
so they can potentially be more reactive and cause different kinds of
reaction, plus you\'re putting surfaces of different reactivity very
close to each other.

So one particle can come down to this surface, react, and then migrate
and react again with this surface. So you get more complex chemical
reactions on these particles. And that is found, but by and large I
think the field of chemical reactivity is dominated by the enhanced
reactivity due to a lot more surface area.

Now, these particles and the sophistication of the particles in
assembling them is quite amazing. Here are particle arrays. So I\'m not
looking at atoms here; I\'m looking at particles. So this here is an
array of particles --- this comes from taking a substrate and dipping it
into a solution which has lead selenide particles, which are these
larger particles here, and smaller gold particles. But they\'re in a
solution, and they start attaching to a substrate, and they form this
order array to the interactions between the gold particles, the lead
selenide particles, and the surface. See, you can form --- see this one
kind right here. Here if I make the iron oxide particles larger, I can
actually get multiple of the gold particles inside there. And if I take
triangular particles, I can get them to form these beautiful arrays.
These pictures just make me laugh when I see them, so feel free to go
ahead and laugh.

But I think this has both implications for device technologies but also
potentially again for chemistries. Again, this allows you to put
chemical sites very close to each other, where you can cause multiple
chemical reactions happening in the same place. And that\'s actually
something that biology does. Biology has molecules which have reactive
sites at different points in the same molecule. So if two reactions
happen at one place on a molecule, it means that those reactions can
interact with each other, and it\'s really one of the fundamental motifs
of biology. And here we\'re getting to this point where we can almost
start designing that with arrays of particles.

Now, individual particles can also display this complexity. These are
what are called nano bar codes. So this is a micron, so this is about 3
microns long, and you can see bands of metal here, where you change the
metal composition. So this is one particle with multiple kinds of metal
on it. This is useful, as I said, for bar codes. The reason it\'s named
for that is because, just like a bar code labels a package in a store,
you can again imagine that these bar codes can label a specific strand
of DNA that you\'re interested in analyzing.

But now taking it down to the nanometer scale --- this scale right here
is 30 nanometers. So this here, this stripe here is 30 nanometers in
size, this is about 60. This stripe here is maybe ten nanometers,
another stripe, and then this one here is maybe less than 5 nanometers.
So this kind of control can be exerted on an individual particle now.

This is a remarkable paper that came out last year out of Cal Tech. And
I think what this shows is two things. It\'s again showing the
sophistication with which materials can be manipulated, but also the
increasing game that\'s being played in using biology to allow us to
assemble materials. And so we understand enough about DNA, how to make
specific sequences of DNA and how it combines with itself, to be able to
control the three-dimensional structure that the DNA will form, based on
its sequence.

And so with this --- what Rothemund did is he sat down and in three
months wrote a computer program, and basically what he did, he said,
okay, if I have a shape that I want to create, I want my computer
program to essentially tell me the sequence of the strand of DNA that,
when put into solution, is going to, by itself, fold up into this shape.
And then subsequently over the next year or so he explored different
shapes.

Now, the program doesn\'t tell you everything. You have to go in and
tweak certain things. But this is just two of about twenty shapes that
he has in the specific paper. But you can see these shapes are
remarkable in their complexity. You may have seen smiley faces every
once in a while that are carved at a small scale by --- maybe you\'ve
seen other talks like an atomic force microscope tip that scratches
things. This is DNA. This is a strand, if you put it in a high salt
solution or heated up this strand of DNA, this would unfold and form a
long strand. You cool it back down, get rid of the salt, it\'ll condense
again, and by itself it forms this shape. You can see there\'s one over
here and, yes, some images where they\'re all over the place.

What\'s also interesting about this, that if you control the strand of
DNA, you can also control the binding sites --- in other words, places
where other stuff can latch onto the DNA. And over at Duke a former
student of ours here at UNC, Chris Dwyer, has used that to then attach
nanoparticles. We just talked about nanoparticles. Well, now he can
controllably attach these at specific sites on the origami. So if you
combine this capability of being able to control where the active sites
are in your strand, and you can control how the strand shapes itself,
you can see how you\'d gain another level of control over materials.

Next I want to turn to magnetic properties of materials and how they are
different at the nanoscale and how they are useful to us. So here\'s a
typical bar magnet. It has a north end and a south end. And it generates
a magnetic field. This magnetic field is out there in space, and it
allows the bar magnet to interact essentially with other magnetic fields
and orient it like a compass needle does. But also it affects other
magnets that come nearby.

Now, when we talk about material properties, you can actually think of
some atoms as essentially being bar magnets. So here\'s an arrangement
of these atoms inside a crystal. And you can think of it as there being
bar magnets located at the atomic positions. Typically, without a
magnetic field present, these magnets are all oriented differently with
respect to each other. It\'s disorder. And if you\'re outside the
material, you see no net additive magnetic effect. So we say the
material has no magnetization in this state here without oriented
magnets.

