Scroll to the bottom to see a video on the future of nano-gold.
Steve Mirsky: Welcome to Scientific American's Science Talk, posted on October 15, 2014. I'm Steve Mirsky, and joining me from our Washington DC bureau is Scientific American's senior editor Josh Fischman. Hi Josh.
Josh Fischman: Hi Steve.
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Steve Mirsky: Josh, tell me what we are about to hear.
Josh Fischman: Well, Steve, on August 18th of this year, I was part of a panel at the University of California, San Diego, discussing the latest advances in nano science, and the panel brought together three eminent nanotechnologists to talk about their latest work and it was done under the auspices of the BBC World Service and their radio show, The Forum.
Steve Mirsky: And you're on the panel as obviously not a nanotechnologist, you're the science journalist there to try to help provide some perspective and background?
Josh Fischman: That's right, I'm there because I've been covering nano science for a number of years and I'm the one who can explain that when you say nano you mean a billionth of a meter.
Steve Mirsky: That's a very important point.
Josh Fischman: It is, because you're getting really, really small and the point of the panel was to talk about what you can do when you get that small. The panel included Shana Kelly, who is a biochemist at the University of Toronto who's been developing nano scale diagnostic chips that can detect pathogens in the blood. There was also Yamuna Krishnan from the University of Chicago who makes experimental machines out of filaments of DNA and gets them to sail into the little crannies of living cells.
And we had Benjamin Bratton, who is a theorist at the University of California, San Diego, and he's been working on the concept of nano skin, which ranges from tattoos to paint on a wall embedded with sensors that can detect environmental changes like say smoke or a chemical attack.
The panel was moderated by the BBC journalist Bridget Kendall.
Steve Mirsky: Excellent, so without any further ado, Josh as I think it was Steve Martin who said let's get small.
Bridget Kendall: What's the smallest thing you can think of? Smaller than anything you can see with a naked eye? Take a strand of human hair, for example, and imagine splitting it crossways 100,000 times. You can't see it or even visualize it with the mind's eye, but you've entered the realm of the nano scale, where one nanometer is one billionth of one meter, and this it the world that we want to explore on the forum today.
We've come to San Diego in southern California and in front of me is an audience including many scientists who work in this area, the increasingly important field of nanotechnology. They’ve come from all over the world to join the Royal Society of Chemistry Meeting Challenges in Nanoscience to pool expertise on the latest research, and I'll be asking for their thoughts a little later.
But first, I'm pleased to welcome to the stage here in the ballroom at the University of California, San Diego, professor of biochemistry at the University of Toronto in Canada, Shana Kelly. Associate professor at the National Center for Biological Sciences in Bangalore, India, Yamuna Krishnan. The director of the Center for Design and Geopolitics here at the University of California, San Diego, Benjamin Bratton. And senior editor at the Scientific American magazine, Josh Fischman.
Now, the words nanotechnology, nano science, nano scale have become part of everyday speech, but the question is what does nano really mean? And let's focus on scale to start with. Can each of you here on the panel, from your perspective, tell me is there a point beyond the things that you deal with, think about, work with, just become too tiny to be able to deal with them?
Yamuna, you make tiny nano machines out of synthetic DNA to insert into living cells. What do you think?
Yamuna Krishnan: So I think I'm working at the limit of nanotechnology, because a filament of DNA is actually two nanometers thick. Any less and you would start getting into the angstrom scale and that would be out of the realm of nanotechnology.
Bridget Kendall: Angstrom scale? What does that mean?
Yamuna Krishnan: That's a tenth smaller, the level of atoms, than the nano scale, which is one nanometer to roughly 500 nanometers.
Bridget Kendall: Okay, Shana, what about you? Your nano enhanced electronic chips can test for harmful pathogens with unprecedented speed. What do you think anything this question of scale ?
