And things continue to speed up. Several new technologies, including erasable electrostatic lithography, are bringing
practical quantum comouters a quantum step closer, for instance. Keeping up is a
problem for some, such as the U.S. Patent Office, which is struggling with the
effects of the accelerating explosion of biotech
innovations; but not for others who stayed awake at the switch, such as LabCorp, which put itself in the right place at the right
time by following and understanding trends in genetics and testing technology
and accurately predicted their accelerating progress.

If venture capital is a bellwether of trends, then faster
drug discovery, better disease therapies, and assisted self-care via
telemedicine seem about to boom. Doctors — or patients — could one
not-so-distant day perform genetic analyses using their
PC’s CD-ROM drive and an inkjet printer. (Yet, despite this and other promising approaches, skeptics still refuse to believe
that quick, cheap DNA sequencing is closer than a decade away.)

At least one drugmaker is evidently awake to RNA
interference (RNAi) — a technology barely out of theory but of such
potential it cannot be ignored. But until such time as drugs are routinely
tailored at the molecular level to the individual’s genome, anything that can speed even conventional drug discovery is a boon. A
start-up claims to have the technology to do just that, “dramatically.”

Apropos nothing except acceleration approaching warp factor eight: The sci-fi
TV series Star Trek features a doctor who appears human but is “really” a
computer-generated hologram with artificial intelligence. The United States
military is not so ambitious; they are only making a holographic patient who appears human, inside and out.

Other evidence of acceleration, with a bearing on healthcare, in recent
weeks:

• It takes Nature 15.7 million years to render one particular radioactive
  isotope half as harmful. It takes the VULCAN Petawatt
  laser about an hour to render it totally harmless. In its spare time, the
  laser can also churn out hard-to-make isotopes needed by PET scanners.
• Retail hydrogen gas stations are starting to pop up,
  to tank-up the expanding fleet of fuel-cell-powered cars, vans, and buses.
  Despite the skeptics, hydrogen power is likely to become affordable within the
  next five years for large vehicle fleets and building complexes. It is probably
  not too early to begin to factor the availability of fuel cell generators and
  vehicles into long-range strategic planning for major healthcare facilities.

Innovations can arise from actively looking for an answer to a known problem
(“need spotting”), or looking for new uses for an existing product (“solution
spotting”). They may be pure thought experiments (“mental inventions”), or the
serendipitous and sudden recognition of the significance of something (“taking
advantage of random events”). They may also arise out of “market research” and
“trend following.”

Research suggests that of these six origins, “trend following” and “mental
inventions” produce three times as many failures as successes. On the other
hand, “need spotting” produces twice as many successes as failures, “market
research” four times as many, “solution spotting” seven times as many, and
“taking advantage of random events” 13 times as many.

The researchers claim their applied taxonomy correctly predicts innovation
success or failure nine times out of ten. Given an average 20 times more
failures than successes, the Economist article suggests that it should be
possible to cut development costs substantially by predicting losers early.

Without benefit of having seen the original research, we are somewhat
skeptical of such a tool as anything more than a minor decision aid. Science and
technology in many ways depend as much on failures as successes for progress —
witness the early disappointments with monoclonal antibodies, which are now
bearing fruit.

Reference: Unknown (2003). “Expect
the unexpected.” The Economist, September 4.

Longevity

Harvard Medical School researchers have discovered that a chemical abundant
in red wine extends the lifespans of yeast, worms, and fruit flies by up to 80
percent.

The chemical, resveratrol, appears to work by forcing an enzyme that directs
other enzymes to defend or repair cells to become hyper-active, and therefore
hyper-effective. Using a “lab on a chip (perhaps like this
one) a few molecules each of thousands of different substances were
introduced into wells containing the enzyme to see if there was a reaction. The
substance that reacted best was resveratrol. When they then introduced
resveratrol into petri dishes of yeast, some of the cells were observed to
produce many more daughter cells (which is a somewhat dubious proxy for yeast
longevity) than normal. Next, they deliberately damaged human cells and treated
some with resveratrol. The treated cells recovered far better.