Now, that starts changing when I bring a magnet nearby. What happens is,
just like a compass needle, these orient --- they rotate to orient with
the magnet and become magnetized. And any material, no matter what its
size, if it has these dipoles in here, in the material, will do this.
The question becomes, when I pull my bar magnet away, my applied
magnetic field, does the material stay magnetized like a bulk piece of
iron will, or does it become demagnetized? And it turns out that that
depends on the size of the material.

So if I have a large chunk of material, the material will stay
magnetized, but it turns out that small particles, nanoparticles, become
disordered again. And the reason has to do with the fact that this
magnet here, this atom here, sees not only the external bar magnet that
I brought up that makes it orient, but it also sees the magnetic field
from neighboring magnets. This field doesn\'t just stop here. This
picture is unfortunate, because it shows --- it\'s as if the effect of
this magnet stops just a few millimeters away from this, or a few
angstroms if the case be the physical situation. But these magnetic
fields actually go throughout space.

Now, the trick in a material like iron is that these fields here are
strong enough, and the atoms are close enough together, that these
magnetic fields from neighboring atoms helps them all stay organized
once they\'ve been organized already. But you have to have enough of
these other magnets around for this one here to see enough other fields
overlapping with it to keep this one oriented.

The distance away, or how many magnets it needs to stay oriented, is a
property of the material called the block length, and the block length
is typically around 50 nanometers. So as a particle starts getting below
50 nanometers, there aren\'t enough other magnets around, other atoms
with their magnetic fields that are going to keep this oriented. And so
as the particle, when it becomes below the block length, say below 50
nanometers, it\'ll become disordered when you pull away the magnetic
field, and that can be very useful.

So here\'s one interesting property. If you take these particles here
--- this is 100 nanometers, so these are about 20 nanometers in diameter
--- when you apply a magnetic field to these particles, the particles
become like bar magnets with a north and south pole. If you\'ve played
with bar magnets, you know that bar magnets like to stick to each other
in specific ways and in fact will form chains. Well, these particles act
like bar magnets, and they will form chains. And that can be useful to
us.

First of all, we overall have changed their structure. But this could be
useful in a drug delivery application. You could actually make use of
this chain. For example, if I wanted these particles to move through the
tissue, it might be useful to have them lined up as a chain and pulling
the chain through rather than pulling the individual particles through.

And the analogy for this might be a bunch of people trying to get
through a smoke-filled room, heading to a door during a fire. If
everybody runs crazily, they\'re each finding their own way, they might
get stuck. If they\'re in a chain, following behind one person who can
see who\'s making their way through, then all of them have a much easier
way and an organized way of getting through. And in a similar way we
have hypothesized now that this might help us actually move particles
through tissue.

Now, when you shut off the magnetic field, if the particles are small
enough, the magnetic effect that binds them together will go away, and
the particles will disorder, and this chain effect will go away. And so
that\'s an effect of the nanoscale, this particular nanoscale, that we
try to take advantage of. And there\'s two aspects to this. As I
described, if I put a treatment or drug on a magnetic particle, and I
apply an external magnetic field --- this is outside the animal or the
human --- the particles are perhaps injected into the bloodstream, and
the magnetic field is applied near where the tumor is, I will draw and
collect these particles at the site of the tumor. So it\'s a mechanism
for drug delivery.

Now, once there, what do I do with it? Well, perhaps the particle, as I
said, has a drug on it that\'s now delivered. But I could go back, just
like I did with the light particles, and I can heat the particle up. And
I can do it in two ways. First of all, it might be that this particle is
not only magnetic, but maybe it\'s also absorbing light. So I combine
the properties of the particles.

But the particle by itself being magnetic means that --- and being
metallic --- means I can do an effect called inductive heating. Now,
inductive heating is a case where you apply a rapidly changing electric
field, and it drives electrons back and forth inside the metal, and it
causes a heating of the metal. This is already used to process metals in
furnaces. And essentially you do the same thing. If you put an external
coil around the person and put an alternating electric field there, you
will heat these particles up. And, again, heating up targeted particles
will kill specific cells.

Now, one thing I just alluded to which I think is a new aspect of what
we\'re trying to do is called multifunctionality. And this is a case
where we take a particle, but we want to put everything in the particle.
So maybe we want to put a sensing strategy on the particle, so we know
that it docks to specific proteins on a cancer cell, but we\'re also
going to want to attach to this particle perhaps a drug, so that when
this gets carried into the particle, it carries a drug into it. So it\'s
not only recognizing where to go but it\'s also carrying a drug in.

But maybe we want this particle also to be magnetic, so we can help it
get to the site through magnetic drug delivery, and maybe we also want
it to be optically active, so we can do photodynamic therapy. And those
four things which I described --- having a sensing molecule, having a
drug on there, having it be magnetic and optically active, has all been
done for several years on single particles. And right now what we
continue to do is to refine our capability of controlling that. But this
issue --- when we submit proposals these days, almost all proposals we
submit in the nano field for review have the word
\"multifunctionality,\" because that\'s the game.