Shana Kelly: Well, I think it's true that there will be a scale that's too small for a nano technologist to work with. We only have so many tools that allow us to visualize what we're working with, and if they can't resolve the structures that we're looking at, then there's nothing to see.
Bridget Kendall: So that means it's limited by the tools that you have to look at them.
Shana Kelly: In part, yeah.
Bridget Kendall: So it could change.
Shana Kelly: It could change, absolutely.
Bridget Kendall: Josh, what do you think? You're a science journalist who's been following this field for many years. Do you think this is a moving scale, the nano scale?
Josh Fischman: I think it is a moving scale. I agree with Shana that it really depends on the tools that are available to look at what you want to move around on this very small scale. Richard Fineman, the Nobel prize winning physicist in 1959 kind of kicked off the idea of nanotechnology with his lecture saying there's plenty of room at the bottom, and that was 40 years, 35 years before anybody invented anything – any microscope that could move these atoms around. And so we're continually thinking very far ahead of the tools that we have available and the tools eventually catch up.
Bridget Kendall: Benjamin, you're in the business of thinking, you're a designer and a theorist, and you've worked in nanotechnology not as a scientists but more from the point of view of being a designer and an artist. What do you think about this?
Benjamin Bratton: Well, as a designer I work with the nano science and nano engineering that others have accomplished, usually working with solid science. And so the way I think about scale and work with it is less about what exactly is going on at the nano scale than how that might affect what's going on at much larger scales, the scale of the human body or urban scale of scale of ecology and how it is that we can think about the nano engineering at an infrastructural scale. So for me, it has more to do with how big it can go rather than how small it can go.
Bridget Kendall: So thinking that bridges the very, very small and sometimes the very, very big. We'll hear more about that in a minute, but let's bring in the audience here with us in San Diego. I wonder those of you who are here with us, how many of you work with nanotechnology or in nano science, let's have a show of hands. Who's in this field? Okay, a forest of hands has gone up. Not absolutely everybody, but a lot of people.
And we're interested to get your views on this question of scale, what do you think it is that sets the boundaries of the lower end of the nano scale where nano technology stops? Yes.
Nathan J_____:I'm Nathan J_____, I'm a professor here in chemistry and biochemistry at UC-San Diego. I think there are a lot of chemists here who would say that when you probe below a nanometer, you start actually doing chemistry. And so there are a lot of tools for probing those kinds of ______. In fact, to small molecule chemists, nano scale materials are huge, and intractable precisely because of that. So the biggest problems in characterization come at the long nanometer scales as you approach microns.
Bridget Kendall: Okay, another contribution from the floor, how does these thoughts relate to your research? Yes.
Craig Hawker:My name's Craig Hawker and I'm a professor of materials at University of California, Santa Barbara. I would like to remind everyone that nanotechnology has been around for a long time. Medieval artisans used nanotechnology for stained glass windows. They didn’t understand the atomic or the molecular rationale behind what they were doing. We now appreciate and understand cause and effect, but nanotechnology per se has been persistent for a long, long time.
Bridget Kendall: Thank you. That brings me on to something I wanted to ask you, Josh, which is it's very hard to imagine the nano level. It's easier to grasp the way that it affects our lives, but just for people who are just trying to imagine exactly what it is, nanotechnology, can you sketch out the range of tools and products that we are now beginning to understand and manipulate and benefit from?
Josh Fischman: Sure. Carbon nanotubes that make up racing bicycle frames, antifouling paint for buildings and for boats, golf balls that fly longer when you hit them, which I know is something the everybody is very happy about, tennis rackets made of carbon that hit a ball straighter. This all sounds like it's a bunch of leisure activities. Sunscreen, so I think that that's the consumer products realm.
And then what is probably more interesting, building diagnostic devices that are just a few nanometers big that can sense changes in molecules which can signify the difference between health and disease. Or that can form the paint on the walls that can detect a fire.
