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Friday, June 29, 2007

Session 4: Nanotechnology: Benefits and Risks

Andrew D. Maynard, Ph.D.
Chief Science Adviser, Project on Emerging Nanotechnologies, Woodrow Wilson International Center for Scholars

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.


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.


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.


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. 


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". 


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. 


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.)

  - The President's Council on Bioethics -  
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