Complete Genomics, a biotech start-up based in Mountain View, California, announced last week that it had produced three complete genome sequences for an average cost of $4,400 apiece. The error rate of these sequences is thought to be extraordinarily low, estimated at one in every 100,000 bases.

A number of companies, among them IBM, GE Global Research and Helicos BioSciences, have spent the last few years competing to develop low-cost sequencing technology. One of Complete Genomics's sequences used only $1,500 in materials, making it the least expensive genome to date.

The $4,400 figure doesn't tell the whole story; that's just the average value of the chemical enzymes used, and it doesn't reflect the labor or computational costs. Still, when the Human Genome Project finished the first sequence of a human genome in 2003, the cost is believed to have been at least $500 million. The latest results from Complete Genomics amount to an incredible markdown, and the company's competitors in the sequencing industry have promised even lower prices down the line.

If and when personal genome sequencing becomes something a majority of people can afford, it's likely to change almost everything about how care is administered. Whatever variations might be present in an individual's genetic code will show up in a genome sequence, including those associated with disease. Physicians would not only be able to offer preventative suggestions to their patients, but, since the genome also contains information about a person's metabolic reactions, they'd have a better chance of prescribing medicine that wouldn't cause unwanted side effects.

Earlier this year, Jay Flatley, CEO of the biotech firm Illumina, predicted that by 2019, genome sequencing will be not only affordable but routine, administered to newborns before they leave the hospital.

Of course, it might not always be a good thing to have access to the secrets of one's own genetic code. Certain genomic profiles could predict a dramatically shortened life expectancy, and it's not hard to imagine that some people wouldn't want to go about their lives with that knowledge hanging over them. The susceptibilities and predispositions revealed in a genome sequence would also be of likely (and possibly unwelcome) interest to insurers and employers.

If nothing else, the advent of routine genome sequencing is sure to complicate the vocabulary of care providers. If a baby displays a genomic marker for Niemann-Pick disease, does that count as a pre-existing condition? It's not a question we have an answer for, but we'll probably need to come up with one before long.

A detailed account of Complete Genomics's discount sequencing methods can be found at Ars Technica.

Photo by mknowles, used under Creative Commons license.

The research team at the Max Planck Institute for Evolutionary Anthology presented their findings last week at a human evolution conference. The researchers have compared the Neanderthal genome to that of modern humans of European and African descent. Because Neanderthals and modern humans coexisted in Europe, researchers have theorized that European genomes would have more similarities with the Neanderthal genome than would African genomes. However, European and African genomes have a similar number of differences from the Neanderthal genome, suggesting that modern humans in Europe outbred rather than assimilated the Neanderthals.

Earlier comparisons of mitochondrial similarly cast doubt on the Neanderthal interbreeding theory, but recent research has revealed that Neanderthals do not possess the very genes some researchers believed modern humans had received from Neanderthals. Neanderthals possess neither the microcephalin gene, linked to bulging brains in humans, nor humans’ increased fertility gene.

The team is planning to publish a rough draft of the Neanderthal nuclear genome, and hopes that a closer study of the genome will reveal more about the Neanderthal history. They believe, for example, that further analysis of the available genome will reveal whether Neanderthal practiced polygyny, with fewer males breeding with proportionally more females. But the study is hampered by the poor quality and small sample of available genetic samples, and the researchers say it will be another year or two before an adequate sequencing is complete.

[New Scientist]

The volunteers are all participating in the Personal Genome Project, a Harvard study, which as we’ve mentioned before, is attempting to create a database of 100,000 human genomes. Although other services collect genomes as well, PGP has come to public attention for taking personal information in lieu of payment:

In exchange for the decoding of their DNA, participants agree to make it available to all — along with photographs, their disease histories, allergies, medications, ethnic backgrounds and a trove of other traits, called phenotypes, from food preferences to television viewing habits.