The researchers have also had “encouraging” early results with fruit flies
and worms. The ultimate goal is not to achieve immortality for humans, but to
extend lifespans by up to ten healthy years. The National Institute on Aging is
not recommending that people drink more red wine, but commercial spin-off
ventures are already looking to produce fountain-of-youth elixirs. If the
anti-aging effect really can be induced in humans, then Alzheimer’s patients
would be early beneficiaries.

According to one of the referenced articles, even if all diseases were
eliminated, neither life expectancy nor maximum lifespan would increase by much,
although more people would come closer to achieving the maximum (currently 122
— the age at death of the oldest person known to have lived). To live to 130 or
150 would require slowing the aging process, and while enormous strides have
been made in understanding the process at the genetic level, and in using the
knowledge to vastly extend life span in yeast, nematode worms, and fruit flies,
nothing has been proved to extend lifespan for people, and we do not know
whether humans will react as yeast does. For these reasons, no drug to slow
aging is expected to reach the market for at least ten years.

Rather than a drug to slow the rate of aging, an approach favored by some is
“regenerative medicine,” which would involved replacing old cells with
freshly-grown new ones. But that, too, is a long way from reaching the market,

References: Smith, Stephen (2003). “In
lab, seeking secret of youth: Chemical abundant in red wine appears to slow
aging in study.” Boston Globe, August 25; Weiss, Rick (2003). “Enzymes
Found to Delay Aging Process: Discovery Could Lead to Drugs to Extend Life
Span.” Washington Post, August 25, Page A02; Pollack, Andrew (2003). “Forget
Botox: Anti-Aging Pills May Be Next.” New York Times, September
21.

Faster Lithography = Faster
Computing

Photo lithography using light and chemicals to etch circuits in silicon is
the standard technique for making computer chips. Just as electron microscopes
leave optical microscopes in the dust when it comes to looking at atoms,
electron beam lithography can etch circuits at subatomic scale. The benefit is
not merely smaller conventional chips, but a quantum leap toward the circuits
and circuit components, such as quantum dots
(“Q-dots”), for quantum computing. The problem is that electron beam
lithography is painfully slow.

A new technique called erasable electrostatic lithography, using a modified
scanning tunneling microscope, cuts the time taken to etch a quantum device from
weeks to hours. Quantum wires, dots, and hills have already been demonstrated
using the new technique, which could be in practical use in five years.

Another technique, under development at Hewlett-Packard, is nano imprint
lithography, a process that uses a physical mold to create features as small as
six nanometers across on silicon wafers. One member of the HP team is taking a
different tack, making nanoscale devices that “grow” in desired structures
instead of having to be constructed as in nano imprint lithography does. He has
so far succeeded in growing 10-nanometer diameter wires.

“It might take us decades to understand [how and why things work at molecular
scale]. Or we might figure it out tomorrow,” said the HP team leader. Tomorrow
seems a safer bet.

References: Unknown (2003). “Tool Sketches
Quantum Circuits.” Technology Research News, August 27; Tristram, Claire
(2003). “Reinventing the
Transistor.” Technology Review, September.

Patent Logjam Looms

An accelerating number of increasingly complex biotechnology patent
applications is contributing to the current backlog of some 500,000 patent
applications at the U.S. Patent and Trademark Office, with the backlog projected
to double in five years. Applications take on average more than two years to
process, and complex applications can take twice that long. Genetics patent
applications are especially likely to suffer delay. Patents are necessary to
secure funding for commercial development of an innovation.

The Patent Office has a plan to speed the biotechnology patent process,
including a new fee structure to pay for more resources, and is currently
automating parts of the process. We are surprised that it has taken them so long
to begin, and predict that as the acceleration of innovations expands the
business of the Office exponentially, it will need to take advantage of
cutting-edge AI programming to do much of the work. There will not be enough
up-to-date examiners to handle the flood unaided.

Reference: Reichardt, Don (2003). “Perfecting
the pesky biotech patent process.” Atlanta Business Chronicle, September
19.

Med Tech — VCs Smell Blood

In California alone, venture capital is flowing into companies such as
Nanostream, which provides microfluidic chromatography technology enabling
pharmaceutical researchers to test 1,200 chemical samples a day, versus 50 using
traditional devices; Orqis Medical, which makes minimally invasive devices for
treating congestive heart failure; GenVault, a developer of automated DNA
storage and retrieval technology; NuVasive, a maker of spinal surgery tools; and
Supported SelfCare, which makes telemedicine technology for remote management of
chronic disease.