All right, now I\'m going to turn to devices and just put a couple of
--- two cases, really, which I think address the issue of what\'s
possible with nanotechnology in the context not of therapies but
applications. So this was published earlier this year, and what this
group did --- this is Heath and Stoddard at Cal Tech --- is they took
nanowires here --- and these wires here are actually nanorods. They\'re
made of silicon. They\'re about 30 nanometers in diameter. Those rods
can both be fabricated and aligned on the substrate. So you can see
there\'s almost 30 nanometers of space between these wires. There are
literally a thousand of these wires in parallel across the device. The
device is actually in the middle here. There\'s actually two sets of
these wires. There\'s one going in this direction. Underneath there\'s a
set of wires going the perpendicular direction.

Between the two wires is a single molecular layer that has been designed
by the chemist, Frazier Stoddard. And that molecular layer acts as the
electrical connection between the two wires. Now, the electrical
connection acts like a device. It can store an electrical charge there
and act like a memory location in a memory chip. And so this chip as
it\'s been built --- it\'s not in production yet --- you\'re not going
to see it in the next five to ten years --- but it\'s over 50 times
denser than the current capabilities.

And so when you have a chip, for example, in your --- my cell phone here
has a chip in here that\'s only a couple millimeters on edge. That can
hold four gigabytes. And that\'s commercial. I mean, that\'s just
what\'s out there now. There\'s probably about 10 gigabytes in the
laboratories right now. If you multiply that 4 times 50, you have 200
gigabytes. And so the implications for having a technology which carries
an enormous amount of information in a small package --- for example,
that might be implanted in somebody --- I think is entirely possible and
something perhaps that should be considered ahead of time in terms of
the ethical implications for such enhancements in people.

The other issue is what we now call personal medicine, and every ---
about once a year or a couple times a year a big splash is made in the
scientific press about another organism whose genomic sequence has been
completely specified or improvements that are made on the genetic
sequencing of human DNA. And the common target right now is to shoot for
\$1000 for sequencing each individual person, that that\'s what it would
cost to sequence a person. And so I think there are serious implications
for when this technology becomes ubiquitous and what we do with the
information for this.

And just to give you a quick survey of some of this technology here,
this is here essentially what we call a microfluidic device. So these
channels here carry fluid. And we\'ve learned how to control the
patterning of these channels. These channels could be as small as one
micron. This one\'s actually probably about 20 microns. This is a single
cell in there. The sophistication, though --- this is one junction I\'m
showing here. Silicon wafers now are fabricated on about a 12-inch
wafer. We can cover the entire 12-inch wafer now with channels, fluidic
channels, that are on the order of several microns in size, that are
controllable with valves that can control the sequencing of fluids
moving through them.

Here we\'re controlling a cell. The cell can be lysed, opened up, and
the contents of it can be screened and moved around into different
channels, and perhaps you can move it over to a location where you do
gel electrophoresis, a common analytical technique that\'s done on the
benchtops of many labs. This has been miniaturized into a microfluidic
chip. This is the expertise of Michael Ramsey here at UNC.

And so you can do this analysis on this chip with one detection
technology. Another technology is a mechanical technology, where you
have an oscillator here sort of like a diving board. If you have a
little kid on the diving board, you get a different frequency of
oscillation than if a parent comes down on that diving board, and that
helps detect that molecules have attached to it. This one here is 100
microns in width, and I\'ll describe in a minute one that\'s much
smaller.

This is another detection technology involving again these wires that I
showed previously for the memory device, but these wires now have been
developed using single-wall carbon nanotubes, where these wires are one
nanometer in width. And the electronic sensitivity of those wires is
such that if proteins bond to this nanowire, it changes the electrical
properties, and we can address these nanowires and detect binding to
each one of them in a compact device. And this is technology that\'s
making significant progress.

This mechanical technology --- I show 100 microns here for this width
here. In my own laboratory --- as a disclaimer I should say that
essentially none of the stuff that I\'ve showed you so far has happened
in my laboratory --- but I had to get one thing in from my laboratory.
This is a --- instead of having the diving board oscillate, this is a
seesaw, which I\'m sad to say are disappearing from playgrounds, so when
I teach a class now almost nobody knows what a seesaw is. I think
everyone\'s afraid kids will get hurt.

So this is a seesaw, but it\'s twisting about --- the rubber band that
is twisting when this rotates is an individual single-wall carbon
nanotube. Again it\'s one nanometer in size. It\'s half the size of DNA.
The smallest ones we\'ve made in terms of this paddle is 300 nanometers
across. So this device here, put on top of this one here, would be a
very small fraction --- it would be about the width of the laser spot on
there.

And what we\'ve done is we\'ve succeeded in passing electrical current
through this tube, so when this twists we can detect it in an external
electrical circuit. And, again, if proteins bind to this, just like
putting lighter or heavier kids on the seesaw, you\'ll change its
oscillation frequency, this paddle will change its frequency, so it
becomes a sensing platform that becomes very small.

But the great potential for integrating this in a platform which
combines being able to sample, for example, a patient\'s blood, sense
what\'s in there, perhaps manufacture a drug and then dose it to the
patient. I talked about this being on a wafer scale, and you may not
want to have a wafer implanted in you. I wouldn\'t. But this could all
be miniaturized down to a few centimeters. And, again, the potential for
implanting such sensing devices, with a cell phone attached that would
relay real-time information back to your doctor\'s office, I don\'t see
any problem with that being an implementable technology in ten years.

