Nanotechnology, a hard pill to swallow whole

Nanotechnology, a hard pill to swallow whole

It is imperative to separate myth from reality in nanotechnology’s vision for medicine, to help decide how the technology can improve our lives without compromising our dignity and freedom.

By Mae-Wan Ho

Micro- is not nano-

IN August 2001, scientists from Osaka University unveiled the world’s tiniest sculptures, bulls the size of a single blood cell, made using lasers. That was a dramatic demonstration that techniques for miniaturising machines are feasible, perhaps ultimately down to the size of molecules that could fit inside cells.

Researchers from universities of Glasgow, Edinburgh and Strathclyde are working on robots about the size of a pill that, when swallowed, could measure temperature, acidity and oxygen concentration in the stomach, and the signals transmitted to an external receiver. Other researchers have developed a minute camera in a pill that can transmit pictures of all parts of the gut.

But these miniaturisations are still far from the molecular scale of nanometres (a billionth of a metre), and purists would not include those devices in the realm of nanotechnology. All the same, the possibilities are endless.

‘There is plenty of room at the bottom,’ so said quantum physicist Richard Feynman in an after-dinner speech in 1959 that inaugurated the age of miniaturisation that has led ineluctably towards nanotechnology.

The microbull-sculpting scientists in Osaka have also built the smallest micromechanical system ever, a spring whose arm is only 0.3 microns wide, which would just qualify as a nanodevice. (A micron is a millionth of a metre.)

Carlo Montemagno of Cornell University made a molecular motor less than one-fifth the size of a red blood cell. The key components are a protein from E. coli attached to a nickel spindle and propeller a few nanometres across, which is powered by ATP, the energy-intermediate that the body itself uses to power all living activities. But this molecular motor works with the efficiency of only 1 to 4%, comparing poorly with those in living organisms that could work at close to 100% efficiency.

Researchers in Michigan have designed smart ‘nanobombs’ that are said to evade the immune system, to home in on diseased cells to kill them or deliver drugs to them.

Also ‘on the way’ are electronic devices that can tell cells to make specific hormones when the body needs them, and electricity generators that ‘self-assemble’ inside the cell.

The first medical application of implantable nanotechnology was tried in diabetic rats. This implant, developed by Tejal Desai of the University of Illinois, consists of a silicon box a 10th of a millimetre across – too large to qualify as a nanodevice – containing a sponge of fibrous collagen tissue seeded with pancreatic cells from the pig, dog or mouse. The box is porous with holes 20nm wide that can let glucose molecules in. If the cells detect too much glucose in the bloodstream, they start producing insulin. The insulin molecule is small enough to pass through the pores into the bloodstream and bring the glucose level down. The hope is that bulky molecules such as antibodies won’t be able to get in to cause immune rejection of the cells in the box.

Another idea is to interact directly with cells, so they can be harnessed as pharmaceutical factories to produce drugs on demand. Milan Mrksich, chemist at the University of Chicago, plans to hook up cells to electronic circuits by tethering them to a carpet of molecular arms. Carbon chains between 10 and 20 atoms long attached to a gold-plated glass plate with sulphur atoms. The strands are packed so tightly that they have to stand upright on the surface. That creates a thicket of free sticky molecular ends to capture and manipulate cells.

To grab hold of cells, Mrksich can tag the exposed ends of the molecular chain with a ligand – a small molecule that binds to receptors on cells. When an electric potential is applied to the gold layer, electrons jump from the gold layer onto the molecule. Electron shift along the chain alters the chemistry of the ligand, activating it so that it will bind to a cell.

Different kinds of receptors on the cell surface, when stimulated by binding to specific ligands, can trigger the expression of different genes to produce different products. But will the tethered cells survive and do as they are directed? They may simply die when pinned onto electronic devices, or they will discard the receptor tethering them, and break free.

Although many potential uses are envisaged in biomedical applications, the actual products that will come on to the market for the foreseeable future are not much more than better research tools or aids to diagnosis. These include magnetic crystals and semiconductor crystals (quantum dots) attached to antibodies to detect the presence of specific protein antigens or bacteria, and nanoparticles for better drug delivery. In the pipeline are nanoshells used to kill cancer cells selectively avoiding complicated surgical intervention (see ‘Metal nanoshells, cure or curse?’ in this issue). But practically no safety data exist on any of these nanoparticles.

Nano-robots are science fiction

The much-hyped possibility of nanoscale robots – ‘nanobots’ – that can repair damaged cells, or self-replicate and run amok, as equally feared, remains in the realm of science fiction. Many scientists including Richard Smalley, 1996 Nobel laureate for ‘buckminster fullerene’, a new form of carbon in the shape of the geodesic domes designed by architect Buckminster Fuller, and George Whitesides, Professor of Chemistry in Harvard University, are both sceptical.

