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Meeting Transcript
June 29, 2007


COUNCIL MEMBERS PRESENT


Edmund Pellegrino, M.D., Chairman
Georgetown University

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 Schoo

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

Paul McHugh, M.D.
Johns Hopkins University School of Medicine

Gilbert C. Meilaender, Ph.D.
Valparaiso University

Carl E. Schneider, J.D.
University of Michigan



INDEX

SESSION 4: NANOTECHNOLOGY: BENEFITS AND RISK

CHAIRMAN PELLEGRINO:  Thank you very much for arriving on time. Thank you. Thank you. Get comfortable and be seated. I think we've established our governmental credibility by my announcing Dan Davis' presence yesterday, so I won't do it again, except Dan is here again. Thank you, Dan. Delighted that you are. This morning, we turn to the subject of nanotechnology which the Council has touched on briefly in the past and we would like to take a look at again. Of course, quite a few years have gone by, and... see what the status of this particular new area of technology will be, particularly from the ethical point of view. 

And we've asked Andrew Maynard, the Chief Science Advisor, the Project on Emerging Nanotechnologies of the Woodrow Wilson International Center, to open the discussion. And R. Maynard, we welcome you and the podium is yours.

DR. MAYNARD: Thank you very much. Well, first of all, thank you very much for the invitation to come and speak on nanotechnology this morning. What I'd like to be able to do is to give you a really very brief overview of what nanotechnology is from a number of perspectives, what its potential benefits are, what some of the challenges are that we face if we're going to develop what I would call sustainable and safe nanotechnologies, in other words, nanotechnologies that are going to be around for more than five or 10 years that aren't either killing people or hurting the environment. 

And to do that, let me start with the definition of nanotechnology, and this is a tricky one because everybody has got their own definition, but the one that I really like is one that Professor Rick Smalley came up with and this is — let me just read this out. Rick Smalley, who got the Nobel Prize for his work on fullerines, came up with the definition of nanotechnology as the art and the science of building stuff that does stuff on a nanometer scale. 

And I like this first and foremost because it's fuzzy. It's gray. It doesn't have any sense of boundaries. And I like it as well because it emphasizes the art as well as the science. This is more than just science. But beyond that, he really hits on the three key things which make nanotechnology what it is; the building stuff, the doing stuff on the nanometer scale. 

So let's look briefly at each of those. And let's start with the nanometer scale and I'm assuming that everybody here is very familiar with what the nanoscale is. We're talking at a scale of somewhere around about one nanometer, so one billionth of a meter up to around 100 nanometers. So nanotechnology takes place in that scale which is just a little bit bigger than most atoms of molecules but smaller than the scales we see in microscale materials, bulk materials. It fills that gap where the behavior of things seems to be slightly different to what we see in individual atoms but certainly different to what we see in bulk material.

The second point, building stuff. Nanotechnology is all about having the dexterity to get down to the scale and actually do things that we couldn't do before, and let me give you two very simple examples of what I mean by building stuff to nanoscale. The first is about as simple as you can get. This is an electromicrograph of silver nanoparticles, so each of those blobs, this is a false colored picture, is a particle of silver. And you can see they vary in size from round about 100 nanometers down to something much smaller than that. 

This is in essence nanotechnology and it's nanotechnology because these particles have been made to a specific size and with a specific purpose. So at its simplest, nanotechnology is just making something very, very small which we can then do something with. But of course, we can be far more sophisticated than that. So let me give you a second example.

This is an example of what people are calling a "smart nanoparticle" and it's a particular example of a particle that's being designed to treat cancer. This is somewhat of a conceptual diagram but it is representing research which is underway at the moment. So what you have here, you have — you see the green particle in the middle. This is a nanometer sized particle. But it's been engineered to give certain functionality. 

So if you look at this, it's had a clip on the outside of it, a number of ligands which allow it to attach to specific molecules in the body. So now you've got a particle which has been engineered to the nanoscale. So if you put it in the body, you can direct it to attach either to specific cells, maybe a specific cancerous cell or specific proteins within the body.

It then has a contrast agent engineered into it, so this a particular component of the particle which allows us to track where this particle goes. So now we have an engineered particle that you can put into the body that will attach to a specific cell and we can tell when it's there.

And the third component is a sensitizer component. So now we have a particle that we can send a signal to and tell it to do something. And in this case, if we're trying to treat a cancerous cell, we can send it a signal saying, "Destroy that cell but leave everything else around it intact". So now we can see that by having this dexterity to engineer matter at its very, very fine scale, we can build very, very sophisticated structures that can do things at a level of detail that we couldn't previously do.

So that's the second aspect of Rick Smalley's definition. And the third is "building stuff that does stuff." At the end of the day, we want to use this scientific dexterity to actually achieve something, whether that's either enhancing a conventional technology or creating a brand new technology. Now, this "does stuff" can be interpreted in a number of ways. It could just mean that we can make stuff so small that we can get it into places you can't get large stuff. But it can also mean that we can actually exploit the unique physical and chemical properties of materials that we see at the nanoscale. 

So let me give you one very simple example of this and it's an example that you can find in your local drug store. Sunscreen which uses nanometer size particles of zinc oxide, let me just give you a bit of a background on this. We know what sunscreens are for. They're for protecting the skin against ultraviolet light. And one of the most effective ways of doing that is to use inorganic particles like zinc oxide, very, very good at reflecting UV light as well as visible light.

The trouble is if you take a pigment grade size particle of zinc oxide, round about three, 400 nanometers, and put it into a formulation like this, what you have created is a paint, so once you put it on you, you look white. What nanotechnology does is it enables us to shrink the size of these particles down to a specific size around about 20 nanometers or so, and something unusual happens when you hit that size. They become transparent to visible light but they remain opaque to ultraviolet light.

So now you have a product where you can actually exploit the fact that these nanoparticles do stuff at the nanoscale, so a very, very simple example, but that's in essence, what we're trying to do with nanotechnology, exploit these properties. So we have this technology and, of course, nanotechnology is bringing all those strands together so we can actually do something new. And of course, this gives us tremendous potential to do beneficial things. So let's have a look at some of those potential benefits.

And I want to go through various stages and the first stage is what this technology can do to consumers, in other words, all of us. And this is a technology I like to call an "I Wish" technology, because it's a technology where you can take almost anything that we use everyday which is maybe okay, but it doesn't work as well as we would like it to work and you maybe say, "Well, I wish, I wish my sunscreen worked better, I wish my clothes repelled stains better, I wish my iPod held more tunes." Nanotechnology is a technology which allows us to extend these conventional technologies and provide something which fulfills, well, hopefully fulfills our wishes, or most definitely doesn't in every case, but it's a technology which enables us to make conventional technologies better.

So that's one aspect of technology and if you look at consumer products which are out there on the market at the moment, we're aware of over 500 where manufacturers have claimed they're using nanotechnology to make their products better and I can guarantee there are many, many more out there where the manufacturers maybe haven't been so up front about nanotechnology, but they're still using it.

But, of course, more than consumer benefits, there are also commercial benefits here, and many are driving nanotechnology at the end of the day. If you look at the projected worth of nanotechnology enabled products over the next seven years or so, it's been projected to be worth roughly $2.6 trillion by 2014. This is the global market which are in some way based on nanotechnology. That is a huge market. And you can see why people are so excited about trying to develop and exploit this technology if they can somehow have a part of this projected market. So there are clearly commercial benefits, commercial reasons why companies, governments are trying to develop and push forward with nanotechnology.

But there are also societal benefits as well, and if you look at what nanotechnology can potentially do, there are certain things that it can do to improve the standard of our living. Let me just give you four examples. The first example is using nanotechnology to develop better materials. 

And I've got the slogan that "Light as plastic, strong as steel." What nanotechnology is enabling us to do and this is stuff which is going on at the moment, is to take conventional materials which are okay but not as good as we would like them to be, and to improve them substantially. So, for instance, you could take a light metal like magnesium which is very light but not very strong and using nanotechnology, you could put a second component in there, say a carbon based component and end up with a higher metal which is just as light as the original metal but as strong as something like stainless steel. 

And you can use combinations in various ways, but the trick of this is by using nanotechnology we can actually get down to the structure of these materials at the atomic and molecular scale to make them do things that we couldn't do conventionally. And you can begin to see the advantage of creating stronger, lighter materials, not only in energy saving, either if you're looking at cars or airplanes, but also you think about housing. Think about if you're trying to produce housing that is very quickly constructed, very easily transportable to almost any part of the world, the lighter, the stronger your materials are, the more effective you can be with that temporary housing.

A second example, energy, and we all know how important energy is these days. Nanotechnology is potentially enabling us to do two or three things with energy. First of all, it's enabling us to produce renewable energy in ways that we just couldn't do conventionally, either making renewable energy sources vastly less expensive than we have at the moment, or making them far more efficient than we can do at the moment. In fact, the picture there, you can just about see is an example of what we call imprintable electronics. These are some of the cells, where instead of using an incredibly expensive semiconductor fabrication facility, they've been printed onto a plastic substrate using a technology which is not that dissimilar from the inkjet printer you may use everyday on your desk. So imagine just having something like an inkjet printer where you can put a piece of plastic in one end and as the other end comes your photovoltaic cell or any sort of electronics. 

That is an incredible advancement on what we can do with electronics and especially with renewable energy. But nanotechnology is also increasing and improving the way we can store energy specifically with batteries. Western society at the moment is 100 percent dependent on batteries. You look at your cell phone, you look at your laptop, you look at your MP3 player, almost everything we use requires batteries, and they're not particularly good at doing what we want them to do at the moment.

Nanotechnology has the ability to significantly improve the performance of batteries both in terms of the amount of energy we can store in them and the repetity with which we can recharge batteries. So imagine, think about cars for instance, and think about a car which is solely driven by a battery, no gasoline at all. Now, imagine you have a battery which will allow you to realize the performance you can get out of a gasoline engine in terms of miles. Maybe you can drive two, 300 miles on this battery with a single charge. You can get the same sort of power and acceleration you can from gasoline. And you can recharge the battery within five or 10 minutes, which is something you couldn't do with conventional technology, you can do with nanotechnology: enable batteries.

The third example is water, water purification. And again, this is a major issue globally. How do you get clean water to every part of the global population? And it's not an easy challenge to crack. But nanotechnology again, gives us a new set of tools for being able to extend conventional technologies so we can produce clean water very efficiently, very cost effectively. 

And the final example, which I've already touched on so I won't focus on it too much, is medicine, and we're going to hear a little bit more about this later, but again, nanotechnology, because it gives us this dexterity to manipulate things at a very, very fine scale, and I should say on a scale which is comparable to biological systems and biological processes, it gives us the ability to do things in medicine that we have never been able to even conceive of doing before. 

So there are many society-based benefits or potential benefits of this technology. And then the final benefit I wanted to highlight is a scientific and a technology benefit. And I put this up here because if you look at the science community, nanotechnology is something which is really infusing and galvanizing people, giving people a purpose in their research. One of the ideas which is really stimulating people, and I'm going to come back to it at the end of my presentation, is the idea of converging approaches to using technology and converting different ideas and different technologies so you end up with an amalgam of different technologies to produce something new. And the example that I have here illustrates that very nicely. 

This is an example of a sensor which will sense incredibly small quantities of a particular protein in an environment. And you can see it's a combination of three technologies. You've got your nanotechnology. The gray tube through the middle is a carbon nanotube so this is the basis of a sensor. This is something which is a product of nanotechnology. But in that it's being incorporated into a semiconductor circuit so you have electronics technology there and then finally, the active part of the sensor is a strand of DNA which is being wrapped around the carbon nanotubes. So here you have your biotechnology. The result of those three technologies coming together creates a sensor which is capable of detecting just a few molecules of the particular analyze you're looking at and it is only possible because you've got people from three different technologies talking together and realizing when they work together they can do something new and something innovative.

So this is really a technology which, when combined with other technologies and sciences, is stimulating innovation to an extent that we haven't seen for a long time. So these are some of the benefits that we're looking at when we look at nanotechnology. But of course, there is a downside to this as there is a downside to any sort of technology where you've got benefits, where you've got something that's new, where you've got innovations, you've also got the potential to cause harm.

So I want to go on to talk a little bit about risk. And of course, what I'm talking about here is the risk of causing harm to humans, of causing harm to the environment, not necessarily the risk of losing your investment in nanotechnology. So let's have a look at this in a little bit of depth and I want to start off by underlining why we specifically ask this question about nanotechnology. 

What makes nanotechnology different to any other technology? What makes nanomaterials different to any other nanomaterials when we ask questions about possible harm, possible impact? Well, if you look at the micrographs that I've just put up on the screen, these are a beautiful set of micrographs from Professor Wang's group at Georgia Tech. And you can see straightaway that in each of those the substance that is being made has got a very, very different shape. 

You've got rings, you've got hexagons, you've got springs, you've got bizarre shapes there. And one of the things that excites people about nanotechnology is it's the shape of the materials you form which leads to their functionality. which enables them to do stuff. What is unusual about each of these micrographs is that the chemistry is the same. In each case you're looking at zinc oxide, but it's the combination of that chemistry on the form which leads to the functionality. This is where our understanding of nanotechnology departs from our understanding of chemistry, where we assume that we just need to know about the chemical identity of a material to understand its impact. 

With nanotechnology we've got an added layer of complexity where we need to try and understand the impact of shape or structure. Well, starting from that point, we can begin to explore that intellectually a little bit further and we can begin to ask the question, "Well, how might shape or structure influence the impact or the potential harm of these materials?

So we can go through a thought exercise and the thought exercise is looking at the possible impact of structure on risk and that's looking at both compositional structure, that's, in other words, where the different chemical species are, and physical structure, what the stuff looks like. And in this matrix I'm looking at the possible influence of structure on impact going from low to high, left to right and bottom to top.

If you put on here conventional materials that we deal with on a day-to-day basis such as gasses and vapors, liquids, microscale materials, generally structure doesn't play a great role in determining potential impact. Certainly, if you look at these materials, these come under what I would call "conventional understanding," where we can apply rules that we've applied for the last 50 or 100 years, and we can understand impact in terms of the chemistry of the material, its composition, and the mass of material that either a person is exposed to or the environment is exposed to. 

But you put engineered nanomaterials into this matrix and these materials that we know the function of the materials depends on structure, so it's a pretty good guess that in some cases the potential harm of these materials will also depend on structure. So we now have materials which really lie in a regime which is far away from our conventional understanding. It comes under the category of what I would call" unconventional understanding."We can no longer apply this paradigm of mass and composition to determining potential harm. 

Instead we need to look at structure related parameters, and by structure related parameters, I mean things such as the size of particles, that's — bring that up again. Got to look at the size of particles. You've got to look at their surface area. You've got to look at their surface structure and if I can go through this, this is where I really fall down using animations, because we have to spend five minutes going through them again. 

Okay, so here we've got our nanomaterials and here we've got our structure related parameters such as size, shape, surface area, surface structure, surface activity, nanostructure. In other words, we've got a different set of criteria by which in principle we'd need to assess these materials if we're going to understand what their potential impact is going to be. 

Well, that's a hypothetical thought exercise. The next question is, is there really any evidence backing this up. And the answer is, yes, there is and I'm not going to go through it but I'm just going to give you a couple of examples of what we know about the role of structure in determining the potential impact of these materials. The first example comes from a study that was carried out in the mid-`90s and this was a study where rats were exposed to a very inert material, titanium dioxide. 