I mean, it\'s amazing to see people walking around with the Bluetooth
headsets. Well, people are willing to start attaching themselves
essentially. And with the alarming things kids do these days with
attaching pieces of metal to their body, I wouldn\'t be surprised if
Mikey grows up and they want to have a Bluetooth headset attached
permanently to their ear. It would disappoint me, but it wouldn\'t
surprise me at this point.

Well, with that I\'d like to end and take questions. And what I did in
this talk was just quickly review in a very nonexhaustive way some
fundamental properties of materials at the nanoscale with some of their
applications, and I talked about what I think are quite remarkable
advances that continue to be made in the laboratories in terms of
miniaturizing, but that there might be serious implications down the
road for having these things be ubiquitous and present both on people
individually throughout society. So thank you for your attention.

CHAIRMAN PELLEGRINO: Thank you very much. We\'ve asked Dr. Janet Rowley
to initiate the discussion.

DR. ROWLEY: Well, firstly I want to thank you both for myself and I\'m
sure on behalf of the other members of the panel for the clarity of your
presentation, and I would agree with you that the relatively more simple
diagrams certainly help to explain the underlying principles. As a
biomedical scientist and somebody interested in microscopy, we\'ve used
quantum dots, and so I am fortunate to be at least in the way of a user
and somewhat knowledgeable about what they can do as compared to the
fluorescent dyes that we used to.

I think I share some of the questions and concerns that my colleagues
had at the end of Professor ten Have\'s presentation to us about the
European view and approach to the ethical issues of biotechnology, of
nanotechnology, and raising the question of what are the areas of
nanotechnology that would be most relevant for concern and analysis by
this council, because you raised a few toward the end of your talk, but
one of the implications of the field is that many of the uses are not
yet clear, and what\'s going to be used how is not yet clear.

And so as a Council on Bioethics, are we better off knowing that the
technology is there and developing and in a sense either individual
Council members or staff or someone keeping track such that if something
where we ought to be involved becomes apparent, that we\'re alert to it,
and I would agree with Professor ten Have that, as with the genetic
manipulated or genetically modified crops in Europe, nobody quite
expected the negative outcry of the public until it was almost --- it
was clearly too late to do anything about it, and we\'d like to prevent
that kind of event from happening here in the States with regard to
nanotechnology.

So we should be alert and help to educate the public on these issues,
but we\'re not quite sure --- or at least I as an individual am not
quite sure what the issues are. Now, you had the slide from Lee Hood,
and he\'s gone around, at least for scientific meetings, discussing
personalized medicine in terms of all the things you can do on a chip,
and you illustrated that and this slide of treatment of cancer cells in
the future. But the question is, is this a future that we should think
of as being sort of on our doorstep, and, secondly, what are the ethical
issues that the council should worry about? So I\'d appreciate your
discussion of that.

DR. SUPERFINE: Yeah, I apologize if the Council was expecting me to talk
about ethics.

DR. ROWLEY: No, but what are the implications?

DR. SUPERFINE: But as a bench scientist, what I see is that in terms of
therapies and drugs, there are mechanisms in place to test drug efficacy
and dangers. I\'m not familiar enough with the field to understand
whether those --- that many people are always reviewing those strategies
and wondering how we can improve those. In many cases --- in I think
most cases, when we talk about nanotechnology, we\'re talking about,
first of all, in some cases particles which are already used in drugs.
And liposomes, particles carrying drugs at the 20-nanometer scale, have
been FDA approved and used for about --- I think about five years now or
so. The actual drugs that we talk about putting on these particles are
often drugs which are already known and approved.

So I think in terms of therapy for patients, there are things in place,
and I see every reason why nanotechnology should be put under those same
guidelines. I think there are applications of nanotechnology which may
have, again, biological interactions which undergo less scrutiny than
perhaps they should, like, for example, sunscreens. It\'s considered a
cosmetic. It has nanoparticles in it. We\'ve talked about some of the
potential chemical issues that a nanoparticle can have that can be
different than a larger particle.

I\'m not aware specifically that the testing that a cosmetic goes
through is as stringent as what a drug goes through, and yet we do
deliver drugs topically with a cream put on the skin, and these
cosmetics that incorporate some of these particles being put on skin
maybe should fall under a category of drugs just because we don\'t know
really what the full implications are of these particles. We can\'t just
assume that because they have optical properties that we like and are
going to be applied outside the body, that they won\'t have biological
implications.

So I think this idea --- it actually relates in a sense to this --- we
like to design --- I talked about multifunctionality, and, of course, we
like to design that, but multifunctionality is often in the particle
already. It already has a chemical property and an optical property. And
I think maybe that that has to be appreciated as we think of what we
ordinarily would think of are benign uses of these particles.

The other thing would be in the workplace. To the extent that people are
manufacturing these particles or working with the chemicals in mixing a
sunscreen and what safeguards are in place for these people that are not
just applying it to their skin one time or a few times a day for a month
but are working with this material day in, day out, and are we properly
looking at appropriate guidelines for those people that are continually
looking at --- working with these hazards, where small effects
accumulate over time.

