Here's to Happy Holidays and a Prosperous New Year

Merry Christmas, Happy Hannukah, or whatever it is you celebrate (or not). May your nanotech investments result in very macro profits in 2006. And may you and your family remain healthy and happy.

Silver: The Once and Future Antimicrobial

A few years ago, a friend of mine named Randy received a nasty gash on his leg while helping with a rescue on Tennessee’s Ocoee River, a favorite play spot for whitewater enthusiasts. Randy was immediately taken to a local emergency room where his leg was stitched up and he was given a prescription for antibiotics. That should have been the end of the story.

A few weeks later Randy's fiancé received a message that Randy (who lived in another state) had been hospitalized. Concerned, she phoned his doctor, who said, “We’re pretty sure now that he’s going to make it, but we’re not sure we can save the leg.” Randy’s wound had become infected with a multiple drug resistant (MDR) bacteria. It is pretty certain that this bacteria came not from the less-than-pristine waters of the Ocoee, but from the hospital where he was treated. The wonder of modern medicine in the 21st century is that every routine visit to a hospital is a lottery in which you might become infected with a life-threatening pathogen. Infections like Randy’s cause 90,000 deaths in the U.S. per year, more than twice the number of AIDS deaths, according to the CDC. In this case, although Randy had a rough time of it, the story had a happy ending; the leg was saved and the happy couple got married.

MDR bacteria are a real time example of evolution in action. The minute the FDA approves a new antibiotic, the bacteria start evolving a way around it. With a doubling time of 20 minutes to an hour, bacteria can evolve faster than the pharmaceutical company’s product cycle, which is realistically about 12 years between innovation and FDA approval. MDR bacteria tend to hang around hospitals, where the use of antibiotics is the highest, although episodes of community-acquired infection are increasing.

In the last week, the FDA approved an old drug, an antibacterial called silver, the same precious metallic stuff that earrings and bracelets are made of. The FDA approval consisted of Silver Soaker catheters from I-Flow, which use AcryMed’s “silver nanotechnology that can render existing medical devices impervious to infection-causing bacteria”. The catheters are coated with silver nanoparticles that kill most bacteria, even those that are resistant to the most advanced antibiotics.

Silver helps heal wounds; this little sliver of information has been common knowledge in the medical profession since the ancient Greeks, long before the germ theory was formulated. Bulk silver, however, doesn’t dissolve well, so its efficacy as an antimicrobial has been marginal at best. Thus it has largely been displaced by modern antibiotics.

Antibiotics are cleverly designed molecules that interfere with a microbe’s biochemistry, usually at a single site. Silver, by contrast, is a blunt instrument that interferes in several different ways with a bug’s life style. As a result, it is difficult for a bacterium to develop resistance. Silver is able to kill vancomycin and methicillin resistant pathogens, which have spilled out from hospitals into the community in recent years to become a major problem.

Nanocrystalline silver is a textbook example of the difference in behavior between nanophase material and bulk material. The antimicrobial action of highly disordered nanocrystalline silver occurs more rapidly (in as little as 30 minutes) and lasts longer than bulk silver particles.

Nucryst Pharmaceutical produces Acticoat, a dressing for serious burns that is impregnated with nanocrystalline silver. The product replaces a generic silver-containing cream that was only active for a few hours, after which it had to be scraped off (at considerable cost in agony to the burn patient) and reapplied. Acticoat, on the other hand, is good for a week and can be lifted off in one piece. Acticoat is now also FDA approved for use with serious wounds, including diabetic ulcers. These wounds, which usually form on the feet or limbs, can require amputation if the wounds do not heal. Acticoat was named one of the top ten nanotech products for 2004 (even though it was introduced in 1998) by the Forbes Wolf/Nanotech report. Though manufactured entirely by Nucryst, Acticoat is marketed by health science giant Smith and Nephew. The product has allowed Nucryst to score modest profits in 2003 and 2004.

The success of Acticoat in healing recalcitrant wounds led researchers to speculate that an antimicrobial action was not the whole story. Sure enough, it turns out that nanocrystalline silver has an anti-inflammatory action as well—specifically, it suppresses the activity of two inflammatory cytokines, interleukin 12B, and tumor necrosis factor alpha. Therefore Nucryst is exploring use its use in inflammatory conditions, including atopic dermatitis and certain respiratory conditions.