There are simply no working examples of molecular machines outside living cells, and those in living cells are made and assembled on totally different principles from the way chemists make them in the laboratory.

In the lab, one can use the atomic force microscope to pick up and move individual atoms; but that doesn’t mean one can make molecular-size machines that assemble other molecular machines. The atomic force microscope is a macroscopic device that can be precisely controlled to control individual atoms. Molecular size machines, on the other hand, will be subject to quantum forces that are basically uncontrollable. Another major problem is to supply the source of energy that can sustain the artificial molecular machines to do their work (see box ‘What’s wrong with Eric Drexler’s molecular machines?’).

Hype from reality and beyond

In contrast to the debate on genetic engineering, where misinformation, denial and obfuscation abound, scientists in this new area are informing the public with admirable clarity and candour, especially in separating hype from reality and in anticipating some of the risks involved (see special issue of Scientific American, September 2001).

As far as I can see, miniaturising diagnostic and surgical equipment, as in the pill-size monitors and cameras described earlier, are realisable possibilities that can deliver the benefit of minimising trauma and invasiveness of medical procedures.

The prospect of adverse immune reactions looms large, however. As David Williams, an adviser to the EU on problems of public perceptions of medical technologies, says, ‘The human body is best designed to repel or attack things the size of a cell.’ Worse yet, the devices could clog up our immune system for good.

Quantum dots, nanoparticles, carbon nanotubes (in microelectronics) and other throw-away nanodevices constitute whole new classes of non-biodegradable nano-junk and nano-smog, environmental pollutants that could make cancer-causing asbestos seem tame. The first safety tests on carbon nanotubes are indeed raising serious health concerns (see ‘Nanotubes highly toxic’ in this issue).

Other possible applications will raise immediate alarm. Nano-surveillance units could be swallowed, or injected and lodged in the body, so as to tag and keep track of individuals, even without their knowledge.

The spectre of nano-implants

‘Mind-control’ units could be implanted to make people behave in desired ways. The creation of a ‘roborat’ with implanted electrodes in the rat’s brain to make it move in controlled directions was reported in the journal Nature in May last year. This is a graphic demonstration of how implantable devices can compromise the most distinguishing hallmark of any organism, let alone a human being: the possession of autonomous purpose and will (see box ‘Roborat and implantable “mind-control”‘). There is no limit to the evil ends to which such technology could be put.

Nano-implants, even for seemingly benign purposes, have to be treated with scepticism and caution. The promises of implants that restore sight, hearing, speech, mobility, and other organ-functions are obviously beneficial to those who have lost those functions after birth, though others who were born without them might take a different view, and should not be coerced into accepting those devices. Even more scepticism and caution should be accorded to implants that are supposed to ‘enhance’ brain function, enable ‘brain to brain’ and ‘brain to machine’ communications (see ‘Nanotechnology, the wave of the future?’ in this issue).

Brain implants that allow humans to control electronic devices fill me with particular terror. Fine electrodes are inserted into hundreds of nerve cells in the brain, and cannot be removed without the help of a good brain surgeon. That’s bad enough. But far worse is the prospect of having to train oneself to repeat the same thought precisely for any given task so that the pattern of brain cell activities could remain the same or similar enough to be read by a robot. It is the thought that such a device will turn oneself into a true robot that’s really terrifying. It is almost as bad as being the roborat and having one’s brain controlled by another agent.

It is important for both scientists and the general public to keep close track of the developments, to distinguish hype from reality, and to decide how the technology can be safely used to improve our lives without compromising our dignity and freedom. u


1. ‘This bull is so small, it could sit on a single human blood cell. So what does this mean for medicine?’ by Richard Woods, The Sunday Times, 19 August 2001.
2. Scientific American Special Issue Nanotech, September 2001,
3. ‘Small visions, grand designs’ by Ian Sample, New Scientist, 6 October 2001, 31-7.
4. ‘Thanks, but no thanks’ by Michael Brooks, New Scientist, 6 October 2001, 33.
5. Talwar SK, XU S, Hawley ES, Weiss SA, Moxon DA and Chapin JK. ‘Behavioural neuroscience: rat navigation guided by remote control’. Nature 2002, 417, 37-8; also ‘Call them mouse-controlled rats’, Associated News article in Wired,1282,52236,00.html
6. ‘Machine-phase nanotechnology’ by K. Eric Drexler, Scientific American, September 2001.
7. ‘Controlling robots with the mind’ by MAL Nicolelis and JK Chapin, Scientific American, October 2002.


Box 1

What’s wrong with Eric Drexler’s molecular machines?