Bridget Kendall: Well, let's hear a bit more about that, and come to your research, Yamuna, because you work in the field of genetic biology and medicine. You work with nuclear bases, which are the building blocks of DNA, and in your lab in Bangalore in India, you knit them together.
Yamuna Krishnan: Yes.
Bridget Kendall: Into what amounts to a synthetic strand of DNA, I suppose, sort of tiny, biological nano machines which you then dispatch into the nooks and crannies of cells. Let's start with scale. A strand of DNA is how small?
Yamuna Krishnan: Is two nanometers thick.
Bridget Kendall: So how do you actually see and work with things at that level?
Yamuna Krishnan: So you use special microscopes, these are called atomic force microscopes, which detect the object sort of by feeling it rather than using the wavelength of light, because many of these objects are smaller than the wavelength of light, which means they cannot be seen. So they have to be visualized by somehow feeling them with these atomically thin or atomically thick needles. That's one way. The other way is to use methods of spectroscopy to sort of visualize their structure. But essentially what our lab does is to use DNA like wool and knit it into various shapes. Just the way that you can take a piece of wool and knit it into very, very different kinds of shapes like a sweater or a sock, using the same piece of wool what is the difference is where you make the connections. Which points are connected to each other, and in the same way, using DNA, you can change the connection points by joining together different domains, and you can define a domain by the sequence of nuclear bases that you have on this filament. And in this way, by adding different strands of DNA in the same – in a solution, I heat it and cool it in a specific way, you can get it to fold and knit itself into these very interesting shapes that form the body of a machine that we then get to sort of sail into a living cell, very specific environment, inside of a living organism and then report to us the concentration of some interesting chemical in that place to tell us a little bit about the health and disease state of that cell.
Bridget Kendall: So can you give an example, what might this little probe be telling us about this cell?
Yamuna Krishnan: So our very first attempt was to measure something very fundamental, the most fundamental form of chemistry you can think of is actually the acidity level of the environment. And so we've made a pH sensor, and this is a small DNA device that can go very specifically into a very defined micro environment of a living cell and report to us what the pH or the acidity level is in that environment.
So why would this be important, right? Because if you look at something like the lysosome, it's a certain little compartment inside of a cell, if the pH is not exactly the value that it's supposed to be, it results in several different disorders. And I think you have now about 50 different types of rare disorders that are called lysosomal storage disorders that are all related to altered pH in that environment. So now you have the basis to be able to pick up these diseases possibly earlier, rather than later.
Bridget Kendall: Benjamin, you were saying that you think about how the nano world can be related to the human world. Listening to Yamuna, what are your thoughts of the application for this sort of thing?
Benjamin Bratton: It's tremendous. We can talk about machines or devices or something that we make at the nano scale, but like any technology, it's always working in relationship to other technologies. One of my – the design interests that we have that we're working a lot is the relationship between nanotechnology and internet of things, and particularly the way in which nanotechnologies can function as sensors of events that are happening in the environment or perhaps on a body or in a body, and how that sensing becomes information, which can then be made part of a local or larger computing environment which would link nanotechnology to cloud computing in general.
And so on the one hand, we see a lot of interest in this around what's called quantified self, of how it is that you could measure say the athletic performance a – of one person. But this starts to get really interesting when it's not just one body or one person, but it's a whole population of people, the kind of data that can be generated, the kind of tools that we can imagine and that we can make that are sensing something happening from one body but then also affecting it back, as well.
Bridget Kendall: So Yamuna's talking about sensors at the DNA level, right? And you're talking about something else, because you have got involved in a particular project, haven't you, called nano skin, which is also about sensors.
Benjamin Bratton: It is, yeah. And this – all the nano science that this project was based in is all based on the work of Dr. Joseph Wang here at UCSD, as well. And it sort of starts with a – not really with a scientific question than more with a design or experiential question. And that is with cinema and photography, we figure out how to augment or transform the way in which we saw. With audio technologies we're able to transform the sensing of how we hear.
