WHAT the dominance of Microsoft Windows is to
personal computers, the dominance of the polymerase chain reaction
(PCR) is to biotechnology… it has transferred large numbers of dollars
from the pockets of its users to those of its patent holder, F.
Hoffmann-La Roche. But on March 28th, the gravy train began to dry up.
The original patents on the technology expired in America (they expire
in March 2006 in Europe).
"Patent ending: The polymerase chain reaction" The Economist. London: Apr 9, 2005. Vol.375, Iss. 8421; pg. 73 (subscription only)
AccessExcellence on PCR
The PCR Project at Berkeley
Videos on PCR at Roche
SCOTTISH doctors are building a unique gene database that will match
medicines to individual patients, boosting the chances of effective
treatment while reducing side-effects.
Researchers are planning to collect genetic information on 320,000 patients from blood samples taken at GPs’ surgeries.
The team at Ninewells Hospital in Dundee will use the data to
unravel the genetic mysteries behind the varied reactions different
people have to the same medicine.
By examining the DNA of patients who suffer side-effects from a
drug, or are responsive to it, they will pinpoint the genes responsible
for the variations.
This will allow doctors to give patients a course of treatment closely tailored to their genetic make-up…
[Dr Alex Doney, a consultant vascular physician at Ninewells, and leader of the project] said: "The idea is to use genetics as an extension of a
person’s medical record, in the same way as cholesterol, blood pressure
and blood sugar levels."
Doney and his team are planning to collect genetic information from
patients in Tayside by using ‘spare blood’ left over after tests on
He hopes the project will act as a pilot for similar pharmacogenetic databases in Scotland.
He said: "Normally the blood left over from blood samples would be
discarded, but we want to keep it and link it with patients’ medical
records. We estimate about 80% of the 398,000 people in Tayside will
visit their doctors over the next 10 years to have a blood test."
Richard Gray, "Coming soon: drugs to match your DNA" Scotsman. April 24, 2005.
Ninewells Hospital, Dundee
Price Waterhouse Coopers. Personalized Medicine: The Emerging Pharmacogenomics Revolution. February 2005.
Helicos Biosciences is featured in this month’s MIT Technology Review. Helicos is developing sequencing technology based on the work of Stephen Quake. The article provides a description of how their sequence-by-synthesis method works:
Helicos’s technology eliminates many of the expensive and
time-consuming steps that are central to conventional DNA sequencing.
The machine works, in essence, by photographing the process of DNA
Technicians chop up the DNA to be sequenced into
short pieces just a few hundred letters long and split each piece into
single strands, which will serve as templates for new DNA copies. They
take about 1.2 billion of those templates and chemically anchor them
side by side, like tiny bristles, on a glass slide. The Helicos machine
then washes the slide with DNA-synthesizing enzymes and fluorescently
tagged versions of the DNA bases—the molecular building blocks
represented by the familiar DNA letters. It introduces copies of just
one base at a time; wherever a template strand calls for that letter in
the next open position, the enzymes incorporate it into the growing DNA
copy. The machine then washes out the extra, unincorporated bases and
takes a picture that reveals the newly incorporated bases as dots of
lights. Once it has captured an image, the device pumps in chemicals
that stop the new bases from glowing, in preparation for another cycle
of washes and photos. The Helicos machine repeats the whole
process over and over, building up the new DNA copies one letter at a
time. A computer analyzes all the captured images to determine the
sequence of each short strand; then, using the published human genome
sequence as a guide, it pieces all the short sequences together into a
single complete one.
The Helicos sequencing machines are expected to be commercially available by late 2006 or early 2007. How will the cost of sequencing a human genome on one of these machines compare to today’s standard?
"using about 100 state-of-the-art sequencing machines to fully sequence
the 3.2 billion DNA letters that make up one person’s genome would take
six months and cost $20 million to $30 million."
"When Helicos’s commercial machine is released,
says Lapidus, it will sequence a whole genome start to finish in three
days and for a cost of $5,000."
Corie Lok. "Deciphering DNA, Top Speed" MIT Tech Review. May 2005.
Stephen Quake Lab.
Information is scant otherwise, so here is a snip from the press release:
Dr Sydney Brenner, has devised a new method for obtaining sequence information from thousands of genomes simultaneously…This method, to be developed by a new company called Population
Genetics Technologies, is expected to reduce significantly the cost of
studying large populations of genomes…The Intellectual Property and related patent applications underlying
the technology were licensed from Compass Genetics LLC, a partnership
formed several years ago by Drs Sydney Brenner, Sam Eletr and Philip
Dr Sam Eletr…“our new method, if successful…is expected to provide a significant cost advantage over other techniques which analyse one genome at a time…because our method will allow the mixing of thousands of samples in one test tube and the simultaneous interrogation of all of them in one experiment, instead of in as many experiments as there are genomes in a population. Although pooling techniques that allow simultaneous analysis of multiple genomes have been used, these only provide population-wide characteristics, such as the frequency of gene variation, and not information specific to individual genomes. We expect our technology to allow handling much larger numbers of genomes than pooling does and to have the further advantage of protecting the identities of individuals involved in any population study by allocating them a code that may be kept confidential. We expect it also be applicable to any collection of DNA molecules and genomes, whether from plants, animals, micro-organisms or humans.”
