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Meeting Transcript
September 7, 2007

Council Members Present

Edmund Pellegrino, M.D., Chairman
Georgetown University

Floyd E. Bloom, M.D.
Scripps Research Institute

Benjamin S. Carson, Sr., M.D.
Johns Hopkins Medical Institutions

Rebecca S. Dresser, J.D.
Washington University School of Law

Daniel W. Foster, M.D.
University of Texas, Southwestern Medical School

Robert P. George, D.Phil., J.D.
Princeton University

Alfonso Gómez-Lobo, Dr.phil.
Georgetown University

William B. Hurlbut, M.D.
Stanford University

Leon R. Kass, M.D.
American Enterprise Institute

Peter A. Lawler, Ph.D.
Berry College

Gilbert C. Meilaender, Ph.D.
Valparaiso University

Janet D. Rowley, M.D., D.Sc.
University of Chicago

Diana J. Schaub, Ph.D.
Loyola College



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 and 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, [there is] 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 [to] 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, [to] make [its] objects more perfect, [i.e., the] 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 (group) published its opinion on the ethical aspects of nanotechnology 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 [one] 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 needs 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 public 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 [genetically modified] 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 [time with] 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 addressed 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 World 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 guide 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 Council 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 nano-hype, or falling victim to wild promises and letting those wild promises distort research agendas and so forth, but also nano-fear, 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 principles, 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.


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 U.S.

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. 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.


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.


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 the DNA of that 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 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 [do] 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 Caltech.  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 Stoddart at Caltech - 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, Fraser Stoddart.  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 my kids grow 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.


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.


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


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


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


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. 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 if 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 these 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.)

  - The President's Council on Bioethics -  
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