But our largest sensory organ is our skin, and the ways in which it might be possible to reimagine or redesign how it is that skin senses the world around it is sort of the larger area of investigation. And so Joseph's laboratory came up with these inks that were able to sense the particulate matter of chemicals that are commonly used in IEDs, explosive devices. And we began working with them and thinking about them, and they had done these really interesting temporary tattoos that would allow for this sorts of sensing at the level of the skin.
But we also came up to this idea that paint is just ink at a larger scale. And so if you use this as the skin of a building, the skin of an environment, then the environment itself can be a sensor. So it's the difference between sensing and sensation, perhaps, for people –
Bridget Kendall: You know, I find this really creepy, this idea [laughter] that whole buildings [Crosstalk] could be out there tattooed with sensors which could sense us as we go past, that's what you're talking about, right?
Benjamin Bratton: It is, yeah, and I think like any good design, if we're not quite sure of whether it's a good thing or a bad thing, we might be onto something interesting. So there absolutely are both positive and negative use cases to be derived from this for sure, but that's what makes it interesting as research.
Bridget Kendall: Well, that – I wanted to pick that up with you, Yamuna, because sensors you can see how these sorts of little knitted DNA could be useful in detecting disease or presumably for all sorts of things, like for example treatment for cancer, potentially. But what about the dangers? What about the potential health issues from these artificial DNA strands? Because they may be a means for gaining information, but what are they doing? For example, if you get to the point of synthetic DNA being inserted into the human body, how do you know what happens when it accumulates?
Yamuna Krishnan: So that's a very interesting question, and I just want to place that in perspective with any new chemical that comes out as a drug. It also has its own side effects. That doesn't mean it's bad. But I think it's very important to proceed with a tone of cautious optimism. It's very important to understand that when you're dealing with DNA, you are dealing with something that can evoke what's called an immune response, where you could have an allergic reaction, so to speak, from the body.
But then you also have these sort of side effects with other chemicals, as well. Now, the special thing about DNA, especially when you're sort of triggering something called the immune system, is that it's not a bad thing. If you can learn how to control that immune response, so you could use this for immunotherapy, for example, and that's what many Immunotherapeutics are doing. They are tuning the immune response of the body, where you can get cells to kill themselves in a programmed way.
So you might even be able to harness the immune system, at the same time deliver a drug. Now, I'm not saying that DNA is going to be the one answer to every single question, but I think it could be a very powerful answer to some things.
Bridget Kendall: The key word it seems to me there is harness, that you can still keep hold of the reins. Josh, what do you think?
Josh Fischman: The thing that's been picked up by the popular press and also by science fiction writers is the autonomous or semiautonomous nature of nanotechnological devices or treatments, that Bridget you said harness, that you can get hold of it and – but if they're autonomous –
Bridget Kendall: You just nudge them and they go their own way, and where do they go?
Josh Fischman: Maybe we can't get hold of it. On the macro scale, if my refrigerator starts misbehaving, I can throw it out. If there is a little sensor in my blood made of artificial DNA, what if it self assembles into something else?
Yamuna Krishnan: I think there's one thing that we should sort of understand which is that yesterday's science fiction is tomorrow's reality. And you're talking about ingesting particles that might possibly integrate with our systems and stuff like that, but I just want to say that you should also think of these kinds of technologies as when you go for magnetic resonance imaging, you are injected with a stain which then is leached out of the system. It's not something which sits in the body forever and ever. And I think that's a property of many biomolecules and biological technologies that are based on biological scaffolds, that they can be degraded by the system. If you stick in the right molecular programs for that degradation [Crosstalk].
Josh Fischman: So what you're saying is the body naturally likes to tear DNA apart and that's a natural sort of fail-safe mechanism.
Yamuna Krishnan: So the tearing apart of DNA can give rise to two things. It can either degrade it or it can give you an immune response, and if you can control both of them, then you have the basis of a very powerful way to interrogate living systems.
