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Nanobots todayNanobots have in the past been a fixture of science fiction writing and illustration, and such ideas are

now also appearing in scientific research. But, asChris Toumeyexplains, practical nanobots are different

from their science fiction counterparts.

Science fiction writers produced storieso miniaturized machines long beorethe prefix nano was crafed to mean abillionth o a metre (or a litre, or a gram,and so on)1. Te most amous o thesemachines was the Proteus, which appearedin the 1966 film Fantastic Voyage. Inthe film, a small submarine and its crewwere temporarily miniaturized or the

purpose o saving the lie o an importantscientist by entering his blood stream anddestroying a clot in his brain. Tis wasgood science fiction, especially the urgencyor the crew to exit the patients bodybeore they returned to normal size.

Some 20 years later, as nanotechnologycame to the attention o a new generationo science fiction writers and antasyillustrators, the theme o ultra-miniaturizeddevices blossomed again.

Tree kinds o nanobots (abbreviatedrom nano-robots) populated latter-dayscience fiction illustration. Te first was

a amily o machines with the abilities omechanical diggers that would excavateplaque and other nasty substances onthe inside suraces o our blood vessels.Te second was a group o submarine-like vessels that would locate viruses andother pathogens, and then destroy themwith lethal rays. Te third was the nano-louse, which had mechanical claws toseize a red blood cell and insert a needleinto it. Te pictures o nano-lice seemedespecially vivid in conveying the idea thatnanomedicine would soon have the abilityto cure diseases by using a remarkably

precise device.Brigitte Nerlich explains thatillustrations o nanobots were intendedto make nanoscale machines seem real,amiliar and beneficial2. Nanotechnologywould be acceptable to non-scientists ithey judged it in terms o these pictures.

And yet there was a puzzle in theportraits o the nano-lice. What exactlywere they doing? Once when I was leadinga discussion o nanotechnology with agroup o high-school students, we observeda picture o a nano-louse, and one o thestudents asked what operation it wasperorming. Some students thought the

needle was injecting a substance into thered blood cell; others said it was extractingsomething; a third group said it was doingneither, but merely grasping it firmly soit could move the cell rom one place toanother. Te answer, I said, was that it

was doing whatever the illustrator meantor it to do, even though we could nottell what the illustrator had in mind. Tisraises a good caution: it is not a good ideato create a picture o what nanomedicinecan do i it leaves the viewer wonderingwhat the device is doing, with three equallyplausible answers.

Another irony is that these supposednanobots are not nanoscale. I theywere real they would be measured inmicrometres, not nanometres. Tey areapproximately the size o one or two redblood cells, which are usually 5 to 10 min diameter. And although it is possible

to make moving parts at the scale omicrometres, there is no control system no on-board microcomputer smallenough to make each o them behave theway their illustrators suggest they would.And no such thing is on the horizon.

With or without these caveats,nanobots were especially prevalent in awindow o time rom about 1999 to 2001.Andreas Lsch explains that illustrationso nanobots in German media served asa device by which scientific, economicand mass media discourses could eachproject optimistic visions o the uture onanomedicine. Scientists were originallycomortable with these illustrations,says Lsch, but they later eared thenanobots had a weak reerence to currentdevelopments in nanomedicine3. Tiswas a polite way to say that scientistsdid not want to be held accountable or

A computer-generated illustration of a nano-louse attached to a red blood cell.

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the extravagant expectations o navenon-scientists.

In April 2010, Michael Cobbconducted survey-based research onpublic expectations or nanomedicine4.Interviewees read an optimistic articleabout nanomedicine; one group also saw a

picture o a nano-louse, which illustratedthe article, whereas the other group saw noillustration. In Cobbs words: Respondentswere slightly less supportive o nano ithey saw the image; Tey were also alittle a little less likely to report that itwould be beneficial; and Te imageappears to increase uncertainty amongthe uninormed.

So much or the idea that nanomedicineautomatically benefits rom pictureso nanobots.

Even though that idea is problematicand even misguided, there are other

devices at another scale, which are alsocalled nanobots, and their grounding inreality is more credible than the nano-lice. Molecular-scale devices (measuredin nanometres) are being built to target,penetrate and destroy cancer cells.

One good example is romShawn Douglas and colleagues at theWyss Institute at Harvard University whohave built a molecular-scale device toattack cancer cells, and to leave normalcells alone5. Tis is, in their words, anautonomous DNA robot capable otransporting molecular payloads to cells.