THE man who is said to have started nanotechnology is Eric Drexler, a space-systems researcher at MIT, who published Engines of Creation in 1986, in which he claimed that our ever-improving ability to manipulate matter would lead to the creation of machine parts the size of small molecules. Drexler was inspired by quantum physicist Richard Feynman, who gave an after-dinner talk in 1959 exploring the limits of miniaturisation, and ended up by arguing the possibility, even the inevitability, of ‘atom by atom’ construction.
Drexler foresees the creation of machine parts the size of small molecules. These could be assembled into machines much smaller than biological cells, which could interact directly with the machinery of biology. After all, he says, biology is nothing more than a bunch of molecular machines created and honed by evolution.

Drexler sees ‘molecular machines assemble molecular building blocks to form products, including new molecular machines’. It is the ultimate dream of the computer scientist to realise the self-reproducing automata, or in this case, the self-reproducing ‘nanobot’.
This alone caused much public alarm. So much so that Bill Joy, chief scientist of Sun Microsystems, wrote a long article in Wired magazine in 2000 proposing that we should consider stopping the developments of nanotechnology for fear of being overrun by a mass of ‘grey goo’ – self-replicating nanobots.

Drexler continues, ‘Stepping beyond the biological analogy, it would be a natural goal to be able to put every atom in a selected place (where it would serve as part of some active or structural component) with no extra molecules on the loose to jam the works. Such a system would not be liquid or gas, as no molecules would move randomly, nor would it be a solid, in which molecules are fixed in place. Instead this new machine-phase matter would exhibit the molecular movements seen today only in liquids and gases as well as the mechanical strength typically associated with solids. Its volume would be filled with active machinery.’

Drexler appears to be struggling towards the idea that the artificial molecular machines are like those of the living system, liquid crystalline with the texture of flesh. Living molecular machines in our bodies are made up of at least twice their weight of ‘biological’ water – water that is an integral part of their structure and function. These molecular machines, densely packed and embedded in the liquid crystalline matrix, run in almost perfect cycles, drawing on coherent energy extracted and stored from metabolism. The living molecular machines somehow manage to borrow the coherent energy and return it only slightly degraded to the matrix. The efficiency of living molecular machines is such that they generate very little waste heat, which is why they can be packed so densely and work without burning out.

One of the biggest problems for artificial molecular machines, let alone self-replicating molecular machines, is the energy source. Another is energy dissipation – to get rid of the waste heat – neither of which Drexler has addressed. But there is a deeper problem.

The organism is run, in the ideal, on quantum coherence. And hence – this is the sting in the tail – the molecular machines cannot be individually controlled. Instead, the organism is a system of molecular democracy of distributed control. Each individual molecular machine operates with maximum freedom and is yet correlated with the whole.

What about ‘the most exciting goal’ according to Drexler, ‘of the molecular repair of the human body’? Medical nanobots that could destroy viruses and cancer cells, repair damaged structure, remove accumulated wastes from the brain and ‘bring the body back to a state of youthful health’. Ah, the ultimate dream of immortality!

Unfortunately, our body’s immune system may well see these artificial molecular machines as foreign invaders and try to get rid of them, or worse, they might clog up the immune system for good.

If not, the non-destructible bodies would surely clog up the earth’s ecosystem for good.


Box 2

Roborat and implantable ‘mind-control’

A TEAM of scientists implanted electrodes in the rat’s brain to control its movements, treating it effectively as a robot, making it do things it would never do willingly on its own.

John Chapin, professor of physiology and pharmacology at the State University of New York in Brooklyn, who heads the team, envisages using the roborat, armed with a miniature camera, to search for survivors in collapsed buildings, for example. ‘There’s no robot that exists now that would be capable of going down into such a difficult terrain,’ he says.

Five rats have been implanted, each with three electrodes and a power-pack on the animal’s back. When signalled from a laptop computer, two of the electrodes stimulate the rat’s brain and cue it go to either right or left. The rat has had to be trained, and when it moves in the desired direction, it is rewarded by stimulation to a third electrode implanted in the ‘pleasure centre’ of the brain. When only the pleasure centre is stimulated, the rat goes straight ahead.

The rats’ movements can be controlled 1,600 feet away. After training, the rats could be remotely guided through pipes and across elevated runways. They could be compelled to climb trees and ladders and to jump from heights. The animals could even be commanded to venture into brightly lit, open areas that they would normally avoid.

It isn’t nanotechnology yet, and it is not new, though the principle of involuntary ‘mind-control’ through implantable devices is the same. Tiny video cameras could be strapped to the rats to transmit images and sounds of people trapped inside ruins.

The potential of using such implanted electrodes to control humans was investigated by a Tulane University researcher during the 1960s, with unclear results. That is something Chapin, the lead researcher, opposes so strongly he says it should be illegal.

But Kate Rears, a policy analyst at the Electronic Privacy Information Center in Washington, is worried that human-control technology can no longer be dismissed as far-fetched.

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