Bridget Kendall: Shana, you're a professor of biochemistry, can you put it into context for us?
Shana Kelly: You know, one thought that I had when we were talking about DNA self assembling in the body because you program DNA to do one thing, have it do something else is that we should recognize that many biological processes that are just in nature, it's exactly the same stuff. I mean, and even many medical problems. I mean, we have types of cardiovascular disease that result because you have plaques that self assemble. Neurodegenerative diseases because we have plaques that self assemble in the brain.
So a lot of the phenomena that we're talking about putting to work hopefully in good ways, those same phenomena are already present in nature.
Bridget Kendall: You're developing devices to make the diagnostic testing of a single drop of blood or urine much quicker without the need for complicated lab equipment. And at the heart of this are electronic chips with tiny amounts of gold and another metal, palladium. Can you tell us how this chip works?
Shana Kelly: Sure. So we take things like silicon chips, we functionalize them with nano materials and then we coat the nano materials with molecules that are able to specifically recognize other molecules in a sample. And so they're able to bring that molecule to the surface of a chip and then we use electrical signals to have the device tell the user that the molecule has been detected. And so this is – it's a matter of measuring very small electrical signals and turning that into information about what's present in a sample that's been taken from a patient.
Bridget Kendall: And why the nano particles of gold and palladium?
Shana Kelly: So the nano particles are there really as a material to support the recognition event, and the fact that they have very small dimensions helps them be much more effective in finding the molecules.
Bridget Kendall: And they're not just fast, they're also smart, aren't they, distinguishing different strains of bacteria, including the ones that are resistant to antibiotics.
Shana Kelly: That's right, and that's our using all the genetic information that's out there that people have collected that tells you whether the piece of DNA that you're detecting belongs to one type of bacterium or another or one that has antibiotic resistance. And so we're leveraging the biology that’s already out there .
Bridget Kendall: So it's quite a – this is quite a big practical difference, isn't it? If you're waiting for a blood test, you sure want to have it in minutes rather than a couple of days. It could be critical.
Shana Kelly: It could be absolutely critical.
Bridget Kendall: But the interesting thing is that people tend to think of nanotech as being very expensive to develop, but you – I think you've said that you're hoping that these devices, because they are so quick, that they could roll out and be used in developing countries.
Shana Kelly: Yeah, that's absolutely true. Nano materials don’t have to be expensive. I mean, that's one of the things about using nano particles of gold is that that's a very, very small amount of gold. And so using nano materials rather than bulk materials can be very cost effective.
Bridget Kendall: What do you think about that, Yamuna, especially coming from Bangalore in India?
Yamuna Krishnan: So I'm really happy we brought the developing world into this discussion. Most of the time, many people are actually illiterate, and so the challenge when they go to a doctor is to actually be able to deliver them a very fast diagnosis, because that guy is not going to come back again the next day for another round of what do I have. So you have a very small window of time to be able to figure out what this guy has and to be able to prescribe the right antibiotic.
And actually if you look at it, a lot of antibiotic resistance strains have actually emerged from the developing world, where people have not actually completed their courses or taken the wrong antibiotic, because the doctor has to usually prescribe on the basis of some heuristic information. And that's where I think this actually can have a huge impact, so I'm very excited about Shana's work.
Bridget Kendall: What do you think about this, Benjamin? Because I think that quite a lot of people are – have the feeling that the advances in biomedical science, we're probably going to make medical treatment more personalized, targeted to the genetic character of individuals, which will be a good thing, but probably it'll be only available for elites and people in rich countries, that it wouldn’t be able to roll out because it would be a bit exclusive. But actually what we're talking about here is the complete opposite.
Benjamin Bratton: Yes. It's complicated. We think about the Ebola case, you imagine how wonderful it would be to have some sort of mechanism at the airport, for example, to make sure very quickly before people get on planes whether or not something like this was spread, and this as well. And at the same time, part of the reason it spread is because there was such widespread distrust of the government and the medical community in Sierra Leone, east Sierra Leone in particular.
