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Nanobots today
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  NATURE NANOTECHNOLOGY  | VOL 8 | JULY 2013 | www.nature.com/naturenanotechnology  475 thesis Nanobots today Nanobots have in the past been a fixture of science fiction writing and illustration, and such ideas are now also appearing in scientific research. But, as  Chris Toumey  explains, practical nanobots are different from their science fiction counterparts. Science fiction writers produced stories o miniaturized machines long beore the prefix ‘nano’ was crafed to mean a billionth o a metre (or a litre, or a gram, and so on) 1 . Te most amous o these machines was the Proteus , which appeared in the 1966 film Fantastic Voyage . In the film, a small submarine and its crew were temporarily miniaturized or the purpose o saving the lie o an important scientist by entering his blood stream and destroying a clot in his brain. Tis was good science fiction, especially the urgency or the crew to exit the patient’s body beore they returned to normal size.Some 20 years later, as nanotechnology came to the attention o a new generation o science fiction writers and antasy illustrators, the theme o ultra-miniaturized devices blossomed again. Tree kinds o nanobots (abbreviated rom ‘nano-robots’) populated latter-day science fiction illustration. Te first was a amily o machines with the abilities o mechanical diggers that would excavate plaque and other nasty substances on the inside suraces o our blood vessels. Te second was a group o submarine-like vessels that would locate viruses and other pathogens, and then destroy them with lethal rays. Te third was the nano-louse, which had mechanical claws to seize a red blood cell and insert a needle into it. Te pictures o nano-lice seemed especially vivid in conveying the idea that nanomedicine would soon have the ability to cure diseases by using a remarkably precise device.Brigitte Nerlich explains that illustrations o nanobots were intended to make nanoscale machines seem real, amiliar and beneficial 2 . Nanotechnology would be acceptable to non-scientists i they judged it in terms o these pictures.And yet there was a puzzle in the portraits o the nano-lice. What exactly were they doing? Once when I was leading a discussion o nanotechnology with a group o high-school students, we observed a picture o a nano-louse, and one o the students asked what operation it was perorming. Some students thought the needle was injecting a substance into the red blood cell; others said it was extracting something; a third group said it was doing neither, but merely grasping it firmly so it could move the cell rom one place to another. Te answer, I said, was that it was doing whatever the illustrator meant or it to do, even though we could not tell what the illustrator had in mind. Tis raises a good caution: it is not a good idea to create a picture o what nanomedicine can do i it leaves the viewer wondering what the device is doing, with three equally plausible answers.Another irony is that these supposed nanobots are not nanoscale. I they were real they would be measured in micrometres, not nanometres. Tey are approximately the size o one or two red blood cells, which are usually 5 to 10 μm in diameter. And although it is possible to make moving parts at the scale o micrometres, there is no control system — no on-board microcomputer — small enough to make each o them behave the way their illustrators suggest they would. And no such thing is on the horizon.With or without these caveats, nanobots were especially prevalent in a window o time rom about 1999 to 2001. Andreas Lösch explains that illustrations o nanobots in German media served as a device by which scientific, economic and mass media discourses could each project optimistic visions o the uture o nanomedicine. Scientists were srcinally comortable with these illustrations, says Lösch, but they later eared the nanobots had a “weak reerence to current developments in nanomedicine” 3 . Tis was a polite way to say that scientists did not want to be held accountable or A computer-generated illustration of a nano-louse attached to a red blood cell.     ©    C    O    N    E    Y    L    J    A    Y    /    G    E    T    T    Y    I    M    A    G    E    S © 2013 Macmillan Publishers Limited. All rights reserved  476 NATURE NANOTECHNOLOGY  | VOL 8 | JULY 2013 | www.nature.com/naturenanotechnology thesis the extravagant expectations o naïve non-scientists.In April 2010, Michael Cobb conducted survey-based research on public expectations or nanomedicine 4 . Interviewees read an optimistic article about nanomedicine; one group also saw a picture o a nano-louse, which illustrated the article, whereas the other group saw no illustration. In Cobb’s words: “Respondents were slightly less supportive o nano i they saw the image”; “Tey were also a little a little less likely to report that it would be beneficial”; and “Te image appears to increase uncertainty among the uninormed”.So much or the idea that nanomedicine automatically benefits rom pictures o nanobots.Even though that idea is problematic and even misguided, there are other devices at another scale, which are also called