So that\'s what I would see in a kind of --- from a pharmacological
perspective, related to issues which I\'ve talked about here, which may
not be completely in place yet.

CHAIRMAN PELLEGRINO: Dr. Hurlbut?

DR. HURLBUT: First, I want to ask a very specific question. You
mentioned that with quantum dots the more distinct ones you had the more
things you could measure, what magnitude are you talking about? How many
distinct quantum dots can you put into a single system?

DR. SUPERFINE: Yeah. I think partially --- my guess is that in terms of
the technical challenge --- and I\'m kind of making a rough guess here
--- that in terms of the quantum dot, they may be able to differentiate
maybe 20 different ones. I think commercially you can probably buy on
this commercial sheet maybe up to 10 different ones, I think would sell
commercially, so that\'s why I\'m guessing maybe 20. But to a certain
extent that could become an information processing issue, that --- how
precisely can you determine what the wavelength of a quantum dot is.

But the other thing people are doing now --- and I kind of showed that
with what are called nano bar codes --- so it\'s one thing to take a
quantum dot, which is 20 nanometers, and how many of those can we
distinguish from each other. Life becomes a little bit easier as you
move up in scale. You can pack more information in. I\'m looking for my
slide on the bar codes that I referred to, the nano bar code. Yeah, I
can\'t seem to locate the nano bar code. But where you have stripes on a
bar code. So now, in order to see the stripes, we essentially have to
have them a little bit bigger so we can resolve the stripes.

But if we can control just literally like a bar code on a product, you
can control spacing between those lines, how wide each of those lines
are, and so for micron size --- particles may be on the order of, say,
three microns. Those rods --- they talk about getting maybe 1000
different patterns they could see. Going up in scale, there\'s a recent
paper published talking about like a 100-micron particle that would move
through a microfluidic system and can be controlled to do so, and on
there you can get --- you can actually start writing a code there
that\'s kind of like a digital code, and there you\'re talking about
millions. And so then you could use that in a separation technology or
detection technology.

DR. HURLBUT: Okay. What I really want to ask now, with that respect, is
when you showed us the manipulation of nucleic acids and smiley faces,
it struck me that you could equally as well create a sad face. And the
question is, metaphorically, what are we doing? We\'ve trying now with
several sessions to get a handle on this technology to see whether it\'s
something we should take up as a council, and if so, what are the levels
of thought about it.

And the one thing that does strike me as distinct about this --- many of
the problems are the same kind of traditional ethical issues and human
impact issues that you\'ve already reflected on, but what keeps coming
back to me is what a fundamental --- in your words, fundamental
properties, the primary properties of matter, that we\'re down at a
level of very deep control, and it seems to me that that could be not
just used for good or evil but it could be that it\'s making things more
predictable or less predictable.

And that\'s --- what I wanted to add --- your presentation is a very
unique presentation to our council, because it was more technical in a
scientific sense, but it also opened up a sense of the properties of
matter that might be at issue here. So I barely know how to frame the
question.

But is it your sense that this will be a realm of scientific
intervention --- let\'s be primarily here biomedical or body type ---
it\'s directed toward the body --- that this will be more predictable or
less predictable? And I guess what I\'m trying to ask --- I barely know
what words to use here --- but are these --- can you construct these
properties --- particles, for example --- to be more inert, or are they
less --- are the physical and chemical properties less predictable? And
we put a lot of exogenous substances into our body just by eating out at
a restaurant ---

DR. SUPERFINE: Exactly, yeah. Or McDonald\'s ---

DR. HURLBUT: --- or downtown breathing things, and we --- a lot of them
are untested, but what\'s slightly comforting about them is that
they\'re ubiquitous in nature and they\'re not so different in their
construction than what life has encountered over its billions of years
of history. But these really are different, aren\'t they?

DR. SUPERFINE: Well, yeah ---

DR. HURLBUT: Some of them, at least, are?

DR. SUPERFINE: Some --- I\'m not sure how much they\'re different when
it gets down to reactivity and interaction with biological systems and
biological proteins. I think in terms, then --- I mean, we are ---
chemistry has done a phenomenal job in drug design and being able to
tailor the positions of atoms within molecules, and to a certain extent
the limitation in developing drugs has not been so much the ability to
do the chemistry and rearrange the atoms in a molecule, but it\'s been
our understanding of what molecule we want to design. So that\'s limited
by our understanding of biology and biochemistry.

Again, there are people here I think have more experience with this
field than I do, to comment on it, but --- so I think part of it is the
limitation in our understanding of what it is that we want to design.
Now, are we going to design something which is way more toxic than ---
things that we\'ve been doing for many years --- I\'m talking about
thirty years that we\'ve been coming up with chemicals and trying to
test them or exposing ourselves randomly --- I don\'t see that what
we\'re doing is different. In the end, we\'re making molecules. And
these molecules will interact with biological systems not differently in
a sense than molecules that chemists have been making for decades.

