February 2006 Archives

Paul Boutin has posted a story on his blog, "Biowar for Dummies,"  originally written for Wired Magazine but never published.  I'll take this opportunity to correct two small points before the story is widely read.

1.  The Molecular Sciences Institute is a non-profit research institute, not "a California biotech firm".  It was founded by Sydney Brenner in 1996.  I was a Research Fellow there from 1997 to 2002.
2.  I am most emphatically not designing, nor building, new organisms in my home.  I am, however, designing new proteins.  I would prefer local and federal authorities not get confused about this.

Here is a link to the original paper with the "Carlson Curves", "The Pace and Proliferation of Biological Technologies," published in Biosecurity and Bioterrorism in 2003.  There is more of my writing on the subject at www.synthesis.cc.

Reuters (via the NY Times) is reporting that H5N1 has been confirmed in poultry and people in India, and appears to be the cause of death of ducks in France.  Check that -- the radio news just said H5N1 is confirmed in France.  No print/web confirmation yet that I see.

These results may be consistent with the notion of H5N1 being spread both through migratory birds and through domesticated poultry, presumably with poultry being transported across borders, often illegally.  This debate is ongoing at ProMED.  Some quick checking by Todd Harrington at bio-era suggests the flow of poultry from China and Turkey to Nigeria isn't as promiscuous as claimed by the recent Washington Post article, and it seems all legal poultry exports from China are now as cooked meat.  All legal exports, mind you, from a country with absurdly long borders.  All this is just more cause for concern and confusion, it seems.

Alas, even the best informed people are having trouble figuring this out.

The Washington Post is reporting that, "The lethal strain of H5N1 bird flu found in Nigeria this month probably got there in poultry and not through the movement of wild birds." 

The article, by David Brown, quotes Billy Karesh of the Wildlife Conservation Society in New York, with whom I collaborate through Bio Economic Research Associates:

I would never rule out wild birds. But I think we have to look at the most probable routes, and the most probable route would be poultry. How did it skip the whole Nile Delta and get to Nigeria? That kind of bothers me. Common sense would dictate that it should be all over Egypt by now.

Though I've been skeptical about transmission via traveling poultry, I can't argue with Dr. Karesh's reasoning.  Mr. Brown also writes that:

The first Nigerian cases were found at a commercial farm with 46,000 chickens, not among backyard flocks that would have greater contact with wild birds. Nigeria imports more than a million chicks a year from countries that include Turkey, where H5N1 appeared last fall, and China, where it has circulated for a decade.

So there is at least trade in poultry from Asia towards Nigeria, and perhaps also from Asia towards Turkey, though I am still checking into the latter possibility.  But even if shipping of poultry turns out to explain the appearance of the virus in Turkey, it seems to be showing up in wild birds first in other countries, for example last week in Italy, Greece, and Bulgaria, and just this week in Germany, Austria, and Iran.

Which leads me to think we will see the virus all over Western Europe in a matter of weeks.  Of course, nobody still has any idea how this is going to turn out in the long run.

Liftport announced Monday the results of a January test of a 1-mile long ribbon, with robots climbing and descending a portion of the distance.  Evidently, technical issues limited the performance of the climbers, which had performed well in tests.  The New Scientist is carrying a short article as well.

In other news, the Liftport Book is now available from Amazon.com.

Bio.com is reporting -- okay, more like carrying a press release -- that Healtheuniverse, Inc., is preparing for clinical trials of stem cells recovered from human fat tissue.  Quoting from the document in question:

Scientific protocols are being prepared for the first human clinical trials using the company's proprietary stem cell technology. This technology uses adipose tissue, or fat which can be used as an abundant source of stem cells for tissue engineering and regenerative medicine. The Company intends to sell this proprietary technology to physicians, clinicians and medical organizations through a packaged product line and licensing agreements within the worldwide regenerative medicine market which is estimated to grow to $500 billion by 2010.

First, clinical trials for regenerative medicine are just getting underway, which means that in only 4 years we are very unlikely to see a $500 billion market.  Second, Healtheuniverse?  HEALTHeUNIVERSE (Ticker: HLUN.PK), according to the website.  A stylism that bears an uncomfortable similarity to www.healthEuniverse.com, and looks like it was suggested by the namebots at Network Solutions.  Brings back nightmares from, say, circa 1999.  But then they are in Biopolis, Singapore, so perhaps I should forgive the name.

All fun derived from the name aside, the technology in general shows great promise.  Zuk, et al., published a paper in Molecular Biology of the Cell in 2002 (full text at PubMed) showing that, "Human adipose tissue is a source of multipotent stem cells."  This may be a way to generate therapeutic patient specific stem cells from adult tissue without cloning.  For example, Timper, et al,. published just last month (PubMed) an article demonstrating, "Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells."

So, promising, and still off in the future.  But I don't think a company trading on the Pink Sheets will be my first stop for stem cell therapy.

Jamais Cascio over at WorldChanging points to a short report on Non-GM Biotech for the Developing World.  Focusing mostly on breeding techniques and molecular diagnositics, the brief suggests policy makers should be thinking more clearly about the benefits of technology beyond genetic manipulation.  I definitely agree, and the topic deserves considerably more attention than it is presently getting.  One could, say, write a whole book about the full range of biological technologies and their potential.  I suppose I should get a move on.