In other words, no single technology by itself works to solve any of these problems. The way in which it works, whether it's successful or not successful, whether it's a good thing or a bad thing, in many cases isn't determined by the technology itself. It's determined by the rest of the cultural, political, economic context in which that technology is used.
But to your point of the personalized medicine, it may actually be inverse, and this goes to the question I think you were raising before about this work and privacy. It may very well be that it's the relatively disadvantaged, those who are relatively unprivileged who don’t have or aren't able to pay for privacy are the ones whose genomes will be most monitored, most medicalized, most intervened upon, as opposed to the other way around.
Bridget Kendall: That's an interesting thought. Let's throw that to the audience, the future of medicine with the use of nanotechnology. What do you think about this? This gentleman in black.
Graham L_____:Graham L______, the University of Sheffield in England. I actually think that these technologies can benefit lots of people and not just the wealthy elite. There've been some really exciting developments recently in low cost, portable technologies for diagnosis of disease. And there are real, very exciting possibilities that these will benefit people in poor countries who don’t have access to the kind of health care that we have in the West. So I hope the benefits will be quite widespread.
Bridget Kendall: Other people, what are your views on this? Yes, there's a lady here in blue.
Catherine M_____:Catherine M_____, I'm a post-doctoral fellow at MIT. I think this is an amazing opportunity of the interface of information technology and nanotechnology. Just like we have now personalized computing, most people have a personal computer or a cell phone, and that interface or that cell phone or computer is your personal monitor or detector, and you have a nano scale device that interfaces with that technology. I think it's an amazing opportunity for bridging the two technologies.
Bridget Kendall: Let's just focus for a moment on something that we haven’t talked about quite so much, which is not just the size of the nano scale but also behavior. Because very small things don’t behave in the same way they do at a normal scale, do they? Josh, can you give us some examples?
Josh Fischman: Think of a marble. One that you can hold in your hand. And if you try and whack that marble with something very, very small, like an electron or a photon, probably nothing is going to happen, or at least nothing that you can detect. But if you carve that marble up into a billion pieces, you've created a much greater surface area from that marble and each of those billion pieces is now small enough to be effected either in terms of how it conducts heat or light or electricity when that electron or that photon whacks into it. And if those billion pieces are close enough to each other, there might be some sort of domino effect whereas piece one knocks into piece two, and you have kind of this chain reaction that ripples through the entire field of what used to be a marble.
Bridget Kendall: Shana.
Shana Kelly: Gold nano particles are not gold colored. So if you have enough gold nano particles to be able to see them with your eye, they're actually red. And that's a great example of something just because it's nano structured having a very different property that you can actually see and it has to do with the fact that gold nano particles, they're down – the dimensions are starting to be the dimensions of wavelengths of light. And so light interacts with nano materials very differently than it interacts with bulk materials.
Bridget Kendall: What about you, Yamuna?
Yamuna Krishnan: So my favorite example of this unusual surface area to volume ratio that you find in the nano scale is sort of if you take a polymer deposited nano composite, which is this marble let's say which has been made into small nano particles, and you take one – something which will fit a teaspoon full of that material, just a teaspoon full, and you calculate the surface area, it's the area of a football field.
So that's 700 meters squared, the area of a football field contained in the volume of a teaspoon.
Bridget Kendall: Shana I just wondered, how much is there we still need to learn about this at the nano scale, this different behavior?
Shana Kelly: Oh there's so much to learn. I mean, we're hearing about new discoveries every hour that we sit through the sessions at this conference, and it's – I don't think there's any limit to what we still have to learn.
Bridget Kendall: Thank you all very much, and thank you, too, to our audience here in San Diego. Shana Kelly, Yamuna Krishnan, Benjamin Bratton and Josh Fischman, and it's goodbye from me and from all of us here.
Steve Mirsky: That's it for this episode.
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