This is an insoluble material which is usually used as a negative benchmark in toxicity tests and generally isn't very harmful at all. In this test, rats were exposed to airborne TIA2 particles and the response was plotted as a function of the particle matter they were exposed to. But what was interesting was two different sizes of particles were used. 

So if I first of all put up the dose response relationship for the nanoparticles, 25 nanometer diameter particles, and this is inflammatory response in the lungs of these rats, you can see the more mass that was put into the lungs of the rats, the greater the inflammation in the lungs. But then the researchers exposed a group of rats to larger particles, 250 nanometer diameter particles. Now, remember from the conventional paradigm, the chemistry is the same, the response should be the same.

But what they found was the response was lower for the larger particles. Clearly, something was happening that wasn't associated with chemistry, it was associated with the structure of the particles shown in these terms by the size of the particles. However, what was interesting from this experiment was if you replotted those data in terms of particle surface area, you found that everything lay on the same dose response relationship. In other words, when you plotted everything out in terms of a structure parameter, surface area, rather than a conventional parameter, mass, you found a similar dose response relationship. 

In other words, very clear evidence, the response was associated with the structure of the nanoscale of these materials. And there have been many other studies that have shown a similar association. Another example of unusual behavior or non-conventional behavior of the nanoscale is what happens when you expose a gang of rats to nanometer sized particles and track where these particles go. 

And in cutting form, I'm afraid, this is a study again, from the same group where they exposed lab rats to these very fine particles. Now, we know that if you expose an animal or we expose ourselves to airborne particles and those particles are relatively large, maybe larger than 2-, 300 nanometers, they'll deposit in the lungs and we know — we have a lot of information about what happens there, how they deposit, how they're cleared. But what these studies show was if you carry out the same experiments but expose these animals to nanometer-sized particles, a significant fraction of these particles don't end up in the lungs, they actually end up in the brain. 

Now, this was something completely new and was discovered a few years ago. And it seems that what happens is these very small particles, first of all, they're able to deposit in the nasal region of the rats, but because of their size, they're able to migrate up the olfactory nerve directly into the brain, essentially circumventing the blood/brain barrier. This is very clearly unconventional behavior. So we know from these studies and a number of other studies that in some cases nanoscale materials do behave in ways that we cannot predict from a conventional understanding of materials behavior.

And this presents us with quite a significant challenge. So let's start from basics again. We're interested in risk and of course, we're interested in risk because we want to be able to control that. We want to be able to reduce the impact of these technologies, these materials on people and the environment. Now if you look at this from a conventional approach to risk assessment, there are two things we need to know: We need to know something about the hazardous nature of the materials, the toxicity and health effects associated with that, but we also need to know something about exposure. We all know going back to Paraselsus that it's the dose that makes the poison, which means that we've got to know something about exposure as well as the toxicity, the hazardous nature of the materials.

Then there are a couple of other components which are important here as we begin to look at nanomaterial. The first is characterization and this is coming back to the issue that structure is important with nanomaterials. If we can't describe the materials that we're using in tests, or people are being exposed to, we cant say anything intelligent about them. We've got to be able to characterize them and characterize them appropriately.

And then of course, is the issue of outreach. If you know everything you want to know in each of those boxes, and didn't communicate that information, we also couldn't make and progress. Well, if you look at this paradigm and you ask the question, "How much do we know about engineered nanomaterials in each of those boxes", you can go through a very, very subjective exercise. And if you do that, two things become fairly apparent. The first is, we actually know more in some boxes than we do in others, so we know more about controlling exposure, we know more about toxicity than maybe we do about health effects or exposure routes. But in no cases do we have a lot of information. In other words, when we come to engineered nanomaterials, we don't have all the information we need to carry out a quantitative risk assessment. This is a major challenge because clearly these technologies are already out there. The nanomaterials are already out there. I showed you one example that many people are already being exposed to them.

How do we evaluate, assess, manage the risks if we don't know how to quantify the risks in the first place? And of course, there are a number of steps to answering this but the first step is developing the science, developing the knowledge to be able to answer those questions. We have a fairly extensive list of questions which desperately need answering. We need to get on and answer those. 

And I put this out because this was the result of the deliberations of a number on international scientists last year that got together to ask what are the big challenges here that we need to address if we're going to move forward with understanding potential risks and what is the time scale over which we need to address those questions. And we came up with what we call "five grand challenges," and these five challenges didn't cover everything that we need to know about addressing the risk of nanomaterials but really gave a fairly robust framework within which we can make progress. 

So the things that we identified are: we need to know how to measure exposure to these materials. This seems pretty basic but we're still struggling to work out how you actually work out how much of these materials somebody is being exposed to or how much of these materials is being released out into the environment. 

We need to know how to carry out toxicity screening tests. Again, fairly fundamental but something that we haven't got agreement on at the moment; if you're producing a new material for the market, how to evaluate whether it's safe or whether it's harmful. Thirdly, we've got to beyond that though. Because there are going to be many, many more new materials and products coming out, far more than we can possibly evaluate on a case by case basis, we've got to have predictive capabilities. We've got to have the science which allows us to say if somebody creates a new and esoteric material, what is the likely impact of that material so we can make judgment calls before it's too late, before that material has entered the environment and possibly caused harm.

Fourthly, we need to develop a life cycle approach, a life cycle mentality to assessing the impact of these technologies and materials. It's no use just being focused on one particular area whether you're looking at the workplace, whether you're looking at the environment, whether you're looking at disposal. You've got to integrate everything together. So if somebody is going to generate a new material or develop a new technology, we've got to be able to assess what its potential impact on our lives are going to be right from the point at which it's developed in the lab to when it's produced to when it's transported, to when it's put into a product to when consumers or people use it, to when it's eventually disposed of in the environment. If we can't take that holistic approach, we're going to miss things.

And the fifth challenge, the first four challenges were to the scientific community. The fifth challenge was actually to the people that support that science community. And that challenge was to develop strategic research programs that are going to enable us to do the rest of the work, the other four challenges. 

So that gives an idea of the risk challenges that we face and what needs to be done if we're really going to get a good handle on managing these risks. But, of course, there's another side to this as well. There's the side, the response side. How are people that are going to be using these technologies, how are people that are going to be impacted by these technologies going to respond to the technologies? So I want to spend just a couple of minutes looking at that. And this is the response of potential users and potential beneficiaries. And we know, of course, from experience over the last 50 to 100 years, that science and technology really are social functions. You cannot isolate the science from society, and now I'm preaching to the converted here with this particular group, but it's something that the science community is really only just beginning to wake up to and realize. But it's very clear, we've got to understand this dynamic between science and society. 

I put this up because this is one of the earlier protests against nanotechnology. It happened a few years ago and it demonstrates that there is this tension between the people that were developing these technologies for and what they think of the technologies. This is a demonstration outside Eddie Bauer and it was — these people were demonstrating against the use of nanotechnology to create stain resistant fabrics. In fact, they were actually demonstrating against the use of this technology on pants but it's the same technology as you see on something like this tie. It's a technology here they put a nanometer scale or a nanometer thick layer of a particular substance on the fabric so the fabric feels like a natural fabric, silk in this case, but it repels stains very, very effectively. This particular demonstration failed for two reasons. The first reason was, everybody can remember that these were topless people demonstrating against something. They remember the topless thing but they don't remember what they were demonstrating against or why they were doing it. 

The other problem with the demonstration was if you look at sales of Eddie Bauer clothing, nanotech clothing, it actually went up after this. Most people saw the demonstration. They didn't know what it was about but they heard this idea that you could buy stain resistant clothing, so they went out to try it. But it does demonstrate that the people are beginning to become activated against nanotechnology, asking questions about whether they really want it in their lives. 

We can take a little bit more of a formal look at how people are responding to this technology and these are the results of an attitude poll that we undertook last year which tried to, among other things, get an idea of both what people think about nanotechnology, how they're responding to it. And in this particular part of the poll, we asked the people who were questioned whether they thought the benefits of nanotechnology would outweigh the risks, whether the risks outweigh the benefits, and we were asking this question before we told them anything about nanotechnology, and we told them something about nanotechnology and asked the question again.

So here are the initial impressions. This always amuses me because in this poll something like 30 percent, in fact, it was more than 30 percent of the people asked knew absolutely nothing about nanotechnology but they still had an opinion about whether it was good or bad. And of course, this reflects other surveys like this, that people are quite ready to make an opinion whether they have information or not on which to base that opinion. But we saw that when people were originally initially asked about whether benefits would outweigh risks or vice versa, there were actually quite a lot of undecided people, 43 percent or so weren't sure. But out of the rest, the feeling was generally that the risks were likely to outweigh the benefits. People were somewhat cautious, as they are with any new technology.

We then told the people who were being interviewed, a little bit about nanotechnology. We stressed the benefits, but we also said there are some unknowns about the potential impact of this technology, and we asked them the question again, afterwards, do you think the risks will outweigh the benefits or vice versa. And, of course, we found that the undecideds, most of them decided to make a decision, but the group that grew the most was the group that thought the risks would outweigh the benefits. And this was very interesting because it demonstrated that even though we stressed the potential benefits of this technology, people were cautious about accepting a technology into their lives which might imply some risk to them, some risk to the environment.

Consumers, people in society, are naturally cautious about technologies. And of course, this is important as we push forward to develop this nanotechnology. We try and realize this promise of $2.6 trillion worth of products, of goods. If the people that we're supposedly developing these for don't want them, we've got a disconnect there. And then finally, because this is a group that deals with ethics, I thought I had to say something about ethics. And I need to say here very, very plainly and clearly, formally, I know nothing about ethics. I'm speaking here as a complete novice. But I thought it was useful to say something about this because ethics and nanotechnology is something which has been discussed quite a lot over the last few years. It's something that you now have academic institutions set up to address. So I think it's something which certainly is appearing within the dialogue and something that does need to be addressed. 

But as I look at this, I struggle with this probably because I know nothing about ethics, but if you look at nanotechnology, more than anything nanotechnology is a tool kit. It's a way of working with different types of technology, different types of science to extend them, to enhance them. So to my very simplistic mind, talking about the ethics of nanotechnology, is the same as talking about the ethics of a hammer or the ethics of a wrench. It makes little sense in isolation. Where it does seem to make sense to me though, is talking about the ethics of how you use the technology, what its impact, what its potential impact might be. And as you begin to ask questions like that, it becomes much more interesting and one of the areas where it becomes particularly interesting is seeing how nanotechnology can be used to enhance, to augment, other technologies. 

So if you go to the final slide, we know we're surrounded by many different types of technology. Obviously, you've got the biotechnology, which has really grabbed the headlines over the last decade or so. But you've also got information technology which is really steaming ahead with computers getting faster and smaller all the time. The way that we process information getting more and more sophisticated all the time. And then you've got what is normally referred to as cognitive science. I put cognitive technology up here, the idea of understanding both how we think, how we make decisions, and influencing or augmenting that.

What is interesting about nanotechnology is that it crosses over and augments each of those specific areas of technology. So you can see in each of those areas, if you take biotechnology, nanotechnology provides a took kit where you can actually do the things in nanotech you would like to do but previously you couldn't do because we didn't have this dexterity to work at the molecular level. If you look at information technology, nanotechnology gives us the ability to extend our information processing and storage capabilities to an extent that we couldn't do using conventional technologies. 

If you look at cognitive science or cognitive technology, nanotechnology now gives us the took kit to further understand thought processes in a way that we couldn't previously do. You're looking at the science of how we actually use our brains, how the brain functions. It also gives us the ability to actually augment the cognitive process, providing external input to that process in a way that we couldn't do using conventional technologies. So nanotechnology, as a tool kit, extends these technologies and, of course, then the question is, "What are going to be the implications, specifically the ethical implications, of those extensions of these technologies?"

But nanotechnology is something else as well. Nanotechnology forms a bridge between these technologies. So instead of biotechnology going its own way, information technology going its own way, cognitive technology going it's own way, we now have cross-talk between them and we have a merging of the technologies, and of course, this is what people talk about when they talk about convergence. A convergence is a — somewhat of a controversial subject to talk about but what is very, very certain is that we're now living in an age where you are having this mix and match between different technologies and that mixing and matching is allowing us to do things which would be inconceivable five, 10, 15 years or so ago. And it's this convergence which really does challenge us as we develop new abilities, new ways of doing things, new ways of thinking and that really, I think is where some of the big ethical issues come. What happens when two people get together and have a synergistic relationship where they produce something which is far greater than the sum of the parts? How do we deal with the consequences of that?

Well, let me just finish by pulling out three key points from everything that I've said, and I've covered quite a lot of ground in the time I've been speaking. The first point is, I've talked a lot about the risks and the benefits of nanotechnology but I would contend at the end of the day an important question to ask is, "Can we afford not to develop nanotechnology?" If you look at the potential benefits that it offers, would we be wrong to stifle this technology and not realize those benefits? 

The second point, is that if we truly want to develop nanotechnology into something that's sustainable, and by that I mean something that's going to be around for a few years, we need smart science. We need science that understands the context within which it is carried out and the context within which that science is transferred into technologies and into products. And that means conversations not only between the scientists, but also the scientists and the ethicists, the scientists and the people that are eventually going to use these technologies and benefit from them. 

And then finally and very critically, nanotechnology without foresight will lead to a crisis, and this seems like common sense. But it's common sense which doesn't seem to translate into policy in many cases. You can think, if you're looking forward to the nanotechnology future, we're on a road and that road is going to have bends in it. If we're driving blind, if we're ignorant to where those bends are, we're going to pass straight into them, we're going to have a wreck. The only way we're going to be able to navigate into a nanotechnology future where we actually see the benefits succeed and we minimize the risks is by having the foresight to see where those bends are going to be and working out how to navigate round those bends together. By together I mean, the policymakers, the scientists, the consumers, other stakeholders working together towards a nanotechnology future. Thank you.

(Applause)

CHAIRMAN PELLEGRINO:  Thank you very much, Dr. Maynard, for clear, concise presentation of a complicated topic. We will open up the discussion now for the members of the Council who may have questions or comments. Before I do that, Dr. Hurlbut will be opening the discussion for the Council as the first member.

DR. HURLBUT: Well, I was assigned the task of trying to set the frame for the discussion but I have to admit, I find this a very challenging assignment because in spite of the fact that I've now been at several meetings on nanotechnology, a couple in Europe in which there was an international conversation, one in Phoenix and one at the Woodrow Wilson Center and so forth, I still find this a very, very difficult subject to get a handle on, an intuitive feeling for and therefore, to frame the larger issues, not just of risk, but of the broader bioethical considerations. 

And I'm keeping a file of innovations in this field and I'm on several listservs that send these around. And I'm more or less astonished about every three days by something that's tangibly not just speculatively, but tangibly accomplished. And I don't know whether it's my background of training that leaves me incapable of grasping the subject or whether it's just the nature of the subject itself. I'm trained as a physician. I think in kind of organic chemistry and this seems to have qualities, unintuitive qualities for me of physical properties, a combination of biological, chemical and physical properties that don't fit into the kind of interactions that I understand. And it worries me that maybe my body doesn't understand these either, not just my mind. 

That maybe the encounter with these innovative material productions might contain a lot of unexpected results. Now, you've touched on that in a quite compelling and I think quite, well, let's say frightening way. I mean, the idea that something is going to migrate up my olfactory nerve into my brain, really, that's scary. But it's deeper than that because it seems to me that if you look at it logically, the history of life close to four billion years by all physical evidence, has evolved to adapt to a certain set of chemical and physical parameters. It's both used this and also protected against the adverse possibilities of these. And our whole body is finely tuned to the natural chemistry of our environment and the natural physical forces of our environment. 