Reference: Friedman, Josh (2003). “Where
Tech and Medicine Meet: Venture investors see opportunities in Southland
start-ups melding health care with technology.” LA Times, August
27.

See also previous articles about microtitre
plates/drug discovery and venture
capital chasing medical technologies.

Roll Your Own Genome

University of California researchers have discovered that a conventional
computer CD-R drive and an inkjet printer can do the job of a $300,000
state-of-the-art molecular screening machine, albeit it more slowly.
Schoolchildren could soon be squelching bugs not just for the fun of it, but to
sequence its genome in their bedrooms. Doctors could sequence a patient’s genome
during an office visit.

The concept is not new, and the system appears to be still in very early
prototype form; but the point is, it has now been done.

The method is to record a digital pattern onto a blank CD, which is then fed
through an inkjet printer whose ink cartridges are filled with transparent
receptor chemicals for specific proteins. The “printed” disk is then covered
with the solution to be tested for the presence of the target molecules, and
dried. If the molecules are present, they will bind to the receptor chemicals on
the disk. The disk is then placed into the CD player, whose laser will be unable
to read the sections covered in bound molecules, and software can then map the
number and location of “errors” — target molecules — on the disc.

The inventors envision consumers buying specially prepared CDs, smearing them
with saliva, and inserting the discs into their computers to analyze, for
example, age- or exercise-induced hormonal changes. The inventors hope their
idea will seed an open-source movement in biochemistry enabling research
collaboration on a grand scale, like the open-source software movement that
turned Linux into a world-class and free computer operating system.

The prototype can only handle about 250 tests at once, compared with millions
using laboratory machines, and its accuracy and sensitivity need further
validation in a field where the slightest error could have deadly consequences,
though for consumer applications, even slightly inaccurate information may be
better than no information.

References: Austen, Ian (2003). “Now on
CD, an Inexpensive Method of Genetic Testing.” New York Times, September 25;
Asaravala, Amit (2003). “Genetic Tests in
Your Bedroom.” Wired News, August 22.

Mapping Your Genome

Several promising approaches are being actively pursued to achieve the goal
of fast and cheap sequencing of an individual’s genome.

• “Single molecule sequencing” — using a fluorescent label to mark the free
  molecules that surround DNA, then tracking which molecules are used when the DNA
  makes a copy of itself. Many sequences can be read at once.
• Bathing DNA in different frequencies of light produces a color-coded
  snapshot revealing the order of a DNA sequence.
• Shooting DNA through a nanopore and measuring the electric signals each base
  pair emits.
• Comparing one strand to the reference provided by the human genome project,
  and analyzing the differences.
• Tagging certain sequences then shooting them past a laser, which detects the
  tags as they go by.But some scientists caution that these efforts are not as well advanced
  scientifically as the press releases would have the public believe, and that the
  quick, cheap DNA sequencer is yet 10-15 years away.

  Reference: Associated Press (2003). “Tiny
  steps toward the $1,000 genome.” USA Today, September 8.

  Acceleration in Genetic Testing

  LabCorp’s Center for Molecular Biology and Pathology performs genetic tests
  for cancers, HIV, and other complex diseases, and is therefore the
  fastest-growing facility in the company’s national network, both in revenue
  growth and in the number of tests performed annually. While competitors play
  catch-up, LabCorp saw the opportunity in genetic testing early and is pushing
  forward with more new tests. By year’s end, it will introduce an ovarian cancer
  genetic test that could become as common as the Pap test. It has just begun
  offering a noninvasive genetic screening test for colorectal cancer.

  Reference: Fisher, Jean P. (2003). “Finding
  money in genes.” News & Observer, September 10.

  The Virtual Soldier

  “The Virtual Soldier Program . . . will revolutionize medical care to support
  the soldier,” says a US Defense Advanced Research Projects Agency (DARPA)
  solicitation. The program will create “a holographic medical electronic
  representation or holomer” — a virtual soldier. It will enable, among other
  things, “automatic diagnosis of battlefield injuries . . . , prediction of
  soldier performance, testing and evaluation of non-lethal weapons, and virtual
  clinical trials.”