Nucryst is a subsidiary of Westaim Corporation [NASDAQ—WEDX; TSX—WED].

Who Knows Nano?

Those who work in the field of nanoscale science and nanotechnology tend to believe that the world shares their obsession. Believe me, nothing could be further from the truth.

My book, The Nanotech Pioneers, relates the story of a survey that a fellow journalist and I conducted in a bar in Columbia, South Carolina to determine how many people there had actually heard the term “nanotechnology” before. We found one patron, an aerospace engineer, who knew what we were talking about.

More recently, a more scientific survey of 700 Americans has been done by Dietram Scheufele, (University of Wisconsin-Madison) and Bruce Lewenstein (Cornell University). They found (surprise, surprise) that Americans know little about nanotechnology. Less than half knew the difference between a nanometer and an atom, which doesn’t say much for scientific education in this country. Of those who had heard of nanotechnology, most were positively disposed toward it. Those that were negative toward nanotech cited previous controversies concerning genetic engineering and stem cell research.

Another survey was done by two media experts for a report sponsored by Wilson Center's Project on Emerging Nanotechnologies. “The most notable characteristic of media coverage of nanotechnology is the lack of it,” said Andrew Laing, president of Cormex Research. The findings were drawn from a 2004 survey of top U.S. and Canadian newspapers. They discovered that American and Canadian newspapers print, on average, about one nanotechnology article of substance per month.

Yet another study by Sharon Friedman of Lehigh University illuminates another problem. The study focused on U.S. or British articles about health effects or environmental risks of nanotechnology, as reported in the Lexis/Nexus database. “While in both countries, news stories were overall balanced, article headlines were not,” said Friedman. “Close to half of them were negative: 48 percent in the U.S. and 44 percent of the U.K. articles.” Which is a real problem, since most people don’t actually go as far as reading the articles.

What should be done? Maybe the nanotech industry should take a page from the Pentagon’s play book and hire the Lincoln Group to place pre-paid positive articles into the news media. For a small fraction of the $100 million paid by the Pentagon I would gladly participate.

The EPA Gets Its Act Together

The Environmental Protection Agency (EPA) has released a Nanotechnology White Paper for external review. They should be commended as they have come a long way in a short time period. The following paragraphs, about a meeting held a couple of years ago, were adapted from my book, The Nanotech Pioneers: Where are they taking us?

I was fortunate enough to be present at an informational meeting held in Washington between nanotech industry trade group leaders and representatives of the U.S. Environmental Protection Agency (EPA) and the Food and Drug Administration held in 2003. The meeting was held as an exchange of ideas about what challenges the nascent nanotechnology industry might present to regulators. The presentation of the EPA was illustrative of the problems that the EPA faces with nanomaterials. For instance, certain chemicals it considers hazardous require special care in handling, transportation, storage and disposal. The EPA categorizes chemicals, naturally, on the basis of their chemical formula. But consider the problem of carbon nanotubes. To the EPA in 2003, a carbon nanotube was just carbon, the same as graphite, the same as diamonds, the same as carbon black (colloidal carbon). There was no special care required in handling carbon nanotubes at that time, and for that matter, as virtually no toxicology had been performed, nobody knew whether nanotubes were dangerous or not.

The EPA representative did his best to reassure the nanotech leaders that his agency was not about to do anything to stifle the growing nanotech industry. On the other hand, trade group leaders, particularly Bo Varga of NanoSIG, argued vociferously that the EPA should indeed step in with serious regulation.

The expected roles were reversed—the regulators not wanting to regulate while the potential regulatees were demanding it. How to explain this weird discrepancy? Beyond the talk of “grey goo” and the public’s reaction to the inevitable movie version of Michael Crichton’s novel Prey, there were real concerns:

1) The uproar over genetically-modified organisms (GMO) or “Frankenfoods” has convinced high tech industry in general that public relations are important. One of the spinners of the Frankenfoods controversy, the radical environmentalist organization RAFI (Rural Advancement Foundation International) has been reborn as Etc Group and has nanotech in its sights. They have released a couple of very negative reports on what they call Atomtech.

2) People in the industry recognize that some nanoparticles, eg carbon nanotubes, could have real health risks similar to asbestos in an unregulated environment. The first “Love Canal” type environmental episode might have a seriously detrimental effect on the nanotech industry as a whole.