In fact, the very word "human" as has been noted in this Council before, the very word "human" comes from the same Latin word as "humus," earth or soil. We are creatures of the earth, adapated to and through and with the nature of the earth. These particles being produced by nanotechnology have a troubling unnaturalness to me, and therefore, an unintuitive character in assessing their risks or their potential engagements with the natural realities of our body.

The interlocking complementarity of our natural process could be deeply disturbed by these. Now, there's obviously a lot of hype and a lot of fear associated with this. The promises are beginning to almost sound like the promises of the stem cell technology. Not that I think that those will not produce potentially at least very, very interesting advances and I'm very excited by this science and not all a nay sayer even while suggesting some caution in our assessment and our promises.

And I think we could get overly afraid of this technology and that would be tragic given the number of self-evident tragedies or challenges that need to be addressed. We're in this technological cycle where we need to solve our problems with additional technologies, which create more problems and maybe the nanotechnology or the convergent technologies can do this. But I also worry a little bit about the nature of the opportunity. It seems to me, and this is a funny way to say it, but at this level there is no "dirt." 

There's nothing between the molecules. There's nothing that interferes or stabilizes or renders awkward this technology. It's, if I understand it right, an operation at the most fundamental levels of physical forces, and that means that as has been said, we're controlling the properties and behavior of matter at the smallest scale and it's been called "domesticating atoms." Well, what does it mean to domesticate? Domestication sounds like such a benign word, but what it will amount to is what you said very plainly when you showed us that slide that said "I wish, I wish, I wish", and that raises the question of shaping nature at its most fundamental levels and its more basic powers to our desires, our images and ideals. 

This has been called an "enabling technology," and it clearly is going to the bottom of the powers of matter, fundamental forces of nature to serve that which our human nature thinks nature ought to be, including revisions, potential revisions of human nature. So [there] the risks are self-evident and obviously, on the radar. There might be some subtle ideological questions or more fundamental bioethical concerns.

Now, when it comes to the risks, they converge in a strange way with these agendas or these concerns. Obviously, something that's unnaturally durable, nondegradable, that concentrates in compartments of the body, has subtle unpredictable effects, is very worrisome. And I would add to what you said, a worry that's been on my mind recently as I've gotten to know this field a little bit, it's known now that cell differentiation during development is not just what you might call that soft interaction of biological parts or chemical forces but that actual physical forces shape the differentiation of cells and tissues.

So, for example, mesenchymal stem cells given a short platform of adhesion, will form — round up and form an adipocyte, a fat cell. Given a broader, flatter foundation or platform, they will form an osteoblast, the foundation for bone production. So it's a physical force. It's not exactly a chemical force in its foundation. So just to raise one thing that I've not heard said, this could — just imagine what this could do if some of these particles ended up in certain compartments of embryonic development, even in relatively small concentrations. The subtle effects of — teratogenetic effects, deforming effect of natural development could go largely unnoticed and have strangely powerful effects if not obvious deformities, maybe shaping human development in unpredicted ways. 

But to move on from those obvious concerns, what does it mean to have power to manipulate, to mimic, to invade, to monitor, to enhance, to override, to improve of focus, hyperspecialize, what are we to make of these statements about cyborgs, endowing human beings with new capacities, new properties, reshaping human destiny? I really don't know to get back to the way I started this, I don't know what's realistic about all that. But I do think it raises some questions that go beyond what we've previously thought of in bioethics. 

At first I thought, well, this is really all about risk, but I'm increasingly realizing that nanotechnology delivers new powers that really are quite different than those that we assessed for example, in our "Beyond Therapy" report, not that they aren't in the same ideological categories of concern but that they require some focus of consideration beyond what we've already done. 

I think the possibilities are fantastic in both the positive and negative meaning of that word but I — and I see that this is a global phenomenon that there's obviously a great deal of research on this in — all over the world. Asia is very involved actively and the commercial implications are huge, you said I think it was 2.6 trillion. I guess that's the price of the full products produced, so it's a little bit misleading. The nanotechnology component of that is just one, right? I mean, if you have a computer that's a non-tech enhanced item, that's the whole cost of the computer.

DR. MAYNARD: It's the whole cost, yes.

DR. HURLBUT: Okay, but still what's the difference? I mean, the fact is it's very fundamental and will drive commercial realities. So obviously, there are going to be very big, vested interests in this that we'll have to be monitoring to make sure that the interest don't outweigh consciously or unconsciously the concerns on this. 

And finally, since it is so global and so fundamental, I think we should have our radar up and be attentive to those people who are speaking in futuristic terms about trans-humanist, post-humanist, and as I said, cyborgs and transformations of humanity. We should be attentive to this. These are species questions, not national questions. We need to have an international discussion on this, and I think our fundamental starting point to return to where I started, would be a concern for and appreciation of the unnaturalness of this technology and the, if not perfect by every human desire, the awesome reality of our natural functioning that we should stand before with humility and acknowledge both its fragile frame as the foundation for our freedom, our sense of meaning and human purpose.

So I think there's a lot here. Well, that's enough.

CHAIRMAN PELLEGRINO:  Thank you very much, Bill. 

DR. MAYNARD: I actually found those comments incredibly stimulating. Despite your reservations, I thank you. It's actually sparked off a number of thoughts that I hadn't previously had in this area, so it's a very useful start to the discussion. A couple of things I would like to say in response to that. One of the problems we face with nanotechnology is that things are just not black and white. It isn't a case of nano is unnatural, other things are natural. 

And the best example of that is the fact that we're all exposed to nanometer-sized particles all of the time. As we're sitting around this table, we're all breathing in probably between thousands of millions of nanoparticles and these come from vehicles. They come from fires. They come from sea spray, a number of sources. So as we've evolved, our bodies have evolved clearly to deal with these particles. But the thing that I find interesting from your comments is you talked about unnatural things in the body. And of course, there's a difference between the natural nanoparticles or the nanoparticles our bodies are used to, and what we can potentially do with nanotechnology which is create very esoteric, very unnatural materials and particles. And perhaps this is where we need to make the distinction as we try and grapple with this gray area between what maybe is important and what isn't important, asking the question what can we do that the body really has not had any exposure to, that we haven't been able to evolve the defenses against? I think that was a very insightful point to make.

The other thing that I thought was really very good was — very useful was focusing on what happens at the molecular level within the body. You mentioned cell differentiation, for instance and the role of physical factors in that. And I think we're just beginning to realize how significant nanoparticles in particular are, or nanostructured surfaces, in determining biological functions. And this is a fairly new area of research, but the more we look into it, the more we realize that we can have some very significant, potentially some very damaging interactions on that level and I think we've got to adjust our mindset and think what happens at the biological level, which, of course, is on the same scale as many of the nanomaterials we're forming.

Looking to the future, of course, a lot of the debate over nanotechnology and potential impacts started off looking at very futuristic ideas such as self-replicating, nanobox, nanomachines, the idea of trans-humanism being able to so augment the human conditions that you produce something new. And it's very hard to tell yet whether these are purely science fiction or whether there is some reality to those ideas. And the nanobox almost definitely is science fiction, but the idea of being able to augment humans, people, to the extent that you actually really transcend the current species, there is possible a lot of potential in there and certainly a lot of people thinking very seriously about it. Whether that will be a very real issue over the next decade or so, I think is unclear but certainly, if you're taking the long-term view, 50 years plus from now, I think seeing how people are really desperately trying to apply nanotechnology in this area will likely to have some fairly significant challenges there.

And one final thought from your comments, part of the problem, part of the grayness in this discussion is the fact that we're trying to discuss things under this term "nanotechnology," which really isn't very helpful. And I'm sure at some point, as we continue in this debate, we need to move away from talking about nanotechnology and talk about the specific applications, because as soon as you get into a specific technology or a specific merging of our ability to work at the nanoscale with other technologies, you've got something concrete to discuss and something concrete to evaluate in terms of whether it's a good thing or a bad thing or how to develop it responsibly.

CHAIRMAN PELLEGRINO:  Thank you very much. Members of the Council? Dr. Foster.

DR. FOSTER: I was supposed to say something later but I'm just going to go ahead and say something I might have said later. I think that — I thought that was a very helpful statement that Bill made, but there's nothing that we do that is not associated with harm. You know, in medicine we have this thing, "First do no harm." Well, you know, if you take an aspirin, a baby aspirin a day, you cut your colon cancer 50 percent, and you cut your heart attacks dramatically and you probably cut dementia, you know, Alzheimer, dementia but you may bleed to death because you take that.

And if you thought the "Physicians Desk Reference," as far as I know there's no drug that does not have a series of negative things, interactions. There's nothing that I know without — you know, without potential harm. So the question — and the question of harm always comes up when something new develops. I mean, you get — you develop the first vaccine and you know, you're playing God, you know. And you have all of these worries about certainly, my goodness, nuclear power, we've been through this.

So the initial anxieties, because it's unknown, are very hard to come by. And I think, I'm really going to come to ask a specific question in just a second, but it's going to be very hard to find out what's going on here. I mean, you have mentioned in the — about the five great challenges and so forth, that you want to try to do in vitro studies and those are great for doing the effects of particles and so forth, about how they might kill cells.

But in terms of humans, it takes years and years of clinical studies to find out

— I mean, for years and years we thought estrogens were good for women, you know. Then that changes. I mean, for years we thought tamoxifen in breast cancer is good. Well, it lasts for five years and then it switches. So these are very long studies. I noticed some of the things that you mentioned are 10 years and 15 years. It's not going to be easy to find out what is going to happen here in humans and that's what you have to do.

The pathways are known. The olfactory bulb, you know, there's a big argument about whether in humans pheromones exist. You know, in animals it tells you, you know, you get sexually attracted and, you know, if you've got a male phenotype if flies then you usually reject the male flies in terms and things like that. So we've known for a long time that things go to the olfactory bulb and go up to the brain and so forth. 

The difference is we've got a particle that normally might go into the lungs, it's small enough to do it. So I think that trying to find out what happens is going to be hard, but what we have to do in medicine and everything else is to sort of calculate a health benefit ratio. Let me just pose a question. Let's suppose it's possible to make clean water everywhere, okay? Most people think that the leading cause of death in the world in undeveloped — is dirty water, okay, not malaria, close but it's dirty water.

And let's suppose that we find out with prolonged studies that nanoparticles might have the capacity to induce cancer in you know, one in 10,000 people or 10 in 10,000 people or maybe deform an embryo. The question is, if you — if you save 3 million lives a year from clean water, whatever it is, I don't know what that number is, is that worth the risk for a few people having — now, that's a serious question, to say where you know that there's harm, but the harm is tiny relative to the calculus of the benefits. 

Now, I think that Bill would probably say, well, no, it's not worth that risk, you're manipulating. I don't know, but those are the sort of serious questions I think we have to deal with. 

Now, the finite question I want to ask is, what do we know — Bill used the term that these things are going to stay around forever, that they're immortal. I want to know, do we know anything much about half-lives of these things? What is the carbon chain? You've talked about this mimicking asbestos, you know, and so if we cut the size of this, we might not get it into the — you know, what do we know about natural degradation or half-life about a constructed — I'm sure it depends on the thing that you construct but do we know anything about how this disappears or does it? Is it eternal?

DR. MAYNARD: Okay, thank you. Let me just deal with the risk issue first and I'll talk about the half-life and how long these things last. The risk issue is, obviously, part of a broad ratio. How do you deal with risk in a society where things seem to be very polarized in the risk rate and people assume that you can make something safe when, of course, you can't. And the associated question there is who makes the decisions? Who decides that the benefits outweigh the risks with a particular application? And those are tough issues which I don't think are unique — well, they're not unique to nanotechnology. They cross the board and I don't think we have any good solutions here within society but they're issues which need to be addressed exactly the same way they need to be addressed with nanotechnology, especially this issue of who makes the decisions as to whether something is good or whether something is bad?

And we're seeing a shift there with the civil society groups may be taking a larger role than they have in the past with science and with technology and being the decision influences or decision takers. Now, that may not be a good thing, but if it's happening, it's something that needs to be dealt with. So I'm not going to provide any solutions but I'm going to agree with you, this is a really major issue that we need to tackle with and tackle.

The big question about half-life and persistence, the answer is that we don't know in many cases but it's a question that's got to be asked of very, very specific nanomaterials and nanotechnologies because it's going to be different depending on the type of material or type of technology or type of application. In some cases, saying you're producing zinc oxide particles such as the ones in that sunscreen there. We know enough about their solubility to be able to estimate how long they're going to last and they won't last forever. They'll eventually either dissolve or become incorporated into other matrices. 

If you're looking at something like a carbon nanotube, I don't think anybody's got a clear idea of what their persistence is and how long they continue to play an active role in any system that they're a part of. And that is clearly one area of research that's got to be addressed because if we're developing a legacy that we're going to have to deal with over the next few decades, we've obviously got a serious issue to face up to. So, yeah, the answer is there isn't an answer yet.

CHAIRMAN PELLEGRINO:  Dr. Meilaender?

PROF. MEILAENDER: Thanks very much for explaining to me a little bit about what I don't understand here. I was interested especially in something that Bill picked up on in his comment, your use of the "I Wish" formula because it raises a different kind of question from the "risk of harm" question. Serious as that question is, I at least know how to think about it, kind of. I mean, we're accustomed — we may not have good ways of thinking about it, but we're accustomed to thinking about benefits over against risks and you know, if I could have a stain resistant tie, and could actually eat spaghetti in public how good this would be, but when you start talking about sort of augmenting the cognitive process, there could be risks of harm connected with that, but of course, it's not just a question of risk of harm there. And I guess what I'd like is some help in knowing how to think about that.

In other words, if we're just worried about some possible harms, we can kind of try to assess them and decide whether it's wise to go forward or not. But if we have a technology that we've done that with and we think it's at least relatively safe and wise to go forward with, but that has a whole range of uses, some of which just give me the stain resistant tie that would be a great boon and some of which augment the cognitive process, and if we're maybe inclined to think that a stain resistant tie is a good thing, but augmenting the cognitive process is troubling, how do we sort of slice through that and proceed on the one front and not on the other? I mean, I don't expect you to solve that question but I'd like to hear you talk about it.

DR. MAYNARD: I think this is partly why I say that you've got to look at the applications rather than just the technology in a generic sense because if you talk about the technology in a generic sense, you end up with these apparent possible conflicts which are very hard to resolve; whereas, if you have something specific, you can have an intelligent conversation.

So, for instance, if it looks like a particular application of nanotechnology or a convergence between nanotechnology and something else is going to lead to a capability to sufficiently change or augment cognitive processes using that example, which are going to challenge the way we perceive ourselves or do things at the moment, then you can take fairly clear action, or you can really have an informed discussion about whether this is a good thing or a bad thing or where it needs to be steered.

If you're looking at a generic technology which might make ties stain resistant but also conceivably following a certain chain of events, might also lead to cognitive augmentation, you haven't got anything sufficiently concrete to grasp that you can have an informed discussion about. So at the end of the day, I think we've got to have mechanisms in place where we can have these discussions and dialogues and make decisions, but we've got to be focused on the specific applications and get away from the discussions of nanotechnology into the discussion of what specific technologies can be developed and applied, if that makes sense.