  The holomer will incorporate “all levels of properties (genetic, molecular,
  biochemical, cellular, physiologic, organ, tissue and whole body).” Phase 1 will
  model the chest wall, heart, great vessels, lung and aorta, to create “a full
  3-D representation of the chest cavity with segmented heart, great vessels, lung
  and aorta of a generic model (visible human dataset is acceptable) which is
  fully interactive for display, query and modeling of a penetrating injury of
  each of the structures.”

  “The display of the virtual soldier must bear a high-fidelity resemblance to
  the real soldier data . . . the image of the heart must look exactly like the
  actual heart. In addition, interaction with the display must be absolutely
  intuitive — manipulating and interacting with the holomer must resemble as
  close as possible the actions that would be performed on a real person.”

  Holomers “must be storable on the U.S. Army Personnel Information Carrier
  (PIC or ??electronic dog tag??)” as well as on “the medic hand-held computer,
  standard laptop, standard desktop personal computer, DoD hospital-based medical
  record and Veterans Administration (VA) electronic medical record.”

  Reference: DARPA (2003). The Virtual Soldier.
  Undated project announcement on DARPA website.

  RNAi On the Move

  Merck has teamed up with a small biotechnology company to develop RNAi (RNA
  interference) drugs that can turn off genes involved in disease. It is “one of
  first substantial steps by a large pharmaceutical company toward making [RNAi]
  drugs,” notes the New York Times‘ Andrew Pollack. Of all the therapeutic
  technologies we have covered in HFD this year, RNAi
  (see article in the April issue) may turn out to be by far the most
  significant.

  Reference: Pollack, Andrew (2003). “Merck and
  Partner Form Alliance to Develop Drugs Based on RNA.” New York Times, p. C-16,
  September 10.

  Accelerating Drug Discovery

  Developing a new drug costs about $800 million and can take more than a
  decade. A substantial part of the cost and time is spent proving the drug is not
  toxic, and toxicity often does not show up until well into clinical trials.
  Solidus Biosciences says its planned, but as yet un-funded, machine to identify
  toxicity early in the development process would dramatically cut the time and
  the cost by rapidly testing a potential drug against a battery of enzymes
  normally found in the body, and watching for toxic effects.

  Reference: Phillips, Matthew (2003). “New
  RPI biotech hopes to speed up drug development process.” The Business
  Review, September 12.

  Radioactive No More

  Using the VULCAN Petawatt (that’s a million gigawatts) laser, scientists at
  the Rutherford Appleton Laboratory in England have turned the deadly radioactive
  iodine 129 isotope, which has a half life of 15.7 million years and must be
  encased in glass and buried deep in the earth, into the totally inert iodine 128
  isotope, safe to handle in less than an hour. But cleaning up the nuclear power
  industry will have to await development of a large-scale production version of
  the iodine 129 transmuter.

  Meantime, the technology could soon bring direct medical benefit, since the
  technique can also be used to produce the isotopes needed to operate PET
  scanners. These isotopes are currently manufactured in huge and very expensive
  cyclotrons. The lead scientist believes that this will be a practical reality
  within the next five years.

  References: Reynolds, James (2003). “Laser lights
  renders radioactive waste safe.” The Scotsman, August 6; See also article
  in The Hindu.

  Hydrogen Gas Station

  Last April, the world’s first retail hydrogen gas station opened for business
  in Iceland, where abundant geothermal and hydroelectric power is available to
  produce the hydrogen. The station’s first customers are a Mercedes concept car
  and three Daimler-Chrysler buses. Consumer vehicles will be gassing up there by
  2005.

  General Motors and Shell Hydrogen are also about to open a retail hydrogen
  pump, at a Shell station in Washington, D.C. this month. The pump will service a
  fleet of six GM HydroGen3 minivans, each powered by a 94-kilowatt fuel cell
  stack.

  Reference: Everett, Jenny (2003). “Iceland
  debuts the world’s first retail hydrogen station.” Popular Science,
  May.