Nanomaterials can easily generate adverse consequences if they enter the human body. Looking from a biological perspective, on first principles, one can see, for instance, that carbon nanotubes would be very hydrophobic and therefore difficult to eliminate from the body. The extremely small diameter suggests that they could easily penetrate cells (which in fact, they do). Carbon nanotubes are also physically just about indestructible and unlikely to be easily biodegraded. Carbon nanotubes also have a tendency to aggregate and therefore there is a high probability that they would tend to collect in the lungs and perhaps in the nephrons of the kidney. But until recently, nobody had done any real toxicology on carbon nanotubes.

The EPA’s white paper suggests that they are now taking the problem seriously:

A search of the literature on particle toxicity studies published up to 2005 confirms the paucity of data describing the toxicity of chemically defined ultrafine particles and to an even greater extent that of intentionally produced nanomaterials, The ability to assess the toxicity of intentionally produced nanomaterials by extrapolating from the current particle toxicological database was examined by Lam et al. (2004) and Warheit et al. (2004). Their findings demonstrate that graphite is not an appropriate safety reference standard for carbon nanotubes [No kidding!], since carbon nanotubes displayed very different mass-based dose-response relationships and lung histopathology when directly compared with graphite.

Studies conducted by Lam et al. (2004) and Warheit et al. (2004) examining the pulmonary toxicity of carbon nanotubes, have provided evidence that intentionally produced nanomaterials can display unique toxicity that cannot be explained by differences in particle size alone. For example, Lam reported single walled carbon nanotubes displayed greater pulmonary toxicity than carbon black nanoparticles. Similar results have been obtained from comparative in vitro cytotoxicity studies (Jia et al.,2005). Muller et al. (2005) reported multi-walled carbon nanotubes to be more proinflammatory and profibrogenic when compared to ultrafine carbon black particles on an equivalent mass dose metric. Shvedova et al. (2005) reported unusual inflammatory and fibrogenic pulmonary responses to specific nanomaterials, suggesting that they may injure the lung by new mechanisms.

Which is not to say that carbon nanotubes or other nanomaterials should not be developed. But if I worked in a factory where they were produced, I would want to be assured that procedures were in place to make sure that nanomaterials didn’t become aerosolized. Reasonable precautions should not, and so far, have not been resisted by the industry.

Mea Culpa, Again

O.K., I really screwed up. Jonathan Depres had complained about a post in which I described the cryonics solution used at Alcor to vitrify human bodies as a mixture of “polyethylene glycol, formic acid, dimethyl-sulfoxide and glycerol." This was the impression I had mistakenly received from a talk by Brian Wowk of 21st Century Medicine and a discussion afterwards at an Immortality Institute conference. Subsequently, I received an e-mail from the same Brian Wowk telling me I had got it wrong.

“There is no formic acid, polyethylene glycol or glycerol in M22. Since formic acid is highly poisonous, this claim is borderline defammatory,” said he. M22 contains formamide, not formic acid; ethylene glycol not polyethylene glycol; and whereas glycerol is sometimes used for cryopreservation, it is not a component of M22 at all.

I apologize to Dr. Wowk, to 21st Century medicine, to Alcor and to Jonathan Depres. For the record, here is the recipe for M22, as recorded in a paper on which Brian Wowk is a co-author.

Components of M22

Dimethyl Sulfoxide, 2.855 M
Formamide, 2.855 M
Ethylene glycol, 2.713 M
N-Methlyformamide, .0508 M
PVP K12, .0056 M
PVA, .005 M
PGL, .0267 M5 LM5, 20 ml/dl

Nanotech-Enabled Evolution of the Cell Phone

I used to tell my wife that I would be the last person in America to own a cell phone. I don’t like talking on the phone at all and don’t feel the need to be connected 24/7 to all the people that might want to talk to me. But I’m obviously in the minority.

Of course cell phones are not just phones anymore. Cell phones are evolving into complicated devices that may include the functions of a phone, a watch, a digital assistant, an MP3 player, a game player, a calculator, an internet access device, camera, an audio recorder and a credit card. Kids seem to have them implanted in their ear during their teen years as the first step toward their eventual transformation into full-time cyborgs.