I'm not sure whether I've skirted around the question or whether I just haven't answered it.

CHAIRMAN PELLEGRINO:  Professor George?

PROF. GEORGE: Thank you. I'm really following up, Dr. Maynard, on Professor Meilaender's question here. I'm just trying to think how to organize our worrying along a time frame. When should we worry about what? So this is really just a request for a clarification. I gather that for the short term, by short term I mean sort of now to five, 10 years out, you're saying all we need worry about is the safety of using nanotechnology for ends that almost everybody would agree are desirable and not ethically problematic. That where we are as far as the technology itself is concerned, those are what the risks are, perhaps, an additional risk of being exposed to naked hippies when you go to try to buy a winter coat or a kayak. But then the longer term, I gather, is when we would face questions about the possibility of this technology being used for ends which themselves would be at least ethically questionable, where you would have a dispute breaking out among reasonable people of goodwill about whether that's a good thing to do. Have I got that right?

DR. MAYNARD: I think you have, but I need to qualify it, and I need to say that I talk from a fairly specific perspective. My background is in trying to understand risk of harm to people's health. So, of course, that's the perspective I bring to this debate. It doesn't necessarily mean that some of these broader long-term issues are less important. It's just that I am — I'm biased in my views. But as I try and step back, I think what you say is broadly correct.

As I see things and again, thinking of nanotechnology simply as a tool, something which isn't good or bad in itself, the first line must be to tackle these fairly immediate questions of what is the potential to cause harm to people, cause harm to the environment, how can we either avoid that or minimize it or move forward responsibly?

And it's very hard to see any of these broader ethical issue really sort of hitting the ground in a big way over the next sort of two to three years. At the same time, clearly these issues are coming along. As we get increasingly sophisticated with nanotechnology we are going to be able to do things that we couldn't conceive of doing at the moment. And we've at least got to start the thought process. We've got to have mechanisms in place where we can actually understand the framework within which we can discuss these issues and try and make informed decisions. And I don't think we can start too early in that process because these are going to be really complex issues we face, and if we don't have the framework within which to carry out those discussions, we're going to be caught out in the cold.

PROF. GEORGE: Well, from a policy vantage point, would you say that it's likely not possible to put into place at least on a cautionary basis, legal restraints on ethically problematic uses of the technology without putting restraints on the technology itself?

DR. MAYNARD: In principle, yes, but again, I think you've got to have a specific way of using nanotechnology to talk about. I don't think you can talk about it in general terms and put those constraints on nanotechnology in general terms. 

CHAIRMAN PELLEGRINO:  Dr. Carson?

DR. CARSON: Thank you for that fascinating talk. It really stimulates a lot of thoughts about potential benefits that this could bring about. You know, I could see ways of enhancing nutrition or maybe preventing the uptake of unwanted things in the diet, but for everything that's good, unfortunately people have a way of making it into something bad. And I'm just wondering, you know, particularly in terms of the sensitizers, what would — or is there anything that would prevent al Qaeda terrorists people from maybe putting something in the water supply that would sensitize people to sunlight and drive everybody underground or something like that? I mean, I know it sounds like science fiction but are those possibilities and is there any safeguard?

DR. MAYNARD: In terms of the possibilities, they're frightening. I can guarantee if you get a group of a half a dozen nanotech researchers in a room and ask them what is the worst thing you could do with this technology, they would come up with things that would give you nightmares. It's very easy to think along those lines. So, yes, there is the potential to do really quite a lot of bad there. It's not discussed significantly within the community, though I am sure that various agencies are actually looking at those sort of applications. So, could a terrorist group, could another country use nanotechnology for bad? Most certainly.

Are there any ways of controlling that? It's very, very hard to see how. And the reason I say that is that even though a lot of aspects in nanotechnology are very sophisticated, there are aspects of it where you can potentially do a lot of harm with what I would call "garage science," stuff that you can do really very simply as long as you've got the imagination and a modicum of intelligence and knowledge to do that. So it's one of these things which I think is going to be very hard to control from the top down.

Now, I suspect that there are other ways of dealing with issues like that. And again, I don't think this is something which is specific to nanotechnology. It's going to be across the board with how we develop and use science and technology in general. But I suspect that there are innovative solutions to trying to minimize the bad use of it without coming down heavy-handed and say, "We're going to ban this particular type of research". 

CHAIRMAN PELLEGRINO:  Dr. Kass.

DR. KASS: Mr. Maynard, thank you very much. It was very, very helpful. I'm leaving aside the larger questions that were raised by Meilaender, George and Bill Hurlbut and trying to say at the level of risk about which you were speaking. I'm still somewhat perplexed and here's my difficulty. In the presentation when you spoke about potential risk, the main insight was that we are in a realm of unconventional understanding because besides mass and composition, we have all these other parameters to consider. And yet, you didn't then, it seems to me spell out more vividly the kinds of risks that those different parameters raise. That would be the first point.

Then you go onto to say, "Look, the real risks, the real assessment to benefit and risk can't be dealt with by nanotechnology in general, but you have to think about the various uses and how it's connected with biotechnology, information technology." So okay, so I have to then start thinking about the specific areas where these things are going to be applied apart from what might simply be loose in the atmosphere or wind up in the water as a result of the unintended consequences of going down this road.

But then finally, in the kind of summation, you go back to this notion of nanotechnology as a whole. Nanotechnology without foresight is going to lead to crisis, and I'm afraid I don't have a clue as to what kind of crisis you want me to be thinking about as we start to drive down this road. I appreciate very much that you were giving us an optic task here and for this ignoramus you've done it splendidly, but I would wonder if you could take up those — help us understand just in terms of the level of kinds risks you want to concentrate on, how we should understand this particular concatenation of comments that you've made.

DR. MAYNARD: Certainly, and thanks for giving me the chance to clarify that. You're right, I skipped over an awful lot in the interest of time and brevity. The specific risks, at the moment, I would probably talk about uncertainty rather than risks, in that with a lot of these materials we're just uncertain whether they're going to impact on people and the environment or not. But if you look at the research, there are a number of behaviors that are being seen which you don't see with larger structures and large materials. So I mention the fact that in the lungs of rats and these very find particles of chemically inert material, elicit a much greater response for the same mass of material when there's smaller particles. That's fairly basic stuff and that's been repeated a number of times.

We've also seen that the surface chemistry of these materials is important as well, so if you put a material into the lungs which is comprised of small particles, but it's also got a very active surface chemistry something like crystalline quartz, the smaller the particles the greater the response for a given mass of material. So again, that's a structure related issue. We've seen as well fairly recently, there are indications that very small particles can interact on a biological level in fairly unique ways. There's been some modeling done which indicates that if you have carbon 60 molecules, which are a little over a nanometer in diameter, in principle if they come into contact with DNA, they could actually change the structure of DNA by fitting specific counts within the DNA structure. 

We've also seen some research recently that suggests that nanoparticles can effect the fibrillation of amyloid proteins and obviously, potentially leading onto diseases such as Alzheimer's disease, Parkinson's disease. This is very early research. It's only been done in vitro but they've seen with particularly amyloid protein that if you expose it to these various types of nanoparticles, you can significantly enhance the onset of fibrillation. So it's an indicator there that you're seeing something happening which seems to be associated with the size, the structure of the particles.

And these are just indicative of a number of studies which tell us that certainly in the body, and we've seen this in the environment as well, that nanostructure materials, nanosized particles, do have different impacts at a biological level than larger structured materials. Now, the question which hasn't been addressed is what are the consequences of that. Okay, that tells us something about the potential hazard but in terms of the risk, we don't know enough to know how that's going to effect disease, how it's going to effect the environment. So there's this huge area of uncertainty there, and that's really what needs to be addressed if we're going to get a clear understanding of things.

Now, in terms of crises, I use that term very, very generally and it covers crises of disease and environmental impact, what happens if we develop a technology or a material which has a long-term impact, something like asbestos and we don't spot it early enough? How are we going to deal with the crisis that that leaves us with? I'm also thinking in terms of economic crisis. If you think of governments and industry investing huge amounts of money in this area, governments in particular, governments are investing now in technology for wealth creation, for job creation. If something goes wrong with it, that investment is going to be lost. That's another type of crisis.

And of course, the third crisis is what if we don't realize the societal benefits of nanotechnology? What if we get something wrong early on because we're stupid, because we don't engage stakeholders in the right way, and so somehow people reject the technology wholesale and prevent us from developing the good that it can do. So that's another type of crisis. So those are the sort of things that I was trying to get at with that statement and you're right, I use — even though I decry the term nanotechnology, I do use it incessantly and so there is a bit of a dichotomy there. 

CHAIRMAN PELLEGRINO:  Profession Schneider?

PROF. SCHNEIDER: That was really cool and I was very pleased to be able to understand everything that you said, I think. But one thing I didn't understand was the exchange that you just had which you said first, that it was really very hard to discuss any of these kinds of ethical problems and practical risks in the abstract or in generalities. That makes a lot of sense to me. 

But you also said we needed to have mechanisms in place for discussing these kinds of problems and I didn't understand what sorts of mechanisms you had in mind for discussing things that we cannot yet identify.

DR. MAYNARD: I'm not 100 percent convinced that I know myself. The thing that I was, I think, trying to convey is it's structures and organizations that are able to respond to challenges fairly rapidly and that would include groups such as this where you actually have people able to get together and explore really quite complex tricky issues, provide good information and guidance on how to address them. It also includes structures such as maybe sort of government inter-agency groups, organizations, that can somehow track developing technologies and respond fairly rapidly to the challenges that they seem to be presenting. It's really putting structures in place so as challenges come up, we can respond intelligently putting structures in place so you can initiate dialogues between different stakeholders effectively and move towards making decisions. 

PROF. SCHNEIDER: We already have lots of kinds of technologies and lots of kinds of risks. Do we not already have those kinds agencies, the kinds you're talking about that are already in place?

DR. MAYNARD: No, I don't think we do and the reason I say I don't think we do is that nanotechnology and the promises and the possible threats have been known about for a good 10, 15 years now and yet here we are still struggling with the most basic questions. And there's been no evidence that we had the structures and the groups in place that are able to take leadership on those issues. 

CHAIRMAN PELLEGRINO:  Dr. McHugh?

DR. McHUGH: Well, like everyone else, I very much enjoyed your presentation, Dr. Maynard. And I have a fairly simple-minded question that comes up as I listen to you. You could probably answer it and dismiss it. After all the issue of size, shape and structure as important elements has been a part of functional biochemistry really for a half a century now, the structure, helical structure, double helical structure of DNA, after all is an issue of shape and structure to carry out its functions and receptor structure is, as you showed, and lock and key pharmacology is, I presume at the same level of discourse that you're carrying out here.

And I'd like to hear just a minute [about] how our basic understanding is being — I see the applications and I agree with you and I agree with Dan Foster that it's in the applications that various kinds of risks and benefits will occur, that we need to study in themselves, but much would be illuminated if we had a better understanding of the structure of life at the nano level. And issues — for example, the important and very fundamental biological issue of protein folding and the way it functions and how it's so unpredictable.

Will more studies — are more studies of this sort at that level going forward that would ultimately allow us to better understand just how risks — what risks are based on other than simply the epidemiology of risk and the fear that novelty brings to us? It's a simple-minded question.

DR. MAYNARD: No, actually it's a very important question and the answer is, yes. It actually touches on an issue that I feel very passionately about and that is trying to combine knowledge and understanding across different scientific disciplines to address these issues. You see that with the development of nanotechnology applications and our basic understanding of what happens at the nanoscale. 

You don't see it so much in terms of trying to understand those biological interactions. But, of course, it's essential. As you said, if you look at biochemistry, we understand a lot about structure and form at the nanoscale and biological systems and there's knowledge there which we can actually apply to the nanotech world to try and understand what's happening at that level. 

Likewise, if you're trying to understand biological interactions of nanoscale materials with biological molecules, we have a wealth of information in material science which is only just being applied to the biological sciences and again there is a synergy there which I think can be applied rather than reinventing the wheel. In terms of whether research is going on looking at interactions of the biological level, yes, it is, not enough though.

If you look at — a number of groups, a number of people, including myself, have tried to take a critical look and a fairly analytical look at what research needs to be done if we're going to understand what the potential impacts in nanotechnology are and to work around those potential impacts. And the research really sort of falls into two counts and of course, you have continuum between them. You've got very targeted research which needs to be addressed in the short term, looking at the very specific questions people are asking, such as, if I'm producing a nanoscale powder, what happens if I breathe it in my lungs? What sort of respirator do I use to stop myself breathing it in, what sort of control measures do I apply? Those are pretty immediate questions which require answers, but in the long term, if we're truly going to make progress, we've got to understand the basic science of what's happening and that's where you get to the research into biological interactions.

And so we're now beginning to — people are beginning to propose having a two-pronged approach looking at the very targeted research and the more exploratory research. And if you look at an agency such as NIH, they're beginning to develop exactly that model, trying to work out how you can understand the basic biochemistry of these interactions and then begin to work from that basis to understanding how you can predict behavior and maybe modify behavior.

CHAIRMAN PELLEGRINO:  Thank you very much, Dr. Maynard, for a very, very illuminating discussion and presentation.

We will now have a break for 15 minutes, return at 10:15.

(A brief recess was taken 10:00 a.m.)

(On the record at 10:16 a.m.)

SESSION 5: NANOTECHNOLOGY, MEDICINE, AND ETHICS

CHAIRMAN PELLEGRINO:  Will the Council members be seated. We'll wait a minute or two. Thank you. We return. Our speaker is Professor Mauro Ferrari who is Professor at the Brown Institute of Molecular Medicine and Chairman of the Department of Biomedical Engineering at the University of Texas Health Sciences Center at Houston. He also a Professor of Experimental Therapeutics at the University of Texas MD Anderson Cancer Center. Professor Ferrari.

PROF. FERRARI: Good morning everybody. I am a practicing nanotechnologist and I come in peace. 

(Laughter)

I find that the nanotechnology is the ultimate team sport on a number of different levels. On the scientific level because as you've heard with the very eloquent presentation that Dr. Maynard made, it brings together people from different disciplines and they are all required to make a functioning gadget that can solve a problem of interest. So in that sense, it is a team sport. It is also to me a great beauty of nanotechnology is in the fact that at the nanoscale, distinctions between academic fields which are, of course, by and large, human artifacts, that stand in the way of progress more than helping progress in my mind, those distinctions disappear and there is no biology, chemistry, mathematics, engineering. It's all pretty much the same. It's a bunch of items and work some way and we try to find a way to use these items and the way they work to solve problems of interest to the community.

But I also find, and again, here I find the dialogue of Dr. Maynard's perspectives and this will be probably the last time I do, because for the rest of the talk there's going to be a number of disagreements, which I think is healthy. So the other aspect that is really central for nanotechnology is that in order to be able to reap the full benefits of what nanotech can do for the community we need to work as a team, the scientists, but most importantly the stakeholders, the community in all of its aspects and with that in mind, I am profoundly honored and very, very grateful to have received an invitation to address you today and I'm really thankful for taking the time and picking up this issue. Dr. Pellegrino, thanks so much for the invite.

Now, when it comes to building teams, I find that a very important component of team building is for the potential team members to have the courage to show up in front of one another and declare their weaknesses. If you do that, building a team — I was in sports for a number of years, not with any consequence, but at least I know the philosophy. If you are able to declare your weaknesses to one another, that's how a team comes together. 

