July 25, 2008
DNA Sequencing Technology Continues Rapid Advance

Technological progress in DNA sequencing continues to amaze. But political obstacles to widespread gene testing threaten to prevent full use of these advances. First off, Alexis Madrigal surveys the rapid progress in DNA sequencing technology.

A prominent genetics institute recently sequenced its trillionth base pair of DNA, highlighting just how fast genome sequencing technology has improved this century.

Every two minutes, the Wellcome Trust Sanger Institute sequences as many base pairs as all researchers worldwide did from 1982 to 1987, the first five years of international genome-sequencing efforts.

That speed is thanks to the technology underlying genomics research, which has been improving exponentially every couple of years, similar to the way computer tech improves under Moore's Law.

The DNA sequencing technologies under development promise to bring more huge strides in speed and cost reduction of DNA sequencing in the next decade.

What's clear is that the DNA sequencing technology pipeline is deep and ready to deliver innovation and reduced cost for years to come. Within the next decade, nanopores, tiny holes about 1.2 nanometers across, combined with new microscopy techniques, could even allow scientists to "read" individual DNA bases as easily as we read the letters A, C, T, G.

DNA sequencing company Pacific Biosciences just got an infusion of $100 million from Intel and other investors. Their technology might make 15 minute human DNA sequencing possible by 2013. We are that close to an enormous explosion in available DNA sequencing data.

The Menlo Park, California-based company believes SMRT will lead to a transformation in the field of DNA sequencing that will facilitate sequencing of individual genomes as part of routine medical care. Pacific Bioscience has estimated its next-generation sequencer will be available as early as 2010 and has anticipated that by 2013, its technology will be able to sequence a genome in 15 minutes.

The Pacific Biosciences technology watches individual DNA polymerase enzymes holding onto nucleotides. We are talking way small scale.

But in order to be able to detect fluorescence from just a single nucleotide without interference from others that also float around in the system, the observation volume must be made much smaller.

Enter zero-mode waveguides, or ZMWs, which are tiny wells with metal sides and a glass bottom that are made by punching holes tens of nanometers wide in a 100-nanometer aluminum film that is deposited on glass. When a laser is shone at the wells from below, it cannot penetrate them because its wavelength is bigger than the hole. The effect is similar to how microwaves cannot exit the perforated screen of a microwave oven door.

However, some attenuated light forms an evanescent field just inside the well near its bottom, creating a tiny illuminated detection volume of 20 zeptoliters, small enough to observe a single molecule of DNA polymerase holding on to a nucleotide, but no surrounding fluorescent molecules.

So you'll be able to afford to get your DNA sequenced within 5 years. Now our problem is to figure out what all the genetic differences mean. We need to collect detailed medical histories and other information about a large number of volunteers (preferably millions) so that we can compare that data along with DNA sequencing data to discover which genetic differences cause functional differences.

Update: Looking forward to getting your DNA sequenced? The states of California and New York require a doctor's permission for you to get genetic testing and sequencing done. How dare they!

You may think you own your blood and saliva and that you're free to take some of it and send it to a lab for whatever type of analysis you want.

The state of California disagrees.

If you're a California resident, the state department of health has forbidden companies that do direct-to-consumer genetic analysis from selling their services to you -- unless a doctor has given you permission to learn about your own DNA.

You aren't allowed to get information about yourself without a doctor's supervision? We are considered incapable of interpreting the results. I say that is besides the point. We aren't always capable of making other decisions that we make either. What damage is the state trying to prevent in making this rule?

The state of California is trying to get web-based gene testing services to stop serving Californians.

California becomes the second big state to crack down on companies that offer gene tests to consumers via the Web. This week, the state health department sent cease-and-desist letters to 13 such firms, ordering them to immediately stop offering genetic tests to state residents.

Could other bloggers please take up this issue and write posts complaining about this regulatory action?

Share |      Randall Parker, 2008 July 25 11:57 PM  Biotech Advance Rates

Fly said at July 26, 2008 3:27 PM:

Personal Genome Project

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