Syndey Brenner bio.
Press release. "Mass Analysis of DNA from Whole Populations." 4/20/05.
First crop of critics of the Genographic Project have emerged. Here is an overview:
- involving the public may not be useful, involving the public is expensive, the volume of respondents may be surprisingly high (Andrew Paterson, a scientist at the genetics and genomic biology group at the Sick Kids Research Institute)
- control over sample collection is weak, self-reporting is often inaccurate, look-out for contamination of samples (Steven Scherer, senior scientist at the genetics and genomic biology group at the Sick Kids Research Institute)
- should have gone the extra mile and made a biobank of the DNA samples (Kenneth K. Kidd, professor of genetics and psychiatry at Yale Med)
- should have used DNA Genotek’s Oragene kit rather than buccal swabs (company CEO Ian Curry)
Sarah Lysecki. "National Geographic’s DNA database raises doubts" itbusiness.ca, 4/18/2005.
It has been said that the four letters of DNA are not A-T-G-C, but H-Y-P-E. During a recent panel discussion sponsered by FasterCures, Venter reminded the audience that a sequence alone is not enough:
[Venter] cautioned against getting carried away with the exponential growth in
our understanding of genomics. While we may have the technology to
sequence everyone’s genome, we have no idea yet how to interpret and
use that information. Not every disease will be cured by mapping its
genome; genetic research must be integrated with the rest of the
scientific community if we’re to realize the promise of genomics. He
stressed the importance of building multi-disciplinary teams of
researchers driven to solve a specific problem.
Innovative Medical Research: New Approaches for New Outcomes. Getty Center, April 17, 2005.
Two grafs on the development of sequencing technology from a recent article in Bioscience Technology.
1) Sequencing technology is "frozen in time", still searching for a breakthrough:
Progress in gene sequencing has arisen more from improved methods than
ground-breaking instrumentation. Glenn Schulman, PharmD, marketing
manager at 454 Life Sciences (New Haven, CT) points out that gene
sequencing technology has become frozen in time circa 2000. “Things
pretty much stopped with capillary electrophoresis-based
instrumentation,” he says. “There have been incremental improvements,
but nothing truly enabling.”
454’s progress has been phenomenal since it reported its first results,
on about 25 base pairs, in late 2001. Since then scale-up has been
logarithmic: 33 kbp in 2002, 2.8 Mbp in 2003, and about 20 million bp
today (about the size of a bacterial genome) in a 4.5 hour run. Dr.
Schulman sees no end in sight to Moore’s Law-type scaling, which could
result in sequencing a whole human genome — 30 Gbp — in a matter of
days or hours.
Angelo DePalma. "Sequencing in the post-genomic age." Bioscience Technology.
My father spent several years tracing our family’s history back several hundred years. Beyond that the paper trail begins to break down. The most distant information he was able to find dates to the 15th century. Not bad. But I can beat it. For $100 National Geographic will put my family on the map of human migration patterns and tell me about my earliest human ancestors. Its called the The Genographic Project and is being supported by National Geographic, IBM, and the Waitt Family Foundation. Geneticist/Anthropologist Spencer Wells is the lead investigator of the project.
The Genographic Project Homepage
Spencer Wells, The Journey Of Man: A Genetic Odyssey. Random House, 2004.
Salvatore Salamone ‘Genographic Project’ to Track Human Migration, Bio-IT World, April 13 2005.
Carl Zimmer, Humanity’s Map, The Loom, April 13 2005.
DNA project to trace human steps, BBC April 13 2005.
Behind a privacy intrusion there is often an economic trade-off. The reduction of the cost of storing and manipulating information has led organizations to capture increasing amounts of data about individual behavior. The hunger for customization and usability has led individuals to reveal more about themselves to other parties. New trade-offs have emerged in which privacy, economics, and technology are inextricably linked: individuals want to avoid the misuse of the information they pass along to others, but they also want to share enough information to achieve satisfactory interactions; organizations want to know more about the parties with which they interact, but they do not want to alienate them with policies deemed as intrusive.
Is there a combination of economic incentives and technological solutions to privacy issues that is acceptable for the individual and beneficial to society? Is there a sweet spot that satisfies the interests of all parties?
This from a resourceful website at Carnegie Mellon that tracks info related to the economics of privacy–a thought-provoking topic for personalized medicine, which will be driven by the collection and mining of huge stores of population-wide, detailed personal health information (see LifeGene). Afford medical consumers a small number of protections and they will resist making their information available. At the same time, the more restrictions created around the free transmission of personal health information, the more difficult and costly the task of generating useful knowledge. As population studies become larger and larger, and they surely will, these issues will be of paramount importance.
Thank you to Alessandro Acquisti for maintaining this resource. I’ve added a link in the "law, policy, and ethics" section on the right, where the rest of the privacy related links reside.