So in walking the walk after talking the talk, what I thought that I would [talk about] here is something that I'm terrified about. I've come here not to give you my regular lectures, I give many of those on nanotechnology and this medical application or the other medical application; cancer, heart disease, diabetes, whatever, we have many programs in my lab. But I thought I would come here and talk about something for which I have no academic credentials whatsoever, and that is bioethics. And I'm doing that in the hope that I will be of service to you, that will help at least understand the poor and incomplete perceptions that I personally have of the ethics world and that perhaps other members of the nanotechnology community share with me.

So let's start from the beginning. I have had the privilege of working with Dr. Smalley and to take his advice, especially when I was in service to the National Cancer Institute where we put together the world's largest program in nanotechnology applied to medicine that issued the year 2005, still remains the world's largest program. It was a great exercise, just the assembling of that, and I had the privilege of leading in that proposition. I was brought there for my academic role, part time to do that. It turned out to be one of the situations where you end up working 700 percent of your time if you put all the pieces together. So it was a great privilege. The best part of that was the fact that it gave me the opportunity to interact with a great number of wonderful people, very smart, very competent, very provocative, very different opinions, all the way from the Nobel laureates in medicine and biology to the Nobel laureates like Dick Smalley in chemistry to community leaders, community advocates, naked hippies and all sorts of different — great CEOs so that give us so we could actually refine a prospective that then could go out to the community and be embraced. And we have one representative of that theme here with us today. That would be Dr. Travis Harris who is now with the White House. He's sitting back there.

And I think that was a very successful exercise thanks to the work of Travis and others. So having spent some time with Rick, I think some of his philosophy clearly permeated through our thinking. When I was asked to provide the definition of nanotechnology for Nature Nanotech, the three pieces that I put in somehow echo as I realized for the first time today his definition of stuff doing stuff and being small, essentially the three components that I use again as my personal definition. I'm not arguing that it is better than anybody else's but that's what I go by.

Number one, you have to have a full device or as key fundamental crucial component of a device that has to be nanoscale in dimensions, 100 nanometer, 300, 500, I don't particularly care about being too specific on that. Second, the device has to be man-made, otherwise it's biologies, chemistry, we have all sorts of other disciplines that account for things that are small and everything is made of atoms and molecules anyways. That doesn't mean that nanotech is all of science, even though some are trying to kind of argue that.

Third, because of the smallness or that nanoscale nature of your device or the crucial component of your device, you have to have the property that you would not observe for the same thing at the microscale. Let's call that a new property or an emerging property and that can be chemical, physical, biological, whatever it may be, combination thereof.

So far I would think that most people in the nanoworld kind of agree, plus take or give a little bit with this definition. I add a fourth component that is a guiding principle of a lot of the work that we do in our lab, which is that you have to have a mechanistic explanation, a cause and effect type of explanation of what your new behavior is, why it takes place in a certain way, and usually the language in which his mechanistic understanding has to be expressed is the language of mathematics. 

So we kind of use the shorthand expression, "It ain't nano if you don't have the math to back it up," which is of course, a shorthand. It's an Italian slang, spaghetti western style, but I think it gets the point and the point is that unfortunately, a lot of what we call nanotechnology today is really observational science. It's taking pictures and describing them more than it is — which is a prerequisite first step towards doing a real nanoscale science which requires that understanding.

Well, nano, the best function in nanoscale devices anywhere in the universe, I think nobody would disagree that in biology, the dimensional realm between the 10 and the 100 nanometers, we have large biological molecules that do an absolute spectacular diversity of complex tasks. We are moving all the way into the domain where viruses live, which are also machinery of incredible complexity and the spectacular ability to multiple different functions. So now the fact that we are even talking about nanotech comes from the fact that at least I mentioned scales, now to have arrived to different techniques, it is possible to make human artifacts and control them and use them and assemble them. We've just scratched the surface but I think that is why we are here today.

Now, I will also make the comment that of the words I don't like nanotechnology is probably number one and one, I think, the great scourge that we have in nanotechnology is that the word was invented in the domain of science fiction and we continue to carry that connotation with us as we are doing science and as Nobel prizes are won pertaining to the domain of nanotechnology, several. So we continue to carry somehow in the back of our minds this notion of nanotechnology as that nanorobots so the nanogadgets, they really have no citizenship whatsoever in the field of science and have been proven to be impossible on solid scientific grounds. 

The nanosubmarines, that nanoboats that you see illustrated in covers of magazines and permeating discussions. Even today we saw some of that among this most learned group. They really have no citizenship in science whatsoever. They are, if you will, a consequence of the fact that the word nanotech originated in the domain of science fiction. 

So we all need to be cognizant of that as we filter out of the back of our mind some of these things that perhaps belong in Hollywood movies but they are certainly not what nanotech is operationally in the trenches, in the — for instance, in the clinic. So that we don't have the misunderstanding — of course I'm not blaming anybody for that. It's just a statement as to how the field has evolved and how, and of course, how certain words have a staying power and certain concepts have a staying power in everybody's mind is a natural development.

So I identified, again, these are my personal taxonomy, at least three classes of nanotechnologies. I will make quick reference to these three classes with a few examples and then from this slide on, I will just give you my chicken scratches of what my understanding of bioethical concerns are for you to correct me and to start a conversation.

So first, perhaps the most famous nanotechnological implements in medicine are nanoscale particles, particles on the order of say 10 to maybe 500 or perhaps even 1,000 nanometers for injection in the circulation so that they can deliver drugs or they can deliver imaging contrast agents selectively to sites of interest, to sites which are diseased, for instance. Think of a cancer lesion or a cancer metastateses. We call these things generally nanovectors and Dr. Maynard gave a very eloquent summary of some of the multiple functionalities that are built into these so let me not go over that again.

But I do want to say that I wouldn't want you to think of nanovectors as an object of the far future or even of an object that will come into play in the near future. We have had manmade nanoparticles not only research laboratories for 20 years plus but in the clinic for 10 years plus. Anybody that goes to a cancer clinic this day for say breast cancer, for ovarian cancer, certainly for Kaposi's sarcoma, as of two weeks ago for multiple myeloma, among the options that are offered is the option of treatment with liposoma (phonetic) formulations of otherwise very toxic drugs such as doxorubicin that carries tremendous cardio toxicity so if you package doxorubicin inside of a liposoma which is a little fat globule that mimics the essentials of a cell, of a biological cell, as a container, you put doxorubicin inside of that, you inject that in the general circulation, somehow these particles find their way to concentrate preferentially more in the tumor than they do in healthy tissue, and the reason for that is that the blood vessels of the tumor are leakier, they have little openings, little gaps, that these particles, if they are the right size, can penetrate whereas they cannot penetrate in other parts of the body. This is a very rough first order explanation but perhaps serves to make the point that these drugs have been in the clinic and they are actually front-line therapy for many different cancer types or different situations that arise in the continuation of the development of cancer for recurrent disease for metastatic disease, been with us 10 years already.

There is a second class of nanoparticles that has recently made quite a splash, quite an impact in the fight against breast cancer. It is a nanoparticle formulation of taxol and we're not going to use the trade name for that, but it is something that has really made a tremendous impact in the fight against breast cancer, especially recurrent and metastatic disease. There is a large number of nanoparticles that are being researched in many laboratories, mine is one of those, that are in different stages of the preclinical development pipeline and many of them are approaching or are already under consideration by the Food and Drug Administration. I an thankful that Dr. Sanhei (phonetic) is here from the FDA, that is a leading figure in FDA's involvement in nanotechnology. 

So these nanoparticles, that's a big part of the story. I will come back to them and I will discuss some of the things that we can hope to do with those. And some of these, you heard the famous names, is the of course, the lipizones, the quantum dose, the nanotubes, and there's many other different types, biologically derived nanoparticles, many different types. I think of the order of five to 10,000 different nanoparticle types being researched worldwide.

Second class implants that have nanocomponents. These are things that could be put under the skin or inside of the body to perform different functions. Let me give you a few examples of that, and these are really objects that are more near future or perhaps farther future than available right now. On the sensing side, you can imagine having sensors built, put under the skin that pick up simple physical variables such as acceleration, shock. The sensor could be used in a number of different context or perhaps temperature differences so you can respond to extreme emergent conditions. Or perhaps the sensors — the next generation of sensors that people are thinking about would be sensors of biological molecules, so molecules of biological significance, glucose for diabetes or certain narcotics that have to do, perhaps with cancer or with cardiovascular disease. Well, the notion of building sensors that can be implanted in the body and give reliable information about molecular concentrations in the body, that is a long-term proposition. There are technical hurdles even though this has been researched for many years, there are technical hurdles that make that very difficult, but physical sensors can be implanted. Pressure sensor, you know, flow sensors, that can be implanted and actually an ideal compliment for implants that we already put in the body everyday such as implants of course, of pacemakers, of stimulatory implants for cardiovascular function.

Another class of implants that may very well benefit from nanotechnology is that has to do with cell transplantations. Sometimes we think, and this thought has been going on historically for about 50 years, that it should be possible to use cell lines derived from animals to supplement diseased functions in a body and again, take diabetes for a moment, the islets of Langerhans inside of somebody's pancreas that produce insulin, if you could replace those with cells that come, for instance, from animals, wouldn't that be great? It would be self-regulating in their release of insulin. They would be essentially bringing back health, bringing back homeostasis. 

Now, the problem with that is that as you transplant the cells across different species, or across different individuals, but even more across different species, there is a very strong rejection response. Now what nanotechnology can help do is keep the molecules that govern this rejection response outside from being in contact with the transplant itself. So the potential notion there would be that of regenerating, if you would, that's a form of pretty elaborate tissue engineering, if you will, essentially reconstructing a distributive pancreas, if you will, or at least the endocrine part of that, the part that releases insulin when the glucose level triggers that release.

Now, what are ethical issues with that? Well, one is of course, the notion of is it ethically acceptable to use animal parts into humans? Of course, we use animal derived products in medicine and we have for many years. Insulin is a great example, porcine, pig derived insulin was always the mainstay until of course, we developed the recombinant DNA approach to obtain an insulin. There are many other examples of that. So it is not an ethical issue that is very novel. It is perhaps, made more intense by the fact that nanotechnology can help do things that perhaps, in order of magnitude, is more complex so it is intensified in its magnitude, but it's not enough of a concern. And if I can give you a sneak preview, I frankly, don't think that with nanotech we have no ethical concerns. I think we have increased, of course, the necessity to address some of the concerns that are pervasive throughout medicine but with my very limited understanding and ability, I cannot thing of truly novel concerns.

The third and then I promise that I will — oh, well, there's another example of implants that you may be interested in, implants for neuro-stimulation in the brain, for instance to give sight to the blind. And that is something that has been worked on, again, also for many years. That includes the use of probes that stimulate selectively certain parts of the brain so that you can get a signal that corresponds to a visual stimulation when necessary. That is something that really requires very specific stimulation that I think, by necessity, if it ever comes to bear, it would be through a nanotechnological device. Other type of stimulations for muscles, for wasted muscles, for muscles that are no longer capable of performing their functions. That is also something that can probably be done with something larger than nanotech, but in the same ballpark type of developments.

Will it be possible to ever develop brain implants that allow us to think faster, to think better, to make better decisions? That's sci-fi. For me that's sci-fi. There may be other people and I will stand corrected if I see a scientist that makes a good argument. Best I can do to you is speak my conscience. I don't believe that stuff. 

Next, laboratory devices and here is where nanotech is probably going to make a tremendous impact, already is very soon and the ethical issues with that I'm interested in discussing. Devices that we have in the lab that we don't put inside of people, that we don't inject, that we don't — that don't go up our nose into our brains, stuff that we keep in the laboratory, in the desk and that we use for processing biological samples so that we can find out as early as possible if somebody's got cancer or not, heart disease or not, so that we can intervene promptly with the best tool ever developed, for instance against cancer, and that will not be a magic drug. That will be the knife. If you catch cancer soon enough, today we have the tools to cure all of it by and large, and that is called the knife. So the notion of nanotech on the prevention and the screening side, I think that's something that we need to focus on.

Okay, and then let me show you again, let me show up naked here in my weaknesses and tell you, I've taken medical ethics in medical school and that's as far as I went and I actually participated and still do, in the medical board of institutions and sometimes I'm involved in discussions that have to do with ethical considerations and the life decisions and whatever, and I will say that I've been benefitted immensely from the works that came from this group and I thank you very much for them.

So my recollection from medical school, the way I was taught, and again, I'm not advocating this over any other framework, just telling you where I come from, as captured in my accent if you will. So my accent is I understand beneficence [as] "do most good," that's easy. I understand the non-maleficence, I think that means, "first do no harm," and I never learned to pronounce the word maleficence, and probably spell it, but you know what I mean. 

Number three, "respect," now what is respect? I understand respect. Again, I'm just telling you this so you can factor out my — the poverty of my understanding from my statements. "Autonomy," people make their own decisions as much as possible. We need to enhance the ability of people to make their own decisions. Self-determination, human nature and it was mentioned earlier and thanks for reminding us, that "human" and "humus" have the same root. The other word that's got the same root in my mind is "humor," which somehow I find that humans have this self-ironic nature to our existence. 

Human nature, going beyond human nature, I think is a question of respect for species and for all of us as members of the species, that would be my personal perspective. To meet the aspect of justice that I really want to focus on a little bit today, is that to have equal access. Okay, so considerations on beneficence, what good can medical nanotechnology do? I have made — already I've given you a few examples but just to make sure that we place the considerations in context, I work mostly in cancer and I have the privilege of working at the MD Anderson Cancer Center, which is a great medical center and the volume of cases that we see is absolutely unbelievable. I think it's the largest in the country by a factor of 10 or something like that. And so I'm reminded daily, even though I'm not a clinician, of the fact that one person every four minutes dies of cancer in the United States. Maybe I got the wrong — one person a minute dies of cancer in the United States, four persons a minute in Europe, 20 worldwide. So if you do the numbers, every week to 10 days the cancer casualties in the United States equal or exceed the casualties due to say 9/ll plus the war in Iraq. I think these are type of considerations that need to give us pause as we try to find a balance between the benefit, as was said earlier on, between the benefit and the risks that we embrace, of course, by bringing up different types of technologies and approaches.

So in my mind and I've already spilled my conclusion here, in my mind the most powerful tool that we need to develop against cancer is early detection through screening, through screening that can be applied to everybody many times during their lifetimes. The good news, which is, of course, also a very painful news, is that for a cancer to develop for a normal cell to develop into a cancer cell, it may take 10, 15 years, in multiple different mutations, so that makes us feel very bad that we are not able to catch it and people die because of it, but at the same time, it should make us feel very good, that if we play it right and we develop the tools, perhaps it will be possible to intervene early on in the trajectory, identify where the tumor — the nascent tumor or pre-tumor lesion is developing and intervene with it, with a knife or some equivalent to the knife. We don't need new magic drugs.

But how are you going to be doing this risk assessment or this mass screening? Well, imaging, you know, x-rays, MRIs, C scan, this sort of stuff, that's great technology, very useful indispensable actually when you come to doing a diagnostic work-up but there are technical hurdles, if you will, that keep me in my mind from thinking of imaging as a way to do screening for everybody all the time in the future. What are those hurdles? It's expensive. The logistics are a problem. There is a burden of radiation that you need to take and there is a burden of — there is a limit in the imaging contrast that you can get, can you pick up a single cell? How are you going to identify a cluster of cells, so maybe 100 cells, how are you going to identify the molecular markers? For — as you know, every cancer is different, so identifying the molecular makeup is a fundamental necessity. Different cancers respond differently and only by understanding the molecular makeup [can] we can select the right drug, which now is called "personalized medicine" and if you want, we can talk about that, too.