I think one of the potential things that can happen --- and, of course,
I\'m an optimist, so I\'m going to present this in the end with some
kind of a positive slant --- is one of the things we\'re increasingly
doing is something called automated drug screening, where we want to
test thousands, millions of drugs at the same time in some kind of
automated biochemical factory, and that\'s actually work that I do as
well. And along with being able to test millions of things at the same
time, you develop libraries of molecules.

So let\'s say I have a line of cancer cells, and I want to understand
how to treat that cancer cell, and I have the ability to test a million
drugs in an hour on that cancer cell. What I have to do is I have to
develop a library of a million drugs that I want to then test against a
kidney cancer cell or a breast cancer cell and run it against all
different kinds of cells, and run it on an individual person.

So there\'s a lot of research now that goes into making libraries of
molecules, in other words, automating the process of the chemistry of
the biological molecules, in which case you\'re not designing each
molecule and it\'s being made. All you\'re concerned about is making a
million different kinds. And you may not even be concerned about what
the specific molecule is that you\'ve made, but you may have a sense
that they\'re different. You go ahead and you test them and screen them
for whether they\'re toxic or beneficial, at least within the limits of
the screening technology. You find one that kills the cell, then you
say, ah, that\'s a good one. You pull that molecule out, and now you\'re
going to figure out in detail what that molecule is, so then you can go
ahead and synthesize it in large quantities and do further tests on it
as a drug.

So what I see as perhaps different than what\'s been done in the past is
that we\'re developing the ability to generate large libraries of
different molecules in very efficient ways, whereas in the past, to
generate a new molecule might\'ve taken a benchtop scientist a year,
both with the understanding at that time but also the perspective that
you want to do one molecule at a time, know what it is, test it.

The perspective now is let\'s get a million, and let\'s test them. And
so it\'s in that sense that the game might be a little bit different
now, in the sense that we\'re generating libraries of molecules where we
don\'t know the toxicity of those molecules, but those aren\'t being
thrown at patients right away. Those are being tested, and what\'s
motivating those libraries is the idea that we can test them in
screening systems. So that\'s where my positive outlook on this comes.

The negative side might be that we\'re generating molecules that we
don\'t know what they\'re going to do. But I think the upside of that is
we\'re developing abilities to rapidly test these molecules to
understand their possible toxicity. But the game of the molecules
themselves and how they interact with biological systems, I personally
don\'t see that as fundamentally changing with what\'s happened with
nanotechnology over the last, say, ten years.

DR. HURLBUT: Just one follow-up.

CHAIRMAN PELLEGRINO: Go ahead.

DR. HURLBUT: I mean, Combinatorial chemistry and its expansive powers,
that\'s intuitive to me. What\'s not intuitive to me, and this is why
I\'m asking this question, is you take the organic type of chemicals
that --- biochemicals that have been part of the interactive life
process for all of life\'s experience for billions of years, and there
are systems for degrading those chemicals in natural biology.

Are there equivalent systems for degrading the kind of particles you\'re
creating, or are they at once less dangerous because they\'re more
inert, but at the same time more dangerous because they aren\'t
vulnerable to the degradation processes, for example, or will they
isolate in compartments within the cell or within parts of the body that
will make them dangerous?

The last session we heard about something that --- some particles that
gravitate up the olfactory nerve trap. Wasn\'t that what it was? And
that was troubling to hear that. And I\'m just trying to understand
whether this is a realm with its own distinctive dangers. And, I mean,
for example, your paper talks about the effects of interactions between
histoproteins and single-DNA molecules, magnetic effects. You\'re
talking about bringing magnetic particles into the body in a way that
they aren\'t there now.

DR. SUPERFINE: Uh-huh.

DR. HURLBUT: And will there be unpredictable --- I mean, obviously there
will be unpredictable things on some level.

DR. SUPERFINE: Yeah.

DR. HURLBUT: But do you --- I mean, you\'re a physicist, basically, as I
remember, by training.

DR. SUPERFINE: Uh-huh.

DR. HURLBUT: But you\'re interacting with a lot of biologists.

DR. SUPERFINE: Yeah.

DR. HURLBUT: And do you have some sense of whether we\'re entering a
realm of a great deal of unknown or one where there\'s more of a sense
of the known? Is it --- do you see what I\'m getting at?

DR. SUPERFINE: Yes, I do.

DR. HURLBUT: That\'s the fundamental question here, whether this is
leading us into greater darkness or greater light.

DR. SUPERFINE: As a scientist who\'s actively in this field, I\'m in the
field because I see the light. So I\'m predisposed to see that aspect of
it. But I both see the promise for controlling these materials, but I
also see the limitations in terms of both what our understanding is to
control the biochemistry of these particles, but also that it\'s really
--- it\'s been so hard to make really dramatic advances in how molecules
interact with each other in a biochemical sense or how particles
interact with each other.