Te first step towards this device is anexercise in DNA origami, which is to saythat strands o DNA are linked to ormtwo-dimensional suraces, and thosesuraces can then be olded into three-dimensional shapes, including containersthat open and close. Inside an origamistructure are placed two molecularpayloads: a gold nanoshell o 5-nmdiameter and a ragment o an antibody.Te container is hinged on one end andsealed with a chemical lock at the other. Onthe exterior there is an aptamer, a moleculethat recognizes the surace o a particular

kind o cancer cell. When recognitionoccurs, the chemical lock at the ront o

the container receives a signal to dissolve,and then the device opens up. Te twomolecular payloads make contact with thecancer cell and penetrate it, whereuponthey send a signal rom its interior or it toinitiate its own death.

Douglas and colleagues used their

nanobot on a species o lymphoma anda species o leukemia cell, with positiveresults both times. Other cancers wouldneed other customized aptamers.

Tis is the irony and the glory onanotechnology: i one knows what amolecule does, and it does so consistentlyin the right conditions, then devicesmeasured in nanometres can do thingsthat gadgets measured in micrometrescannot. Furthermore, the moleculardevices can operate autonomously withoutneeding either impossibly small on-boardcomputers or external controls.

And this brings to mind a major ault-line in thinking about building micro- andnanoscale devices. In top-down processes,a larger-scale machine is supposedlyreduced, more or less intact, to a muchsmaller scale the Proteusor the nano-lice, or example. Bottom-up processes puttogether a limited number o molecules andunctionalize them, without their builderscaring whether they resemble largermachines. Te Wyss-bots illustrate thislatter approach.

Tese nanobots, like their science fictioncousins, also have a caveat. Tey have been

tested only in vitro. It will be wonderuli they were tested too in vivo, and withsimilar successul results. But it is a longdistance between in vitrotests and clinicaltrials with human subjects. I it is true thatpatience is a virtue, then one will need agreat deal o that virtue between now andthe day that clinical trials succeed.

And yet the nanobots rom the WyssInstitute have already become celebrities.When the Obama administrationannounced its initiative to map the activehuman brain, in February 2013, its actsheet reerred vaguely to developments

in nanoscience and to molecular-scale probes6. John Markoff, writing in

the New York Times, gave a particularexample, namely, the nanobots rom theWyss Institute (along with a mentiono the Proteus)7. How will these cancer-killers serve the mission o mapping brainactivity? How will we get rom oncology toneurology via the devices rom Wyss?

I asked Markoff about this, and he toldme that he reerred to the Wyss nanobotsas an example o the state o the art: notexactly to say that the brain mappinginitiative is going to enlist the Wyss cancerkillers today or tomorrow, but rather thatnanoscience can soon deliver nanoscaledevices or a variety o diagnostic andtherapeutic tasks (J. Markoff, personalcommunication). Te brain activitymapping project will benefit rom thethings that nanoscience can do now and inthe years ahead.

I agree, and I note that multiple

nanoscale medical devices are currently inclinical trials8.

So this is the biography o the nanobots:first there were various miniaturizationstories in science fiction, includingFantastic Voyage; then nanotechnologycaught the attention o another generationo sci-fi writers and illustrators; aferthat there were many lovely pictures onanobots in the media, but then theybecame pass; and meanwhile, moleculardevices are being developed to fight cancercells and other evil things. Not as sexy asthe Proteusperhaps, but still totally cool i

they work in vivo.

Chris Toumey is at the University of SouthCarolina NanoCenter.e-mail: Toumey@mailbox.sc.edu

References1. Lynn, S. in Encyclopaedia of Nanoscience and Society Vol. 2

(ed. Guston, D.) 700701 (Sage, 2010).

2. Nerlich, B. Science as Culture17,269292 (2008).

3. Lsch, A. Yearbook of Nanotechnology in Society Vol. 1

(eds Fischer, E. et al.) 123142 (Springer, 2008).

4. oumey, C. & Cobb, M. Leonardo45,461465 (2012).

5. Douglas, S., Bachelet, I. & Church, G. Science

335,831834 (2012).

6. http://www.whitehouse.gov/the-press-office/2013/04/02/

act-sheet-brain-initiative

7. Markoff, J. New York TimesD1, D6 (26 February 2013).8. Service, R. Science330,314315 (2010).

2013 Macmillan Publishers Limited. All rights reserved

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