So to me the way to address mass screening is through — you cannot think of doing biopsies on everybody, cutting people open all the time. That doesn't work either. So to me, the notion is can we take advantage of biological fluids, sputum, saliva, blood, the air we exhale, urine, any number of biological fluids and look into the molecular contents inside of these fluids and look for signatures. Now, let me tell you the bad news. Number one, there used to be a time when people thought that there were magic markers that you could use to say, "This person's got cancer". We don't believe that any more. There is no single molecule.

You can get a bit more, get a bit less, but the typical is not cancer-specific to the extent that we want. We need to look at combinations for different molecules, perhaps, 10, perhaps 100, some of which over-express, some of which under-express and they form a partner that is really indicative. That is, I think, the direction that we need to go at.

Now, what does this have to do with nanotechnology? Well, nanotech, how many proteins do we have in the bloodstream, how many different proteins do we have in the bloodstream? You know, one would think 30,000 genes, so maybe 30,000 proteins. How about a million proteins, maybe a million and a half, nobody knows for sure and let's include in that number also the proteolytic fragment that comes from the degradation of the proteins that tell us about the disease process. So a huge number of different proteins, we need to monitor. We have to have many channels that address each of those quantitatively in real time, cheap so we need to have sensors that will be able to talk with these molecules one at a time.

It stands to reason that they should be molecular size, that is nanotechnological by definition. In addition, I'll make it even worse, some of these proteins are so concentrated that they are 100 billion times more concentrated than some of the signatures we are looking for. So it's an unbelievable problem of unbelievable complexity. I think the only way to address that, you have to have tools the data sizes that are comparable to the molecules that they are looking at, many, many of them with very controlled properties. That's an operational definition of nanotechnology. This is nanotech. This is what I think nanotech is going to do to change the world. And this does not go in the body. It's a tool that you use in the laboratory.

So with that, risk assessment, mass screening, early detection, personalized diagnostics, so that we can then develop treatment that are personalized or modifications for the individual or for the disease or the stage, wherever it is when we are treating it and these treatments can be non-nanotechnological even though nanotech can help convey the drugs and the agents locally, and I will talk a little bit about that in a moment, reduction — these are the side effects, reduction in cost of medical care.

This is the statement to the potential. This is the "I Wish" list. Now, of course, if doing the most good is something we are interested in, we should try to knock down the barriers to doing the most good. Let me just mention a few of those and I promise I will pick up the pace a little bit. Of course, the root cause of all problems sometimes is that the science is not sufficiently developed for this particular question of the protein based or the proteomic screening and any number of other screening, the fundamental science, is really lagging behind but is making good progress.

Multi-disciplinary, to solve these problems we need to find ways to get together and break down disciplinary barriers, very difficult to do that in academia, unless we are actively working on that, this type of teamwork approaches will never succeed. Delay in developing a regulatory framework, and again, and I'm not saying this because Dr. Sanhei is here, but actually the FDA, I think, is doing a magnificent job in picking up the new issues that come with nanotechnology.

Delay engagement of private sectors, as far as I know all the new approaches always come to the clinic through some sort of a product. So whether we like it or not, that's what we got, so we need to find a way to engage the private sector to have transition optimally these things into the clinic. Educational practitioner base, development or reimbursement protocols, these are all barriers. To me the biggest barrier of them all is insufficient or delayed engagement of the stakeholders, that is the general population, which is why I applaud so much your interest in discussing nanotechnology. I spend a lot of time in Europe. The Europeans are very active in looking at the bioethical issues that surround nanotech, sometimes even keeping their clothes on, and they have all sorts of different ways. It's very interesting.

But I really think that is the key, so a strategy that we start to develop in the National Cancer Institute and then now I apply in my life in Texas, is that of engaging the advocacy groups, the National Breast Cancer Coalition or the Prostate Cancer Coalitions, the people that see in themselves or in their close ones, the ravaging effects of disease and can argue on the benefits versus risk from a personal involvement perspective. I think that is very helpful, keep things honest and balanced.

Okay, let's go the" first do no harm." How do we do harm? Well, of course, there's an opportunity cost. Again, this echos what Dr. Maynard said earlier on, there's an opportunity cost is the argument. Look at the disastrous situation that we are in, in particular with cancer. In 50 years, from 1950 to 2002, the demographics in just the mortality rate for heart disease got cut in half. Cerebral problem, strokes, hemorrhagic stroke for instance, vascular diseases got cut by one-third. Infectious diseases got cut in half. Cancer remained the same. So we have an issue. We have an issue. It's a very hard disease to fight. And great progress in some subsets, but overall the great killers remain great killers. 

So the opportunity cost, we have a responsibility, if we can do something about that, my personal take, just myself speaking, is that we have a responsibility to make things happen. Of course, as is true for every other field of medicine, we have to make sure that the treatment, the benefits outweighs the suffering and the risk, there's nothing new to that, of course, in any of these. It is all stuff that we apply to all of course, considerations of medicine. There is always the risk of device and system malfunctions and there is always the concern about causing health problems in the health care provider or in the non-patient populations such as the people — the family, for instance, or the visitors or whatever, of somebody that could be treated with nano. So we need to focus very carefully on all four of these and probably more.

Let me just make a quick comment on the environmental impact of medical nanotechnologies. Dr. Maynard is the world's expert and has given a tremendous presentation on his perspective in general, environmental impact. When it comes to medical nanotechnologies, of course, remember we had talked about a laboratory nanotechnologies, the things that we keep on the desk. I frankly have a difficult time seeing much if it as tremendous environmental risk from devices such as these and when it comes to nanoparticles for directed therapy, we recognize that these are nanomedicine type of formulations. They are prepared in regulated fashions, administered, disposed in controlled environment. They are presented in very low volumes.

Sometimes people ask me, "How scary is your nanoparticles you guys are making to deliver drugs such as methotrexate or doxorubicin or sisplatinum (phonetic)", and my answer is, look if I spend the rest of my life trying to make my particle as toxic as methotrexate, I don't think that I could. You know, the levels of toxicity of the drugs that we are using, we use them because they are so toxic, so there is an argument here of a comparison and of course, these are subject to regulatory scrutiny by safety by the FDA. So in a sense, I personally am less concerned about — we always need to be very vigilant always, we're advocating for very strict vigilance on environmental impacts but frankly, where I get terrified at night is not so much for — I'll tell you something else in a moment, but not so much about the medical nanotechnologies and their environmental impact, industrial, yes, I'm worried about that. I am personally worried about that, low volumes, no regulations, we don't know what the heck is going on, and so I'm concerned about that and I'm delighted that people are working on this and the more they work in on it, the better it is. 

Now, the question was asked, biowarfare applications was asked of Dr. Maynard. He fielded it very well. Let me give you one example that comes from the other thing that I wake up at night, that I woke up at night at times in cold sweat and this helps address — now, let's look at what nanotechnologies can do for delivery of drugs in a localized fashion. I want to make sure that my drug goes to the tumor, not everywhere else. Right now, by contrast, even with the best medicines that we have the molecular targeted medicines, I have to inject 10 to 100,000 molecules to get one in the tumor and the rest goes in other places where it does different degrees of damage.

The problem with that is not only biological recognition, everybody talks about that, there has been biological guidance to get your particle to the right place. That is a consideration but it is not the dominant consideration. In my mind, my dominant consideration is the biological barrier that the body puts up. A reference was made earlier to one, the blood/brain barrier. So we are chocked full of all of these booby traps and the barbed wires and things that the body has and that has developed and of course refined over 4 billion years or plus or minus a few, and that's the stuff very difficult to penetrate. It's there for a reason. And the drugs that we inject or the foreign substance that we inject, nanoparticles as well as anything else, had to negotiate those barriers. They're there for protective reasons. So we need to be able to deal with them in a way that is very selective. That story, like a hammer, like the wrench, it can be used for good, it can be used for bad. 

How can it be used for bad? For instance, this is something that actually comes over the research program that we work on but not as intensely as we used to. These are particles that contain agents, biological agents. These represent the inside of the intestine. This is the wall of the intestine and this is the vasculature that supports all of this. As you see, the wall of the intestine comprises this basement — this mucosal layer. We have an epithelial layer, epithelial cells, which are connected by this gate type of things, they're represented here as gates. So to get my drugs, think of insulin, why can't we take insulin by mouth? From here to here, there's all these barriers, very difficult to negotiate. So wouldn't it be great if somebody can come up with a way to make a pill that inside of this micropills is got not only the drug but doses of some agents that open up the gates so the stuff can come through and then they close up again, shortly after that. Insulin by mouth, great. You don't have to inject your kid eight times a day any more. Fantastic. 

Right, then the next guy over picks them up and uses then to turn otherwise very difficult pathogens of biological origin, and turns them into something that are no longer blood borne but they can be sprinkled on a salad or distributed in the water or made for people to inhale, how scary is that? Terrifying and the bad folks that may want to do that, have one great advantage over the medicals. They don't need FDA approval. 

(Laughter)

So one night literally I woke up and I said, "Holy cow," or something like that. What do we do now? And then I started having all these group meetings with all of our friends and advisers and whatever else and these are some of the options they came up and again, I'm just telling you our personal experience, but this carries through, I think, for essentially every piece of research that I can think about to different degrees. 

Well, we can stop everything, that's the Prince Charles approach. Prince Charles, as you may know, has advocated for a stop on nanomedical research until we figure something out. Well, that's an approach, and you know, the Europeans tend to have this notion, this concept of a "precautionary principle." I personally don't find that to be a principle but you know, this is a shorthand that is used to think that perhaps you shouldn't do anything until we know everything about that approach. And he's got good reasons, but to me, if you look at the four foundations of ethics, if you are the four pillars of the simple edifice that I was referring to, that has got all normal efficients without consideration for the other three. So I have a difficult time a little bit to accept that perspective, or we can continue research and just pretend we never thought about it. Or maybe we can tell everybody that there is a problem or that there is a risk or perhaps you don't tell everybody, just tell some people, the good guys.

And who? Or perhaps we say, okay, fine, but you know, in the back of the garage I'm also going to develop counter-tools if anybody comes up with bad ways to use this stuff. That is tricky, tricky. We have, of course, the U.S., who is signature to a treaty that says we don't do biowarfare research and to think of defensive measures, you have to think of offensive measures. And so we're in a bad position in certain circles, not far from this hotel. I was told very sternly, "I don't think that's a good idea." And that was a few years back. Maybe things have changed. But, you know, that's a real issue. And then let's have, okay, the other one that you're probably thinking about a little bit non-maleficence spelled yet a different way, unintended consequences. You may remember, some of you have seen this great development of a good friend of mine, Professor Carlos Montemagno. Now he is the Dean of the College of Engineering, University of Cincinnati. He's a great scientist. He took this piece of this biological enzyme, it's called FY NTPA, a fundamental enzyme for energy processing. It's got this rotatory motion in this piece of the molecule and he picked a piece of silicon made like you make out of — you know, when you make computer chips, I do a lot of those, I work in silicon myself. And so he was able to chop off this piece of the molecule, chop off — pick up a piece of silicon, put it in there and all of a sudden you have a nanopropeller, part biological, is an engine. They can use it to propel a submarine other than the physics doesn't support that. But this thing really spins and you can see it spinning water. It's exciting. Tremendous piece of science. So essentially here on a piece of silicon, manmade, computer type technology, you have been able to bring in biological capability. What is the bio-property? In this particular case the rotatory motion comes from a piece of biological molecules, great idea.

Can we extrapolate that to scary thoughts? Well, we can always do that. We can always think scary thoughts. I don't know if you read the book, the book "Prey." It's Michael Crightons' book that's got this self-assembling, autonomous, replicating nanoswarms and that attack people and end up eating people up and they have developed antangents (phonetic) of their own. So that's the doomsday scenario of nanotechnology.

Well, I don't think there's a chance that that will happen. We always need to be on guard. I don't think there is a chance that that will happen. So probably that's bad sci-fi, bad enough, it didn't even make it to Hollywood. And let me tell you I know about that a little bit. They were thinking about turning that into a Hollywood movie, but no, Hollywood movies like big scary monsters where you can have a lot of action. Nanoparticles, how are you going to visualize them? So where is the drama, where is the image of the nanoparticles are talking. The best that you can have is the guy, "Oh, I'm choking, I'm choking", which of course, we can do without the need for nanotechnology. Yet one more example of the fact that nano doesn't really bring anything new. It just brings some more heightened, if you will, degree of concern for things that you already had.

Respect, okay, to me respect has got a bunch of different components and again, excuse the power to my analysis. Informed consent is a fundamental component of respect, but you've got to know what you're talking about. So I mean, informed consent, how much harder is it to get the full informed consent with the respect for full knowledge of what is required for making decisions in nano. Perhaps there would be new angles that need to be looked into. Then the issue of performance enhancement was brought up already and I think some of the questions have already been mentioned. 

Okay, performance enhancement, I think we all agree what we should try to cure the sick but enhancing the normal, now what is normal? What is a tolerable risk? Can we decide, does the person decide, who decides what is acceptable? Having x-ray vision, is that acceptable? It's a trans-species type of thing that we should not accept. Who pays, who benefits? How is that nano different from coffee? You know, I take coffee all the time for enhancement of properties, and you know, steroids. I will not even mention the next one, plastic surgery, plastic surgery for cosmetic reasons. 

You know, the fact that you can get benefits from these is good and we are like that, but, of course, concerns come up. Let's talk about autonomy real quick, I'll come back to respect in a moment.

Right to make own decisions, now, let me tell you I've already given you a little bit

— a few items that come from the nano-world, that are already in clinical practice. Let me give you another one that is pervasive in every self-respecting biological laboratory around the country and probably the world. The microarray the DNA chip type of things for gene sequencing, that comes out. It is a straight up, brilliant application to biochemistry of a technology that has been used for making computer chips for about 50 years. That technology is called photolithography. 

So photolithography gives rise to the electronic chip which then gives rise somewhat in parallel to the micro-electro-mechanical systems which you may not know that you have but you have them in your car, for instance. These are the things that deploy the air bags if you hit something. There's many all over the place, sensors of that type which — and then the other generation is the microarray or the DNA which is called micro, you'll notice, it's not called nano. So why is it called micro? Because at the time these things were developed, about 15 years ago, close to 20 in the San Francisco Bay area, by a company called AFFYMETRIX together with Stanford, and I know because I was there, this little — this is a gene chip, one of the first ones that they put out. This little domains that you can use for sequencing the smallest you could make them was about 100 microns.

Now, with the technology evolution, it's kind of like the Morse law, the shrinking of all electronic components, the improvements in photolithography, the smallest you can make these domains is perhaps, 10 nano. Now, multiply out 100 micron, 10 nano, to get the image of surface area so what you're getting here is an enhancement of 100 million-fold worth of improvement and information density with respect to 15 years ago. That's a lot of million-fold. So now all of a sudden, the easy problem of genomics can be put in the context, different context, and we can start tackling the really hard problems of proteomics or all of the other omics that come on board and that is what people have been working on. 