So there is --- I would say there\'s some confidence among scientists
that there\'s not a huge biological explosion out there that we\'re
going to stumble on. We\'ve been at this for so long and in some ways
been frustrated for so long in understanding and controlling the thing,
that we don\'t have a sense that there is something, either from kind of
an understanding of the fundamental aspects, but also from experience,
that things are so dramatically different that the dangers we face now
are not very similar to dangers we\'ve been facing for twenty years
again, where we\'ve been inhaling particles of various kinds, and we\'ve
been using them as drug carriers in some cases, and we all along have
done some level of testing of what those particles do.

I think that caution is very warranted. So I guess I do not see from
that standpoint that the rules of the game have fundamentally changed in
what we\'re doing.

CHAIRMAN PELLEGRINO: Any other comments? Janet?

DR. ROWLEY: Could I just ask you a question in terms of followup of your
article in Science about fibrin, which was extremely interesting. Do you
see --- I\'m sure you do --- so what do you see as the application of
that kind of information? And I guess I assume that someone is trying to
make artificial ---

DR. SUPERFINE: Yes.

DR. ROWLEY: --- fibrin and use it in situations of bleeding, say surgery
or something of that ---

DR. SUPERFINE: Yes. See, that\'s an interesting question, because it\'s
also an interesting perspective on what the field is of nanotechnology
today. There is this overlap between a kind of basic science in the
sense of physics and chemistry and mathematics for the modeling and
predictability, between engineering and between biology. And so the
fibrin is actually a really interesting example of that.

We\'ve developed the nanotechnology tools to take individual fibers to
form blood clots, lay them out on a substrate, and put them on the rack,
so to speak. We can stretch them until they break. And that\'s giving us
fundamental properties about the fiber that we think are related to the
efficacy or usefulness of a blood clot.

Using --- my colleague Susan Lord is able to change the protein
structure, so we\'re going through a series now of changes in those
proteins, the fibrin proteins that make up the fiber, that she knows are
related to genetic diseases, and we\'re now testing out the fibers using
this mechanical means of stretching them to understand is there a
genetic link between the structure of the individual protein and the
fibers it makes. And that would help us understand how the fiber works.

Turns out these fibers are also --- they compete basically with silk,
spider silk, which has been a darling of materials in terms of their
strength-to-weight ratio. So if we want to make --- so a spider might
not be spinning out spider silk. He might be spinning out fibrin fibers.
And so in our laboratory we\'ve started making, by forcing fluids into
narrow capillary tubes, making fibers of fibrinogen, the same protein,
but now we\'re looking at potentially using them for other applications.

It turns out it\'s really hard to do that, and it\'s because of the
proteins. There\'s a sequence that proteins go through in the complexity
of biology and the incredible complexity of blood clotting, where the
protein undergoes various kinds of biochemical manipulation, cleaving of
various kinds, before it can start combining with itself and linking
with itself. And controlling that in a laboratory setting is very hard.

It\'s hard for two reasons. It\'s hard both technically --- to control
the chemistry to the extent we know it is very difficult, but the real
problem is that we don\'t understand the complete biochemistry of how
fibrin fibers are formed in the bloodstream. So this, undergoing ---
undertaking the technical challenge of generating materials also forces
us in a way to go back and understand the biochemistry of these fibers
and how they form very carefully and precisely. And so the goal --- the
engineering goal now forces us maybe to look at how fibers form in the
bloodstream in a way that maybe the biochemists weren\'t doing already.

And in fact one of the things we found from that study is when we form
these fibers in a slide, we actually, curiously, see sheets of ---
single-protein-layer sheets forming over large areas. And this basically
has not been appreciated before in the blood clot community. These are
forming apparently under physiological conditions in our sound chambers.
And so our initial mechanical studies now --- we may have discovered
monomolecular sheets that are forming that may also happen in the
bloodstream.

And so, again, it\'s a combination of precision physical tests that is
one of the aspects of nanotechnology, combined with the engineering
approach and the biology, is forcing us in the end to learn about and
discover new things about the biology. That\'s obviously one of the
reasons I\'m positive about the involvement of the nanotechnology with
biology.

CHAIRMAN PELLEGRINO: Dr. Kass --- and this will be the last comment.

DR. KASS: Doctor, first thank you for your wonderfully clear and
illuminating presentation. I want to underline something that --- the
implication of Bill Hurlbut\'s question and then a quick comment. I
don\'t think it\'s sufficient to say that we already have systems in
place for testing drug safety and thinking about the impact of the new
things that we put into the environment. We have mechanisms for it, but
we don\'t yet the full accounting of the consequences of some of the
things that we\'re now breathing, eating, and achieving. And there\'s a
rise in incidence of all kinds of diseases. Some people say it\'s just
better detection of hyperactivity in children, a rise of certain kinds
of cancers.

So it would seem to me that if, when we\'re following up the advice that
we got from the previous presenter, Professor ten Have, which invites
the scientists rather than to simply see the light, which I certainly
see, but the basis of their own anticipation of the likely difficulties,
to at least invite the kind of studies and maybe even to begin to do
things like, oh, what do we know about the immune system\'s ability to
deal with some of these new particles and these new kinds of things and
to do these kinds of studies in animals by anticipation because this is
novel. That would be an exhortation to you, your colleagues, and the
community, not simply to wait for others to react, to say that we don\'t
really know what this would be like, and as we\'re developing a light,
let\'s make sure that we shine the light into the possible dark places.
That\'s the comment.