The New York Times is reporting today that, "Bird Flu Detected in Swans in Italy, Greece and Bulgaria."  It seems that only very preliminary testing has been done so far, but enough to identify H5N1 as the cause of death in at least some wild birds found in the past few days.  The article notes that the virus was roughly identified via rapid screening:

In Italy, police officers near Messina, in Sicily, found two dead swans on Thursday and performed rapid screening tests on them in the wild, which suggested that the swans had a flu virus, according to ANSA, the official Italian news agency.

I find this surprising and impressive.  The cops in Italy are equipped and trained for biosecurity work?  And what tests are they using?  ELISA?  PCR?  Something more like a pregnancy test?  Does anybody reading this know the details?  Were the tests actually performed by beat cops, or were specially trained technicians brought in when the birds were found?  Perhaps this is an indication of how well prepared the Italians are to host the Olympics. 

No sign of the virus in domestic poultry yet.  This would be consistent with the notion that the virus is in fact spread by migrating birds rather than by human travel and trade, a dispute that I addressed when H5N1 showed up in Turkey.

The study of RNA interference and its therapeutic application are moving so fast I have almost given up trying to keep on top of it.  But we should all pay more attention, because it appears that inhaled siRNA (short interfering RNA) may be an excellent rapid-response technology for disease outbreak situations. 

(Update 7 Feb 06.  Here are a couple of readable primers on siRNA from Answers.com and Wikipedia.)

Previous work has shown inhibition of flu viruses in cell culture and in mice using siRNA.  The experiments in cell culture are nice for demonstrating basic biology, and the work in mice demonstrates physiological effectiveness, but both are a long way from showing anything safely works in humans.   This is particularly true of the work in mice, because compounds are often delivered via a massive injection into a tail vein, which you just can't do in humans.

A paper in the January 2005 edition of Nature Medicine (PubMed) demonstrated inhibition of two negative stranded RNA viruses via nasal administration of siRNA in mice.  Still in mice, but the authors are confident that the results show the technique is amenable to use with nasal inhalers in humans.  Yes, you will probably sneeze immediately, but you will also probably be protected from the flu.

Bitko, et al., start off by noting that:

Viral infection of the respiratory tract is the most common cause of infantile hospitalization in the developed world with an estimated 91,000 annual admissions in the US at a cost of $300 million. [Respiratory syncytial virus (RSV)] and [parainfluenza virus (PIV)] are two major agents of respiratory illness; together, they infect the upper and lower respiratory tracts, leading to croup, pneumonia and bronchiolitis. RSV alone infects essentially all children within the first two years of life and is also a significant cause of morbidity and mortality in the elderly. Infants experiencing RSV bronchiolitis are more likely to develop wheezing and asthma later in life. Research towards effective treatment and a vaccine against RSV has been ongoing for nearly four decades with few successes. Currently, no vaccine is clinically approved for either RSV or PIV. Strains of both viruses also exist for nonhuman animals, causing loss to agriculture and the dairy and meat industries.

In short, respiratory viruses cause considerable disease and death, even in Western countries, and have an economic impact upwards of half a billion dollars per year in the US.  Probably considerably more, if you start adding up productivity losses in the workplace.

After demonstrating previously that siRNA is efficient an antiviral in cell culture, Bitko, et al., set out to test the technology in mice.  Here is where it gets really interesting: They used a free, web based algorithm from the Whitehead Institute to choose the sequences for their RNAs (follow the "about" link to see an explanation of design guidelines).  The rules for designing siRNA are still being worked out, as evidenced by the fact that the best sequence experimentally was, "not suggested by several design engines, including those of Whitehead and Dharmacon, indicating the need for experimental verification of siRNAs."  Not so surprising, given the novelty of the technology.  But I'm fascinated by the fact that anyone could choose a sequence they want to inhibit and have access to design tools.  And the tools will get much better, probably fairly quickly.

Following the design stage, RNA was chemically synthesized, presumably by Dharmacon, who produced RNA for the earlier paper.  Rather than listing absolutely all the details of this work, here are the highlights:

• The RNA was administered nasally, with and without being complexed with transfection reagent TransIT-TKO.
• Mice were challenged with virus 4 hours later and then monitored.
• siRNA reduced viral titer by as much as 99.98%.  The authors estimate that the transfection reagent free siRNA "was 70-80% as effective as siRNA complexed with TransIT-TKO."
• Mixed siRNA was effective against challenge with multiple viruses.
• siRNA was effective as a treatment after infection; "[Mice] receiving siRNA at subsequent days (day 2-4) showed gradually less and less protection, although we still observed substantial improvement of weight."

The authors sum up:

The principal finding of this paper is that appropriately designed siRNAs, applied intranasally, offer protection from respiratory infection, as well as providing considerable therapeutic value when administered after infection. We suggest that siRNAs, delivered by small particle aerosols in a simple hand-held inhaler, might prevent or cure pulmonary infections in humans.

I'll continue to post on this topic as I learn more.