So the notion is, nano is already pervasive in everything we do even in its early embodiment they were called micro because we weren't smart enough, it takes some time to develop these things, but the direction is that of mapping molecular signatures and... they can be gene products or they can be anything else but it's the same idea, to be able to pick up signatures that not only can tell us health and disease but it can also tell who we are, where we've been, who was sitting on this chair 10 minutes ago.  They are of course, I'm projecting now in terms of future developments, potentially. I'm looking at potential risks, or they can tell us what is the risk that I have of developing this disease, that disease, the other disease, which, of course, are issues that you have taken up already. But you know, these are a very fundamental enabling set of technologies. So who gets that information, a question of privacy? Who gets to make the decisions of what is the treatment that follows up in accordance with a certain risk profile?

What is the role of government in all of the above? Who is supposed to know these things? Who is supposed to know these profiles, the prognostics, the relevance of behavioral and environmental risk factors? Is it the person, is it the potential employer? Is it the insurance company? How do we treat? Again, I'm telling you things that you already discussed with great eloquence but allow me, just because they allow me to close the circle. 

Once we know the risk profiles, do we follow optimal care algorithms or do we have room for decision? What does this do with respect to autonomy of decision? Reimbursement, access to health care, employment discrimination, you may remember that there was a time to get married you needed to get a good health certificate including that you didn't have syphilis. I don't know if they did it in the country. They certainly did in Italy. 

Social interaction, are we going to have — do you see a society where I want your genome sequence before I marry you and I want to know the history of your entire [health] so that I can project what type of things you're going to get? Is that going to raise the spectrum of societal layering, those that have better chances and those that don't, and didn't mix. And perhaps those that have the better chance are also those that have the better resources to address whether problems may happen. Are we looking at societal layering? Now, I'm going out in the doomsday scenario myself. 

But I think I really resonate what Dr. Maynard was saying earlier, we kind of need to think these things out ahead of time a little bit and perhaps this is being very stupid. I'd be very happy if you do.

Justice, fair access to all. Will nanotech become yet another medical advance that will be of use only to the haves and inaccessible to have nots in the US and in the world? Now, that was the theme that I was given when I went to the Kyoto meeting on Science and Society in 2005. The other gentleman that was there to discuss these issues for the delegates there, it was a tremendous meeting, was Peter Singer, which I had never met before and I will confess I was a little bit tense about meeting. It turned out that it was an interesting set of discussions that we had.

So and the question that I was asked in the context of the society meeting was, "Tell us about the risk that nanotech will essentially contribute to the layering of the have and have nots by providing better healthcare only for the rich." And I said, "Well, of course, that's always a concern," but can't we for once rather than being defensive, think about — turn the argument around a little bit? Wouldn't it be part of our societal responsibility to turn the document around and rather than being defensive, focus on developing nanotech to specifically address healthcare injustices, healthcare disparities. There's a great opportunity for doing that. Single dose vaccines, you know, there are a large part of the population worldwide, if they see the doctor once, they are very happy. They may not have a chance to see a doctor again to get a booster shot for things that — for diseases that have all but disappeared from the developed world. 

Lower cost medication, I'll come back to that in a moment. Screening diagnostics, perhaps the biggest success that we have had in the fight against cancer is cervical cancer. Even before we get to the vaccines that are coming in now, because of what, because of the Pap smear. The Pap smear is a fantastic idea. It has reduced the incidence of the mortality of cancer in the developed world by orders of magnitude. Not so in under-developed countries. Why? You need to have a pathology lab to do a Pap smear. It doesn't do me any good if I don't have a team or trained technicians or trained doctors, the reagents that they need. It doesn't help me any. So for instance, I see points of light coming out this way and I'm very heartened by that. 

Some colleagues of mine at Rice University, Dr. Rebecca Richards-Kortum, is developing a colopscope (phonetic) that anybody can use, that lights up when you see something bad. You don't even have to know what it is, but it lights up and you can intervene directly. Portable system, but the ethical responsibility that we have is that we need to support these types of things. We can really change — nanotech can provide us with a set of tools that we can effectively use to address healthcare disparities but we have to get our act together and focus and really make it happen because this is, like all research, is expensive research, it's difficult research. It requires the environment, the organization, the skill, the priority, so I think that is an ethical consideration. 

Let me come back to this question of lower cost medication. As much as I'm trying to make a case for the positive things that nanotech can do, let me be honest with you, the one great example, the new nano drug that is coming to the market which I will not mention, but we talked about it earlier, it was the taxol, nanoparticle formulation, is so expensive, it's unbelievable how expensive it is. And frankly, that's yet another case of a drug that can really make a difference nano or no nano, which is priced with complete disregard, in my mind, for the cost of production. 

It's not how much it costs. I get asked all the time, "How much will your nanodrugs cost?" Well, if you look at the numbers, you know, the cost of the particle with respect to the drug, if you buy it on the open market, is minimal. It's small, it's pennies on the dollar, but that's not the point. That's not the price of drugs. These arguments that you hear, at least the way I read the arguments that I hear about how the prices of drugs is set and how much they have to do with the cost of production, the cost of exception, whatever else, are pretty thin arguments in my mind, than what I feel determines the cost of drugs and who gets and who doesn't is straight up market dynamics and I have a lot of respect for market dynamics, but perhaps, it is an ethical responsibility for us to find a way to balance the great strength of open market dynamics with ethical considerations and our societal responsibility, perhaps an in between type of an approach which of course, I'm not prepared to discuss. I wish I could but I think these are issues that perhaps this has to do also with the way we do research in universities, the way we do research in the pharmaceutical world.

We are getting products that cause this layering of haves and have nots because that's what we shoot for. Whether we do that consciously to subconsciously, I don't know but we are getting what we are getting up to do from the day one, perhaps developing different ways of setting priorities and directing research infrastructure can be — can address some of this. 

Well, you will be happy to hear that I've come to the end of my presentation. So let me give you a few summary points, at least the ones that I was not too afraid to put out in front of you and leave them there while we discussed some of the other ones that I mentioned, I left, of course, in the previous pages. So I think there are great opportunities for medical advances. I think that will happen. That's just my opinion but again, the best that I can do is speak my conscience to you. 

I think the environmental risks for medical nanotechnology are modest to very modest. However, for industrial nanotechnologies, I think that they need to be looked at with much greater enthusiasm than has been done so far. Military terror and risks in my mind are speculative and don't have any evidence that anybody is doing that of course, but that is something I do worry about and one reason for that is something Dr. Maynard said, that some of these things can be done in the back of the garage. It is not like putting together a nuclear power plant. The personalized medicine vision that we are all familiar with is really very much nanotech enabled both from the personalized diagnostics and the personalized delivery perspective so this then strengthens, should strengthen our concerns about the ethical questions of autonomy and privacy. I think there is a risk that nanotech will be available only to privileged societies, at least initially and there is one example that I mentioned I think should tell us a lot about that, that if we get our act together and act as a team should, I think we can direct nanotech specifically to address the questions of injustice and the question of underprivileged populations receiving a disproportionate low amount of healthcare. My personal take, and again, you ask, you know, somebody that's got a hammer, everything looks like a nail. I've been practicing nanotechnology, as I told you and there is a reason why I do that. So my last bullet point, perhaps, will not surprise you. I do think that the greatest risk in the nano medicine may be that of not taking advantage of risk for potential. And with that, I thank you very much for your very kind attention.

(Applause)

CHAIRMAN PELLEGRINO:  Thank you, Professor Ferrari for bringing some of the difficulties and complexities of nanotechnology down to the technical bioethical issues that we are concerned with. I'm sure that there are members of the Council who wish to comment and ask you questions. Do I see a hand? 

DR. FOSTER: Let me just make one comment. I, unfortunately, have got to go catch a plane. I'm actually going to get back to Dallas, but I want to say two things. One, I've been trying to understand what's happened to the climate in Dallas is this low pressure thing just sits there for 15 days with 8, 13 inches a day and I now think it's because this storm arrived in Houston and it's disturbed the whole atmosphere from Dr. Ferrari. 

Ben Carson and I were talking last night about the fact that there's an old biblical statement that without vision the people perish but the vision that you've brought is very interesting and touching and I just — particularly in medicine, I just — there's so many potentials for using this. How is a person like yourself as a leader in this, going to prioritize what one does first? And I'll let you answer that for the group, because I have to run. But I think almost everything that you brought up was both interesting, potentially exciting and then we also have all the things. I thought that it was really an excellent presentation.

But in your own mind, what do you think we do next? Are the vectors the main thing that we're going to start with?

PROF. FERRARI: Well, Dr. Foster, first of all, thanks for keeping the bed wet in Dallas, because in Houston, we are very happy that you are volunteering to keep that there. 

Yes, again, my personal answer has to do with I wish I could ascribe it to philosophical considerations but probably it's more contingency. I really — I am very strongly dedicated to breast cancer research and it is one of the primary focuses in my groups. And that, I think, evolved over the years because of opportunities and personal interest and also personal experience, but also opportunities. And this is a very important point about the community leadership that I would like to make on this.

However, a brief comment is that in my group we have — half of my group works in early detection systems and the other half works in targeting therapeutics. So that, I've told you, the walk that we walk. That is what we believe in. That's why we spend all of our time and energy and resources doing exactly these two things. There are many other things that one can do but that happens to be our focus specifically for breast cancer even though the developments — of course, the beauty of technology is, once you develop it for one branch of medicine, then it becomes pretty easy to apply to other branches of medicine. 

Now, why is breast cancer a particularly attractive area to work in, in terms of the contingencies of like everyday life? Well, you may remember that there is a great community group, the National Breast Cancer Coalition, which in years past, was able to harness — I think 12 years ago was the first year and bring down from the Hill something on the order of $150 million to be dedicated to breast cancer research through a mechanism that will really be controlled by the community itself. There was a tremendous paradigm shift. Rather than the traditional NIH mode, which a lot of us subscribe to, which is governed by scientists, this notion here it's going to be co-governed by community leaders with input from scientists and of all people, it's going to be administered by the Department of Defense, through the Army which had to do a little bit with the origin of the funds. 

Now, that program that has given way to — given the rise to —the Congressionally mandated Breast Cancer Research Program, which has grown to, I think, in excess close to $500 million a year. I think it's the biggest program that we have in cancer research, perhaps, even bigger than the NCI's, has also now spawned a program embraced prostate cancer and a few other things. Now, those guys, or those ladies, I should say, most not all, I was on the board for a couple of years, have a patient focus that allows them to push for taking great risks with respect to what the NIH typically does, so I found that to be a very suitable environment to direct our own programs because what we are doing really swings for the fences more than looking for a base hit. So as a result of that, you know, it's — we need to have a funding environment that is more prone to accepting risks. 

So by and large, the reason why we are focused on the breast cancer program is because the community has spoken, these million women have come together initially with a million women march, as it was called. It's always a million this, a million that. I think in that case it probably was a million people, and actually have made it happen for themselves and for the community that they care for. Initially, I'll be honest with you, I was terrified going in as a scientist into this environment, being on their board, being other things because I couldn't believe — I couldn't see how a group of ladies, 99 percent ladies, most of which with no scientific background, could be of any help in leading the fight against cancer. Now I've been five years with them, I've learned so much from them it's unbelievable. They help us keep on this and remember that our job is not to write books, it's not to give grants, it's not to do work on our careers. Our job is to work on improving healthcare and the ultimate objective to everything we do, is with a lady that's got breast cancer or that could get breast cancer and shouldn't get it. That's the reason.

DR. FOSTER: Thank you very much. Very moving statement.

CHAIRMAN PELLEGRINO:  Dr. Gómez-Lobo?

DR. GÓMEZ-LOBO: Thank you. It's very encouraging to have two Italians presiding this meeting. I am glad that you brought up the topic of justice, distributive justice and on a global scale. In fact, in my mind this ties in with our discussions — with the discussions we had yesterday about minimal healthcare in universal insurance and how — to what an extent it is a violation of justice that there be so many people without that kind of protection in the US. But my more specific question to you is the following: I personally don't understand the complex interactions between science, public funding, private funding, et cetera, but is there something like a dynamism that could really lead research into lower cost medication research in this area? I think what you said towards the end was extremely interesting, that there are a number of things that could be done for say, third world countries' populations if certain things were done.

Now, is there any hope in the, again, the dynamics of research as you see it, that would lead us in that direction?

PROF. FERRARI: Well, yes, thanks so much for a wonderful question again. Again, bringing things back to our laboratory, what we have done in my lab, we have hired as Director of our Breast Cancer Laboratory, a lady who by her day job she's a Reverend. She's not a scientist, and so her job is to review all the papers that we write before we send them out to make sure we are honest to our mission, to review all of our media communications, to review all of our patent applications, and to help us participate in guidance. She mentors everyone who is involved in breast cancer research and our work. Of course, she's got technical support but, you know, so that is a paradigmatic shift, if you will, bringing the community truly in an executive position in a control seat as opposed to being a boundary condition.

Frankly, my perspective has always been that unfortunately even, not only community involvement but in general there's always been a boundary condition to things we do in the lab. I think it is high time that that becomes the driving force, not a boundary condition. So in keeping with that philosophy, you're asking is there any dynamic that allows you to do that? Frankly, I don't think so. I think as usual, as many times as happened in the history of this great country, it really comes down to citizens taking life in their own hands and for instance in the case of the National Breast Cancer Coalition, in doing that philanthropy has been fantastic and again great efforts towards underdeveloped countries is spearheaded by the Melinda and Bill Gates Foundation. There are a number of other foundations. Michael Milken is doing great work with prostate, looking at things, approaches that can help address healthcare crisis in this country and internationally.

Now, in terms of I think that those mechanisms need to be enhanced and formalized. I think there is a policymaking aspect to that. That I think we need to come together and make the argument for formalizing approaches that will allow research, that will allow medical development to be directed specifically to those considerations. And that at this moment we are working on a policy document with somebody that I trust many of you know, Goran Hermeren from the University of Lund in Sweden. Again, the Europeans have been very aggressively considering bioethical issues, essentially a statement of responsibilities that have to do with what we as a society can do to help make sure that we channel resources in a way that will address the disparities and the inequities. Now, this gets a bit technical and I promise I will stop here, but there are very clear technical aspects for how we do research in the academic setting and in the industrial setting and they are very similar and they're mutually reinforcing that at the end, will always give us something that perpetuates the system that we have. So my perspective is, perhaps we can think out of the box and say a few stupid things and perhaps, over time, we will develop a way to engender a way of doing research and product development that does not bring us to this almost unavoidable conclusion of healthcare disparities.

Now, the notion of universal healthcare if very appealing, having been raised in Italy, there was ways in which that does not work, too. So I don't know that the reimbursement by itself is a solution. The way we bring healthcare, the mechanism of providing healthcare, above and beyond — together with reimbursement strategies, are also phenomenally important. There are types of medical products that regardless of the credible reimbursement policies that we can put in place, will never be available. So we need to focus on putting out things that people can use. That is my perspective.

DR. GÓMEZ-LOBO: Thank you.

CHAIRMAN PELLEGRINO:  Rebecca?

PROF. DRESSER: A couple of points. One is priority setting which is not, certainly, pertinent only to nanotechnology but is a broad issue problem in science. I'm a big fan of ordinary people getting involved in that discussion but there are a lot of problems, for example the National Breast Cancer Coalition, I think they're an excellent group, I agree with you. But of course, they're advocating for investment in a certain area and most of the advocacy organizations have their stakeholders. So — and everybody has a good cause. So how do we, from a broader level, make choices?