The question was --- this was a kind of throwaway remark to the side in
your presentation about your disinclination to have wafers implanted in
yourself. I mean ---

DR. SUPERFINE: Twelve-inch wafers.

DR. KASS: Twelve-inch ---

DR. SUPERFINE: Twelve-inch wafers.

DR. KASS: Fair enough.

DR. KASS: Three-inch?

DR. SUPERFINE: Yeah, maybe. Three-inch wouldn\'t be bad.

DR. KASS: But basically what you\'re suggesting here is in addition to
the --- you didn\'t talk about it. In addition to the targeting of
cancer cells and drug delivery and new opportunities from sensing and, I
assume, not just sensing but delivering information. And this does seem
to be quite novel. I mean, it\'s not unprecedented because we\'re
already doing some targeted drug delivery. But with all kinds of
sensoring devices --- and I know the wired people are very excited, and
it borders on science fiction.

Are there some specific kinds of ethical questions that --- I\'m not
asking you to be an expert on them, but having thought about this, are
there things that we ought to be thinking about? Not what are the
answers, but given this new kinds of --- the ability to get information,
deliver information, not just for therapeutic purposes but for
monitoring all kinds of things. And is anybody paying attention to this?

DR. SUPERFINE: Well, if you don\'t mind, I\'m going to take that as two
questions. Your first exhortation, I think scientists do take it
seriously. And I didn\'t mean to imply that scientists are not concerned
about potential biological or environmental problems with
nanotechnology, nor did I mean to imply that the current mechanisms that
are in place are sufficient, either for what nanotechnology has coming
or what we are already dealing with. I think what I meant was that I
think what we\'re dealing with in nanotechnology is not so different
from the issues we are already struggling with, and that I think we do
have to do better.

I think as far as how the field --- by \"the field\" I mean myself, my
colleagues --- unfortunately, we don\'t get credit in an academic sense
with journal articles or funding --- in part funding --- for looking at
the dark side and studying the dark side. What drives a lot of funding
--- say 90 percent of it --- is the positive side. How are we going to
cure cancer? That\'s what our proposals are based on.

Now, increasingly NSF and NIH have appropriately started centers or
asking that parts of the shine-the-light centers are also looking in the
dark areas. And I think the bench scientists are also saying, \"Fine. We
also should be doing that. And when we do test the nanoparticle drug
delivery out on a cell or an animal, we are also going to note those
potentially harmful effects as well.\" It\'s also less of an area in
which we have expertise. This is like getting toxicologists involved
with a different kind of tool set. But increasingly those people are
getting involved within kind of nanotechnology centers. I mean, that\'s
entirely appropriate.

With regard to the second question, I think, in my view, these
technologies I\'ve talked about --- miniaturization technologies, the
smaller, faster, cheaper --- I think these things are on the way. And I
think they carry with them --- they amplify again concerns that we are
already dealing with. When we talk about computers or cell phones, we
already talk about access to technology. I mean, the ethical issue of
having a society of haves and have-nots. If suddenly I can afford to
have 200 gigabytes of memory implanted in my brain, which gives me a
library which otherwise I\'d love to have time to read, but it gives me
access to it immediately, does that confer an advantage on me over
someone else who doesn\'t --- can\'t afford it? That\'s one question:
access.

Does it change the nature of what it means to be human in a way we
should be concerned about? I think that\'s a serious thing to be
thinking about. I think the world has changed dramatically since we got
laptops, wireless, and Google. I think the access to information has
grown incredibly over the last just a few years. That\'s been a huge
change that has happened in a sense without nanotechnology, and it has
implications that we probably are not dealing with seriously.

The last part, about having everybody have their own genomic sequence on
a chip that\'s implanted in them, having personalized medicine that is
radioing through some kind of cell phone connection to a doctor\'s
office or a hospital, real-time monitoring of my health, what the dosage
level is that my automated system is pumping into my bloodstream --- I
don\'t have much of a doubt that systems like that will be available in
ten or twenty years.

The issues for that, besides have and have not and changing what it
means to be human, is how do you control the information? Is the
insurance company going to be intercepting that, or is somebody --- an
employer going to be intercepting that information? Again, I think
that\'s an issue that we\'re dealing with right now and not
understanding in many ways how to deal with it. And so I don\'t mean to
be saying that nanotechnology presents no new issues. I think it
presents very serious issues, but I think they are largely issues which
are already in front of us that we\'re struggling to deal with, and we
would do well to deal with them.

CHAIRMAN PELLEGRINO: Thank you very, very much, all of you, for your
comments. We\'ve reached that part of the program in which we usually
allow for questions from the public. We have had no official requests
for time. We are also, however, under some pressure to ask whether or
not someone who has not signed up would like to make a comment. If there
are none, we will bring our meeting to closure. I see no hands raised,
and therefore I call this meeting to closure and thank all members for
their contributions and for their words of wisdom. Thank you. And our
speaker, especially.

*(Whereupon, at 12:06 p.m. the above-entitled*

*matter concluded.)*