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Nanotechnology, a Hard Pill to Swallow

Dr. Mae-Wan Ho attempts to separate hype from reality in nanotechnology’s vision for medicine, to help decide how the technology can improve our lives without compromising our dignity and freedom.

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Micro- is not nano-

In August last year, 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 meter, and purists would not include those devices in the realm of nanotechnology. All the same, the possibilities seem 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 leads ineluctably towards nanotechnology.

The microbull-sculpting scientists in Osaka have also built the smallest micromechanical system ever, a spring whose arm is only 0.3microns wide, which would just quality 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 nanometers 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 percent, comparing poorly with those in living organisms that could work at close to 100 percent 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 University of Illinois, consists of a silicon box a tenth of a millimetre across – too large to qualify as a nanodevice - containing a sponge of fibrous collagen tissue seeded with pancreatic cells from 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 blood stream, they start producing insulin. The insulin molecule is small enough to pass through the pores into the bloodstream and bring 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 to 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 applications 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.

Nano-robots are science fiction

The much hyped possibility of nanoscale robots - ‘nanobot’ - 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 ‘buckminister fullerene’, a new form of carbon in the shape of the geodesic domes designed by architect Bucksminter 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. (My own critique of nanobots is contained in "Can computers become super-intelligent?", this series.)

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 published last September).

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.

But nano-implants have to 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 "The Brave New World quartet", this series).

The prospect of adverse immune reactions has already been pointed out. We have yet to develop artificial materials that don’t cause at least some problems when inserted into the body, starting with silicone breast implants. Nanoscale devices are worse. 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 may constitute whole new classes of non-biodegradable nano-junk and nano-smog, environmental pollutants that could make cancer-causing asbestos seem tame.

Other possible applications will raise 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.

‘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 this 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). There is no limit to the evil ends to which such technology could be put.

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 improve our lives without compromising our dignity and freedom.

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 labtop computer, two of the electrodes stimulate the rat’s brain and cue it either to go 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. Chapin’s team strapped tiny video cameras to the rats to see whether they might be used to transmit images and sounds of people trapped inside ruins. But Chapin says the camera needs to be refined to compensate for the rats’ jerky movements and the power backpack has to be miniaturized, for implanting beneath the skin.

According to a report in Wired magazine, Howard Eichenbaum, professor of psychology at Boston University, said the research may raise ethical concerns about turning animals into robots.

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 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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