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Friday, September 7, 2007

Session 6: Nanotechnologies: Science, Risk and Ethics

Richard Superfine, Ph.D.
The Bowman and Gordon Gray Professor
Department of Physics and Astronomy
University of North Carolina at Chapel Hill

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

That's just scattering. 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Now, these particles and the sophistication of the particles in assembling them is quite amazing.  Here are particle arrays.  So I'm not looking at atoms here; I'm looking at particles.  So this here is an array of particles - this comes from taking a substrate and dipping it into a solution which has lead selenide particles, which are these larger particles here, and smaller gold particles. 

But they're in a solution, and they start attaching to a substrate, and they form this order array to the interactions between the gold particles, the lead selenide particles, and the surface.  See, you can form - see this one kind right here.  Here if I make the iron oxide particles larger, I can actually get multiple of the gold particles inside there.  And if I take triangular particles, I can get them to form these beautiful arrays.  These pictures just make me laugh when I see them, so feel free to go ahead and laugh.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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

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

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

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

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

DR. SUPERFINE:  Well, yeah - 

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

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

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

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

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

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

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

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

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

DR. HURLBUT:  Just one follow-up.


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

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

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


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


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


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


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

DR. SUPERFINE:  Yes, I do.

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

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

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

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

CHAIRMAN PELLEGRINO:  Any other comments?  Janet?

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


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

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

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

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

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

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

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

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

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

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

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

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

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

DR. SUPERFINE:  Twelve-inch wafers.

DR. KASS:  Twelve-inch -

DR. SUPERFINE:  Twelve-inch wafers.

DR. KASS:  Fair enough. 

DR. KASS:  Three-inch?

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

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

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

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

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

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

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

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

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

The issues for that, besides have and have not and changing what it means to be human, is how do you control the information?  Is the insurance company going to be intercepting that, or is somebody - an employer going to be intercepting that information?  Again, I think that's an issue that we're dealing with right now and not understanding in many ways how to deal with it.                      

And so I don't mean to be saying that nanotechnology presents no new issues.  I think it presents very serious issues, but I think they are largely issues which are already in front of us that we're struggling to deal with, and we would do well to deal with them.

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

(Whereupon, at 12:06 p.m. the above-entitled  matter concluded.)

  - The President's Council on Bioethics -  
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