So what has prompted these volunteers to make so much of their personal lives publically available? Each possesses, in PGP head George Church’s estimation, the equivalent of at least a master’s degree in genetics, and many have an academic and/or financial interest in furthering genetic research:

• George Church, PhD, Professor of Genetics at Harvard Medical School, Professor of Health Sciences & Technology at Harvard and MIT, and head of PGP.
• Esther Dyson, technology entrepreneur and commentator, philanthropist, and future space tourist.
• Misha Angrist, PhD, Science Editor at the Duke University Institute for Genome Sciences & Policy and author of The Genome Revolution: DNA, Health and Society.
• Keith Batchelder, MD, founder and CEO of Genomic Healthcare Strategies.
• Rosalynn Gill, PhD, founder and Chief Science Officer of Sciona.
• John Halamka, MD, MS, Chief Information Officer of the CareGroup Health System and Chief Information Officer and Dean for Technology at Harvard Medical School.
• Stanley Lapidus, Chairman and CEO of Helicos BioSciences Corp.
• Kirk Maxey, MD, manages the Donor Sibling Registry and the Cayman Biomedical Research Institute.
• James Sherley, MD, PhD, Senior Scientist at the Boston Biomedical Research Institute.
• Steven Pinker, PhD, Johnstone Family Professor of Psychology at Harvard University.

While the “PGP 10” understand the benefits and consequences of posting this sort of information online, some fear that those who follow their lead won’t be so savvy:

“I’m concerned that this could make it seem easy and cool to put your information out there when there is still a lot of stigma associated with certain genetic traits,” said Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University. “There will be new uses of this data that people can’t anticipate — and they can’t do anything to get it back.”

But some have already been lured in by PGP’s promise of a free genetic screening, which could tell them if they are predisposed toward certain diseases. In the latest issue of GQ, University of Illinois professor Richard Powers shares his own journey through PGP’s gene mapping process, including his decision to join the genetic database and what the geneticists found.

[Personal Genome Project]
Taking a Peek at the Experts’ Genetic Secrets [NY Times]
The Book of Me [GQ]

DNA sequencing is slow and takes a lot of computational power. To put it into Homer Simpson terms, the DNA is replicated, torn into little pieces, sorted out and analyzed bit by bit, then reassembled by a computer. The SMRT sequencer improves on the process because it "watches" the DNA as it is being replicated by the polymerase, reading each piece of DNA in something called the Zero-Mode Waveguide. The ZMW is a "nanophotonic visualization chamber" made by making a hole just a few tens of nanometers across in a metal film just 100 nanometers thick. Chemicals introduced into the reaction give off tiny flashes of colored light, which are detected by the highly parallel optics system (pictured). The CCD can detect the lights, and computers use that information to figure out which base pairs are in which ZMW window, decoding long strands of DNA in real-time. You could be running down to the DNA-Mart for a quick DNA scan as soon as 2013. Image by: Pacific Biosciences.

Long Reads, Short Run Time, and High Quality Data at Lower Cost. [Pacific Biosciences]

Church has good reasons for wanting piles of genomic data. As a Bloomberg article on the project says:

By matching genetic data from each person with his or her health history, Church would build a database that would link DNA variations and disease for scientists and drugmakers, the first step in deciding on treatments that can block the mutations or adjust how they work within the body.

Church also said he'll explore other human traits under genetic control. Participants will give facial and body measurements, tell researchers what time they get up in the morning, and detail other behaviors, he said.

Church has already partially sequenced genomes from 10 people, and the jump to 100,000 is under review by a Harvard ethics panel. The project ``only stops when we stop learning things,'' Church said.

We should note: there's no evidence of wrongdoing here, and Google has never explicitly said "we want to organize genetic information." True, they are major investors in the personal genomics company 23andMe, but we have every reason to believe that Big brother "don't be evil" Google will play it straight, keeping any information they have access to safe and anonymous.

But still you've got to wonder, does Google want direct access to DNA information? And if so, why?

Source: Bloomberg via SciGuy

Graphic: Personal Genome Project (Church's outfit)

According to BBC News:

They must transplant the synthetic genome into another cell so that it can use the existing machinery to "boot up" and start growing and reproducing. "It's installing the software - basically we have to boot up the genome, get it operating," said Dr [Hamilton] Smith, who won the Nobel Prize in Physiology or Medicine in 1978. "We're simply re-writing the operating software for cells - we're not designing a genome from the bottom up - you can't drop a genome into a test tube and expect it to come to life," he added.

And leave it to MIT's awesome Drew Endy to give us the big picture:

Given the work already done in Japan, building genomes almost 10 million base-pairs long - I would be surprised if by 2012 it were not technically possible to routinely design and construct the genomes of any bacteria or single celled eukaryote, which also means that it will be possible to construct some mammalian chromosomes.

The synthetic genome is based on the bacteria Mycoplasma genitalium, which sounds sort of dirty, so researchers named its synthetic counterpart Mycoplasma JCVI-1.0.

Synthetic Life Advance Reported [BBC News]