The key to stuffing ever more functionality into something that must be pocket-sized is miniaturization of the individual components. And that’s one reason cell phone companies are interested in nanotechnology.

Jim O’Conner is a Motorola vice-president in charge of that company’s Early Stage Accelerator (ESA), a kind of in-company incubator for new technologies. Developing high tech in big companies is a cumbersome project involving a lot more bureaucracy than you would get in your average five person start-up. Since Motorola jettisoned its semiconductor division, the company is all about phones, so any new technology that the ESA considers must relate in some way to that all-important product.

How can nanotech improve the cell phone? O’Conner lists the following aspects of a cell phone where nanotech may play a role in its evolution:

Antennas
Acoustics
Coatings
Displays
Coatings
Paints
Batteries
Sensors/Actuators

That doesn’t seem to leave much out, does it? Nanomaterials and coatings will make cell phones cases stronger and more durable. Prototypes of carbon nanotube-based emissive displays have already been constructed. Nanotubes are also being used by Motorola to create a micro-fuel cell to replace batteries. MPhase Electronics is working with Bell Labs on a battery that uses silicon nanotubes. Nanotube transistors have also been used experimentally to make very sensitive antennas.

To O’Conner’s list one could also add polymer LEDS made with thin-film technology, which have already found their way into displays in consumer electronic devices. Adding functionality to the cell phone will also require the development of denser nonvolatile memories, which could be spintronic MRAM, nanotube-based NRAM or nanocrystalline silicon memories.

Comments, Errata, Odds and Ends

Hopefully, we will eventually have a forum associated with this blog or at least a way for readers to attach comments to various posts. In the meantime, I will periodically try to respond to e-mails. If you have comments, send them to steven.alan.edwards@gmail.com.

Patent fight?

Cedric Loiret-Bernal, CEO of NanoInk, objects that Bioforce Nanosciences should not have been mentioned in the post Writing very,very small about dip pen nanolithography. NanoInk has an exclusive license with Northwestern for this process and the term “dip-pen nanolithography” has been trademarked by NanoInk.

Both companies make systems, more or less based on the atomic force microscope, in order to print in small spaces with molecular ink. Bioforce makes a “Nanoarrayer” that is able to shrink the area used for biological “microarrays” by a factor of 10,000. The Nanoarrayer is optimized for making dots quickly, whereas NanoInk’s Nscriptor system is a more general purpose machine—it can make lines and even letters

Does NanoInk’s exclusive license portend a patent fight between the two companies? Not until Bioforce makes enough revenue to share between the lawyers would be my guess.

Thank you, Wikipedia

Jonathan Depres, apparently from Alcor, complains that I have confused the terms cryogenics and cryonics in my post on Immortality, Nanotech and Magic.

According to Wikipedia:

Cryogenics is the study of very low temperatures or the production of same and is often confused with cryobiology, the study of the effect of low temperatures on organisms or the study of cryopreservation. Likewise, cryonics is the nascent study of the cryopreservation of the human body. Unlike cryogenics, cryonics is not an established science and is viewed with skepticism by most scientists and doctors today.

Mea culpa. I will go back and edit the post.

Jonathan also complains about my description of the Alcor’s cryo-preservative as a mixture of “polyethylene glycol (automotive antifreeze) formic acid, dimethyl sulfoxide and glycerol." He says that they use M22, a new cryoprotectant invented by 21st Century Medicine for the preservation of small organs like corneas and the meniscus of the knee. I specifically asked Brian Wowk, Senior Scientist at 21st Century Medicine what M22 was composed of, and he said “polyethylene glycol, formic acid, dimethyl-sulfoxide and glycerol.” [This is in error, corrected in a later post. Actually, M22 contains ethylene glycol, formamide, and dimethyl-sulfoxide but no glycerol.]

On the Lux Research/Powershares exchange traded fund

Cientifiica comments on my previous post, Nano and Not-so-Nano. “We actually agree with Steve that most of these so called 'nano' [in the Hardly Any Nano category] companies derive little of their income from anything nano related, or ever will,” they say.

Von Ehr Interview

Nanotechnology.com has posted my interview with Jim Von Ehr, CEO and founder of Zyvex. In it, Von Ehr talks about his reasons for starting the company, carbon nanotubes in baseball bats, nanomanipulators, MEMs-based miniaturized electron microscopes, atomically precise manufacturing, his investment in Atomate, and nanotech solutions for energy. A preview of the interview has been given in a previous post, Of Nanotech Dreams and Revenue Streams.