nanobots, and their grounding in reality is more credible than the nano-lice. Molecular-scale devices (measured in nanometres) are being built to target, penetrate and destroy cancer cells. One good example is rom Shawn Douglas and colleagues at the Wyss Institute at Harvard University who have built a molecular-scale device to attack cancer cells, and to leave normal cells alone 5 . Tis is, in their words, “an autonomous DNA robot capable o transporting molecular payloads to cells”. Te first step towards this device is an exercise in DNA srcami, which is to say that strands o DNA are linked to orm two-dimensional suraces, and those suraces can then be olded into three-dimensional shapes, including containers that open and close. Inside an srcami structure are placed two molecular payloads: a gold nanoshell o 5-nm diameter and a ragment o an antibody. Te container is hinged on one end and sealed with a chemical lock at the other. On the exterior there is an aptamer, a molecule that recognizes the surace o a particular kind o cancer cell. When recognition occurs, the chemical lock at the ront o the container receives a signal to dissolve, and then the device opens up. Te two molecular payloads make contact with the cancer cell and penetrate it, whereupon they send a signal rom its interior or it to initiate its own death.Douglas and colleagues used their nanobot on a species o lymphoma and a species o leukemia cell, with positive results both times. Other cancers would need other customized aptamers. Tis is the irony and the glory o nanotechnology: i one knows what a molecule does, and it does so consistently in the right conditions, then devices measured in nanometres can do things that gadgets measured in micrometres cannot. Furthermore, the molecular devices can operate autonomously without needing either impossibly small on-board computers or external controls. And this brings to mind a major ault-line in thinking about building micro- and nanoscale devices. In top-down processes, a larger-scale machine is supposedly reduced, more or less intact, to a much smaller scale — the Proteus  or the nano-lice, or example. Bottom-up processes put together a limited number o molecules and unctionalize them, without their builders caring whether they resemble larger machines. Te Wyss-bots illustrate this latter approach.Tese nanobots, like their science fiction cousins, also have a caveat. Tey have been tested only in vitro . It will be wonderul i they were tested too in vivo , and with similar successul results. But it is a long distance between in vitro  tests and clinical trials with human subjects. I it is true that patience is a virtue, then one will need a great deal o that virtue between now and the day that clinical trials succeed.And yet the nanobots rom the Wyss Institute have already become celebrities. When the Obama administration announced its initiative to map the active human brain, in February 2013, its act sheet reerred vaguely to developments in nanoscience and to “molecular-scale probes” 6 . John Markoff, writing in the New York Times , gave a particular example, namely, the nanobots rom the Wyss Institute (along with a mention o the Proteus ) 7 . How will these cancer-killers serve the mission o mapping brain activity? How will we get rom oncology to neurology via the devices rom Wyss?I asked Markoff about this, and he told me that he reerred to the Wyss nanobots as an example o the state o the art: not exactly to say that the brain mapping initiative is going to enlist the Wyss cancer killers today or tomorrow, but rather that nanoscience can soon deliver nanoscale devices or a variety o diagnostic and therapeutic tasks (J. Markoff, personal communication). Te brain activity mapping project will benefit rom the things that nanoscience can do now and in the years ahead.I agree, and I note that multiple nanoscale medical devices are currently in clinical trials 8 .So this is the biography o the nanobots: first there were various miniaturization stories in science fiction, including Fantastic Voyage ; then nanotechnology caught the attention o another generation o sci-fi writers and illustrators; afer that there were many lovely pictures o nanobots in the media, but then they became passé; and meanwhile, molecular devices are being developed to fight cancer cells and other evil things. Not as sexy as the Proteus  perhaps, but still totally cool i they work in vivo . ❐   Chris Toumey is at the University of South Carolina NanoCenter. e-mail: Toumey@mailbox.sc.edu  References 1. Lynn, S. in Encyclopaedia of Nanoscience and Society Vol. 2 (ed. Guston, D.) 700–701 (Sage, 2010).2. Nerlich, B. Science as Culture   17,  269–292 (2008).3. Lösch, A. Yearbook of Nanotechnology in Society Vol. 1 (eds Fischer, E. et al. ) 123–142 (Springer, 2008).4. oumey, C. & Cobb, M. Leonardo   45,  461–465 (2012).5. Douglas, S., Bachelet, I. & Church, G. Science   335,  831–834 (2012).6. http://www.whitehouse.gov/the-press-office/2013/04/02/ act-sheet-brain-initiative7. Markoff, J. New York Times  D1, D6 (26 February 2013). 8. Service, R. Science   330,  314–315 (2010). © 2013 Macmillan Publishers Limited. All rights reserved

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