The NIH has some priority setting criteria such as promise and number of people effected by disease, number of years of average life span lost and so forth. But we haven't done a very good job of doing that thoughtfully. And then it depends a lot on lobbying. And so many poor people don't have the wherewithal to have an advocacy group and certainly in other countries. So there's a lot of unfairness there. And there are a lot of difficult moral questions such as what do we in wealthy countries owe in terms of investing our resources into the health problems of poor countries? 

I don't think we've done a good job of examining our consciences about that. So I agree with you that we should be involved in this but it is very complicated and I hope it can be done in a more thoughtful way and with awareness of the ethical complexities.

PROF. FERRARI: Yes.

PROF. DRESSER: And the second point is, maybe I'm jaded but you know, whenever a new area of science comes up, there's what I think it's Renee Fox calls Ritualized Optimism. So you know, we've seen this in so many different areas, genetics and stem cells and artificial hearts and everything. So we see it here. I guess I would plead for truth-telling and honesty about the uncertainty, whether the benefits will be achieved and openness and honesty about the downsides, the risks. 

One of your issues was shall we keep it secret, the risks or shall we disclose only to certain people? I think that the public is owed honesty in terms of what we have possibly to gain, but also what we have possibly to lose. So I would hope that the field would adopt that as a guiding principle.

PROF. FERRARI: Absolutely. Thanks so much. This was of course very wise and very inspiring words. And now, going backwards in the order of the presentations, or the items that you made, I certainly, I advocate, I agree with you in full that we need to be very open and truth-telling is absolutely necessary. Actually, in my earlier version of the talk, there was a slide that said cause for actions and then I didn't think it was my role to put out cause for actions and so I took that out. 

I had, perhaps, the strongest term of them all that I used today was scientists obliged to educate. You know, and so we can't oblige anybody to do anything but, you know, that is kind of the philosophy. I completely agree with you. We need to have forums or fora, whatever the plural might be, where we actually tell, and we need to be held accountable for our statements, somehow. I don't know how. The reality is that the word mechanism, you know, the word mechanism works against us. Let's be honest about this.

The word "mechanism," such as in all sorts of walks of professional life, the media, whatever else, I think it is true and I think nanotech suffers from a little bit of a tendency to sensationalism. I will also speak in defense, if you will, of the field a little bit. There have been many times that I've spoken to the media and I've been speaking in the most conservative ways that I could. The ones that I took were the ones that got everybody. And then I get every week phone calls, e-mails, letters from people that are in desperate situations that say, "You said that in the newspaper. You got this for this person, for me, for my father, for my daughter, for my wife," and those are heartbreaking stories. And every time I go through all of them and I listen to all them personally because they're so difficult to hear, and that has really put a great damper on my enthusiasm for speaking in general, you know, because then, you know, I'm called to the task.

That's one form of accountability. It's very painful from accountability, but I agree with you, we need to be — let's say one more thing, you cannot be a scientist if you're not an optimist. That is something I learned from Rick Smalley. He said, "Hey, come on. You can't fault me for being an optimist because if I wasn't, I couldn't be doing experiments. You know, why would I do that? Am I crazy? I do something that isn't going to work."

You know, so society, I think that interface needs to be monitored a little bit keeping this in mind. In terms of all we need to do, what our responsibilities are with respect to the rest of the world, I tend to be — again, that's just my personal take. I am not, I don't like institutionalizing things too much. I kind of like the personal charity that we model. Everyone in accordance with their own conscience and things. Just my take.

However, we can put together, because we're doing all sorts of other works, of our policy making without infringing on the individual liberties, but we can put together institutional developments, what I'm looking for, that will allow for the right results to come out. So let me put it this way, rather than having our research establishment work in a certain way, we can have our research establishment work in a different way. That is not mandating charity. I don't like mandating charity. That's doing the right thing. That is we're living up to our responsibilities in a great country. That's a different story. And I think that is the ethical choices we would prefer. We revamp in a sense, the entire edifice of our research and development in the country which is the most powerful on earth, in a way that we take into proper account the balance of the community.

Working solo doesn't work in the long haul, so you can even make a utilitarian argument for the country itself.

CHAIRMAN PELLEGRINO:  Professor George.

PROF. GEORGE: Thank you, Doctor. I think Professor Dresser has raised such an important issue about truth telling and I think the issue is not so much about outright lying or misrepresenting to the public. It's spinning, exaggerating a little bit, hyping, encouraging, more than is justified and I wonder if there's a deep problem here, perhaps unavoidable. The temptation to engage in those sins against truth telling may be just built into the fact that there is inevitably competition for scarce resources in the sciences for funding. 

And to sell the funding sources on my line of research, my area, rather than the other guy's, the temptation to say, "Well, there's greater hope here, perhaps than is justified," is just there. Now, is this an area where anything can be done? Is this an area where science can police itself? Is this an area where it's dangerous for any external bodies or institutions to attempt to police science? Is there any way within the scientific world that people can be held accountable for the hyping and exaggeration that goes on? Do you have any thoughts about this? I think it's just profoundly important.

PROF. FERRARI: It is profoundly important, I agree with you. It's — and you're right, it has to do with Darwinian dyanmics. It's Darwinian revolutionary privilege and advantages the scientists pursue because the reality is the bigger your name, the easier it is to get your grants, to get your promotions, to get those things. So it is very hard, it is very hard and I certainly, I don't mean for the nano or for everybody now, as was mentioned. It is difficult to make — to negotiate and I never would want anybody to police themselves on anything including scientists on their own, media communication approaches which is why, you know, knowing that the spirit is strong and the flesh is weak, whatever the expression may be, which is why I brought in the Reverend to make sure that she interfaces with every media communication that we make. It's very difficult.

So I think to have some sort of an external sounding board or I don't know, I think that would be very important. I would not know how to set it up. You also reminded me of another point that the Professor made, this question of setting priority, how do we set priority and man, I don't have a clue. The system, I think, the method that the NIH has put in place, I think is very strong and is very defensible, it's objective. It is based on numbers that anybody can control, go verify and so I think it's got great merit. However, you know, I'd like to think that perhaps, a way to avoid the disease wars, as we call them, you know, the breast cancer against prostate cancer against heart disease, against diabetes, everybody's got a great cause. But the way to avoid the disease wars is again, to restructure the research establishment to look at the things in common not at the differences. If you look, the case of cancer is dramatic in this — if you look at the fundamental mechanisms of cancer, you know, we think we bin cancers into place of origin just because that's the way we started looking at cancer a long time ago and we didn't know enough, so we're talking about breast as opposed to prostate as opposed to pancreas, as opposed to lung, but if you look at the fundamental science mechanisms, they are very similar. 

So the question is, can we redo the binning, very difficult to redo the binning because we are all protective of our turfs. Any time you redraw district lines, you know what brings, not far from here. So it's the same, the same, scientific redistricting is also very difficult and it's a very contentious proposition but I think that's an example of the things that we, as a community can do, which do not have anything to do with mandating charity or mandating people's conscience. It's just a better way to be addressing channeling everybody's resources to solve everybody's problems.

CHAIRMAN PELLEGRINO:  Thank you. I have time for one more question and one more response. Thank you. Leon?

DR. KASS: Thank you very much and thank you for this presentation. This is perhaps, not a question that should be addressed to you but I'd make a comment, because I'm trying to sort out given the presentations we've had this morning, what nanotechnology is such that we should give it separate treatment. I mean, what makes this a topic of special interest, let's say to a bioethics Council? 

And let me preface by making, perhaps, two philosophicalistic — more conceptual comment about where you begin, move to a comment you make in the middle and then in a way invite you to address a question. When you offer a definition of nanotechnology, the definition is confined to the device. I mean, the three parts really deal with the device. But — and a hammer is a device and these microscopic, less than microscopic things can be — there can be devices at that scale and they're manmade, et cetera. But a device makes certain powers available and those powers, then have multiple uses. The internal combustion engine is a device. Automobility is the power, the ability of people to move themselves around and you could use it to transport goods, to take yourself on vacation and to drive explosives into somebody else's buildings.

But still thinking further about what is technological, there are also attitudes and dispositions about problem solving and these things find their way into the larger socioeconomic and cultural context and ultimately with political and other kinds of notions governing, so that it seems to me there is partly a question of whether we are rightly understanding what we're about here if we're simply thinking about the devices without sort of elaborating, the larger possible meanings of what it is to be technological in general and technological on a nanoscale. 

In the middle of your presentation and several times and I don't disagree with this at all, you say there's a hammer and there's a wrench and they, like nanodevices, have their better and worse uses, et cetera. On the other hand, from the earlier presentation and from the comments made before, the very molecular scale of this, at least invites some people to want to group nanotechnologies together as a special source of concern. I mean, somebody said in the discussion afterwards, there's something insidious about this because it's sort of beneath detection and it can be spread around without people knowing it. 

I don't mean in the medical context but I mean — and I guess what I — with this sort of long-winded preface, do you really think that apart from gathering certain kinds of headlines, news support, galvanizing, the collaboration of physicists, chemists, physicians, engineers and so on, that from the point of view of thinking about the social issues or the ethical issues, that there's something unique about nanotechnology or is this simply a new wrinkle of the sorts of things about equal access, about privacy and things of this sort? Is there something special here and if so, what is it?

PROF. FERRARI: Thank you, Dr. Kass. My answer is that I don't think there is anything special about nanotechnology in terms of creating new chapters our consideration from a bioethical perspective keeping in mind the limitations on the bioethical understanding, I don't see there is anything new. I see for instance stem cells, there are truly different biological perspectives that were never discussed before, even though they have reference, of course, to millennia questions. For nanotechnology, I don't think so.

I think that what nanotechnology does, is whatever that is, is — heightens some concerns in areas that have already pretty well been understood and researched and studied so, perhaps puts greater priority for additional discourse and engagement of the community in certain areas because, for instance, there's matters of privacy and the acquiring of other data. Now all of a sudden this is happening today. It's happening tomorrow. We thought it would happen 10 years from now. We have to get our acts together in terms of the right say HIPAA laws or whatever modifications there are. 

So there's some policy making consequences that come from the fact that certain targets, I wouldn't reach that we did not think would be within reach very soon. So I think that is all nanotechnology. That accelerates the concern, the rate at which the concern must be addressed and sometimes, perhaps, heightens and intensifies the concern but I don't see anything that is conceptually another chapter in the great book of bioethics.

Something else that I would like to comment and I don't like the word nanotechnology I said earlier, not only because it has its roots in science fiction but also because you may have heard the expression, the nano is really a Greek prefix that means apt to bring in dollars from Washington DC. 

(Laughter)

That's what nano really means. And so now essentially the vast majority of what people are calling now nanotechnology is that we are — there is a lot of recycling going on, let me put it that way, and all sorts of other domains of science. All of a sudden they become nano and nano has become this big tent. I like tents, I like a lot of people. I'm a community type of guy, but it really has become on one side somewhat deceptive and I don't say that in a negative fashion but of course, it creates confusion because everybody is nano and everybody is not when it comes to getting considerations that actually come with that. So I think there is a little bit of three cards going on.

DR. KASS: Mr. Chairman, first of all, thank you for that, but I wonder — the time is out so we can't really do this now, but I would be very interested, after having heard this — these two presentations this morning, if Council members might be invited to write to you to see what answers they might, in fact, give in response to this question because it seems to me it bears upon what's at stake for this Council if we were to go further in this area. Bill Hurlbut in the previous session, I thought, spoke rather eloquently about the kind of consideration that might be unique to this.

I'm not sure that everyone would agree but if you would encourage that, I think it would be helpful.

CHAIRMAN PELLEGRINO:  I think that would be a splendid suggestion. We'd much like to hear from that because I think we're into a new area and I think the breadth of it has been exhibited here and the kinds of questions that Bill raised and you've raised need to be looked at in light of the practical suggestions that were put here before us. So I would welcome it. I think it's an excellent presentation. And with that, I would like to thank Professor Ferrari for his presentation and now we move into another aspect, the last aspect of our meeting, which usually is a time allowed for public discussants who many wish to say a word or two. They are required to register beforehand and I have before me only one person who registered. If there are others, they might rise later. The time is limited to the presentation. 

SESSION 6: PUBLIC COMMENTS

MR. HANSON: Thank you. Is this on? Thank you very much. I work on human genetics and nanotechnology at the International Center for Technology Assessment. I want to commend the Council for its opening entry into the discussion of nanotechnology. I think the principles of bioethics would be well applied to nanotechnology. We are working with a group of about 30 other non-governmental organizations, trying to look at what kinds of questions need to be asked about nanotechnology. We think some of our concerns actually amplify the traditional applications of bioethics. 

We do think that there are at least eight things that need to be carefully looked at and one is that there needs to be a precautionary foundation. We don't see this as a no but we think the precautionary principle needs to be applied to nanotechnologies largely because the existing science so far suggests that the release of nanomaterials, nanodevices or products of nano biotechnology may result in serious harm to human health and the environment. 

We think the second principle ought to be mandatory nanoregulations. The current legislation doesn't provide adequate oversight. And we don't think voluntary initiatives have been shown to be a good way to control technologies. The third point is we think that health and safety of the public and workers needs to be a paramount concern and that we need adequate information on this. I would say I think what we're learning in the medical applications of nanotechnology can be readily applied to some of the environmental and other human health aspects and I hope there will be ways found to do that. 

A fourth principle we see is environmental sustainability. Even in the area of medical applications, things get into the environment rather quickly. We have Prozac in fish that we didn't think were going to go there. So we need to look at how we monitor environmental aspects. A fifth point is transparency. We think the public's right to know includes labeling of all uses of nanotechnology. 

Interesting side note, Consumer Reports did their first review of nanotechnology looking at some sunscreens and they found of the eight sunscreens they looked at, all eight had engineered nanoparticles in them. Only one labeled it as having that, so how would a person be able later on to follow up what caused what? Fifth, public participation, we'd underscore Dr. Ferrari's comments about public participation and how much that can add to it.

The seventh point, we do need to look at the broader impacts. I think the example of taxol, nanotaxol, is a wonderful example of how the broader impacts need to be looked at. This medication has, basically just gone — taxol has just gone generic. It costs about $150.00 a dose for the generic. The nano version which in my opinion basically allows the extension of a patent, the nano version goes for $4,000.00. And it's not just rich people that are paying for this. 

It's all of us in this society because it's Medicare approved. So we do need to look at the broader impacts of all of this. And an eighth point, we believe liability should follow all the way to the end of the product, all the way through the life cycle. The insurance industry has concerns about this and we do, too. I'll finish up by saying that as the Council looks at all of these issues, I know all of you pay attention to this in other fields, but continue to pay attention to rhetorical contradiction. You have an interesting situation in the field where very often the same people call this revolution technology in one context and then they turn around and say it's ordinary, it doesn't need to be regulated. 

So you go to the Patent Trade Office, and say, "This is so revolutionary I need to get a patent on it, because it's never been done before." Then you go to the FDA and say it's so ordinary since we already approved taxol, you don't need to look at the separate aspects of nanotaxol. You've had a day and a half this long. I have copies of a paper that's nine pages long that summarizes papers that are longer that I'll leave with the committee and thank you for your work.

CHAIRMAN PELLEGRINO:  Thank you very much. As we close, your usually silent chairman would simply indicate that the ethical examination of these issues will go beyond the four principled approach. That heretical statement to be made by someone from Georgetown and I hope I'll not be ex communicated before I get back from lunch. But thank you very much.

(Applause)

(Whereupon, at 11:56 a.m. the above-entitled matter concluded.)


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