RSS Feed

I have been asked if I will send out e-mails of my posts. I can't do that. However, there is an RSS (really simple syndication) feed. Just paste the following into your RSS aggregator, http://www.nanotechnology.com/blogs/steveedwards/atom.xml. That way you will know when the page has been updated.

Nano and Not-so-Nano

I have finally gotten around to looking into the composition of Lux Research’s “nanotechnology” Exchange-Traded Fund [AMEX: PXN], which began trading November 1st. First, let me say that I sympathize with anyone trying to dream up a nanotech index. It is not easy, because there are not that many publicly-traded nanotech companies. Some of the better nanotech companies, like Zyvex and Nanosys, have yet to hold an IPO. Also, I do not get into religious arguments about what constitutes nanotech. There is a continuum stretching from submicron to subatomic and nobody is going to hobble his business enterprise by a strict adherence to a portion of the scale. Still, my first reaction to viewing the Powershares Lux Nanotech Portfolio is: YOU HAVE GOT TO BE KIDDING!

The idea of an exchange-traded fund, I thought, was to track a segment of the market on an industry-basis, like the semiconductor companies or the biotech companies. PXN tracks the Lux Nanotech Index which according to CEO Peter Hebert “is designed to serve as a benchmark for the value that markets ascribe to emerging nanotechnology.” Seriously, would you buy General Motors as an example of “emerging nanotechnology?” PXN is a hodgepodge of stuff, which if you’re lucky might track the general market.

Many of the names in the index are so well-known that no knowledgeable investor could delude himself into thinking that a significant proportion of their revenues derive from nanotech. Indeed, you would need a nanoscope to find an activity within some of these companies that relates to nanotech. But many are less well known. So below, I have parsed the PXN into precise categories based on the percentage of their revenues or activity that is related to nanotech.


Hardly Any Nanotech

Headwaters
Hewlett-Packard
BASF
IBM
NEC Corp.
General Electric
General Motors Corp.
3M Company
Air Products & Chemicals
Du Pont De Nemours

Some Nanotech

Elan (drug delivery technology)
American Pharmaceutical Partners (Abraxane, a cancer drug)
Westaim (nanocrystalline silver as antimicrobial)
Accelrys (molecular modeling)
Skye Pharma (drug delivery technology)
Biosante Pharmaceuticals (drug delivery technology)
Symyx Technologies (combinatorial chemistry)
Cambridge Display Technologies (polymer LEDS)
Flamel Technologies SA (drug delivery technology)
FEI Company (electron microscopes)
Veeco (scanning probe microscopes)
Immunicon (ferrofluids used for cell sorting)

Mostly Nanotech

Altair Nanotechnologies (nanoparticles)
Harris and Harris Group (venture capital focused on nanotech)
Nanophase Technologies (nanoparticles)
NVE Corp. (spintronics)


To be fair, some of the “Hardly Any” companies mentioned above, like IBM (see my recent post), have developed interesting nanotechnologies, Headwaters has developed some nanoscale catalysts for the energy industry that may find wide application. On the other hand, Headwaters already has a billion dollars in revenue involving stuff like building materials and coal-based fuel. I don’t know how General Motors uses nanotech and I don’t really care. The company is on the bankruptcy watch.

Hopefully, I will get a rebuttal of this post from Lux Research, which I will share with you when it comes.

A Better Proxy

Meanwhile, if you want a real proxy investment for the nanotech industry (I’m not saying you should; this is not a buy recommendation), consider Harris & Harris [NASDAQ: TINY]. H&H is a publicly traded venture capital company that focuses on what it calls “tiny technology”; not strictly nanotech but close enough. Yesterday, it announced that it had sold its stake in its last non-tiny technology company, Neurometrix [NASDAQ: NURO] for proceeds of $34.5 million. When H&H discovered Neurometrix, it consisted of a single person with an idea, Shai Gozani, a Harvard MD. Their investment has paid off many-fold.

The H&H portfolio contains some of the most interesting names in nanotech, including Nanosys (nanowires and quantum dots), Nantero (nanotube based memory), and Molecular Imprints (nanolithography).