Long time readers know that I expect much more rapid advances in biotechnology because biological research is coming to resemble the computer industry with miniature lab devices designed for low cost mass manufacture and automated use. The devices operate on biological systems at the scale of individual cells and molecules. Here's another example of how much this trend cuts costs and speeds progress. Microfluidic devices will enable personal complete DNA sequencing for only $100.
It currently costs roughly $60,000 to sequence a human genome, and a handful of research groups are hoping to achieve a $1,000 genome within the next three years. But two companies, Complete Genomics and BioNanomatrix, are collaborating to create a novel approach that would sequence your genome for less than the price of a nice pair of jeans--and the technology could read the complete genome in a single workday. "It would have been absolutely impossible to think about this project 10 years ago," says Radoje Drmanac, chief scientific officer at Complete Genomics, which is based in Mountain View, CA.
Such a low cost will of course be achieved using nanofluidic devices. Basically, something like computer chips but designed to manipulate individual molecules of DNA.
Each DNA molecule will be threaded into a nanofluidics device, made by Philadelphia-based BioNanomatrix, lined with rows of tiny channels. The narrow width of the channels--about 100 nanometers--forces the normally tangled DNA to unwind, lining up like a train in a long tunnel and giving researchers a clear view of the molecule.
Cheap DNA sequencing will revolutionize the way many people mate. People will surreptitiously check the DNA sequences of prospective mating partners. "Does she have the genes I want to give to my children? If not, I'll make up some excuse about how we have different goals in life and just move on." Or "Does he have the genetic right stuff? If not, I'll tell him he's not spiritual enough for me and say I have to end it". Just how will people lie in order to avoid telling someone they are too genetically inferior for baby making?
Then there's the markets for donor sperm and eggs. With the ability to select among large numbers of egg donors and a far larger number of sperm donors the use of DNA testing will enable buyers to get much closer to their ideal genetic profile. Expect the resulting kids to be smarter, healthier, with different personalities (how exactly?) and far better looking. People who use donor sperm and egg will produce smarter and more successful kids than the average people who choose mates who will help them raise their genetically own kids.
How much and how soon will microfluidic devices speed up the development of stem cell therapies? Genetic selection of sperm, eggs, and fertilized embryos will certainly speed up human evolution. But stem cell therapies will let us rev up and rejuvenate our existing old natural design bodies.
FOSTER CITY, Calif. -- Applied Biosystems (NYSE:ABI), an Applera Corporation business, today announced a significant development in the quest to lower the cost of DNA sequencing. Scientists from the company have sequenced a human genome using its next-generation genetic analysis platform. The sequence data generated by this project reveal numerous previously unknown and potentially medically significant genetic variations. It also provides a high-resolution, whole-genome view of the structural variants in a human genome, making it one of the most in-depth analyses of any human genome sequence. Applied Biosystems is making this information available to the worldwide scientific community through a public database hosted by the National Center for Biotechnology Information (NCBI).
Does anyone reading this know (or have a way to find out) how many days or weeks this sequencing took to do?
Applied Biosystems was able to analyze the human genome sequence for a cost of less than $60,000, which is the commercial price for all required reagents needed to complete the project. This is a fraction of the cost of any previously released human genome data, including the approximately $300 million1 spent on the Human Genome Project. The cost of the Applied Biosystems sequencing project is less than the $100,000 milestone set forth by the industry for the new generation of DNA sequencing technologies, which are beginning to gain wider adoption by the scientific community.
The earliest automated DNA sequencing machine developed at CalTech (using a mass spectrometer design developed for a Mars mission) required a full time lab technician to purify the existing highest quality reagents to an even higher purity that the sequencing machine needed.
These scientists did multiple sequencings of the same genome which is needed in order to get good accuracy.
Under the direction of Kevin McKernan, Applied Biosystems' senior director of scientific operations, the scientists resequenced a human DNA sample that was included in the International HapMap Project. The team used the company's SOLiD System to generate 36 gigabases of sequence data in 7 runs of the system, achieving throughput up to 9 gigabases per run, which is the highest throughput reported by any of the providers of DNA sequencing technology.
The 36 gigabases includes DNA sequence data generated from covering the contents of the human genome more than 12 times, which helped the scientists to determine the precise order of DNA bases and to confidently identify the millions of single-base variations (SNPs) present in a human genome. The team also analyzed the areas of the human genome that contain the structural variation between individuals. These regions of structural variation were revealed by greater than 100-fold physical coverage, which shows positions of larger segments of the genome that may vary relative to the human reference genome.
"We believe this project validates the promise of next-generation sequencing technologies, which is to lower the cost and increase the speed and accuracy of analyzing human genomic information," said McKernan. "With each technological milestone, we are moving closer to realizing the promise of personalized medicine."
Before we get to personalized medicine we are going to discover what a huge number of genetic variations do to make us different in mind and body. Our perceptions of what we are as humans will be fundamentally altered. Most notably people will come out on the other side of this wave of discoveries with an altered and reduced view of the power of free will.
Remember when sequencing the DNA of just a single person was a great achievement? Now an international project will sequence 1000 times as many human genomes.
An international research consortium today announced the 1000 Genomes Project, an ambitious effort that will involve sequencing the genomes of at least a thousand people from around the world to create the most detailed and medically useful picture to date of human genetic variation. The project will receive major support from the Wellcome Trust Sanger Institute in Hinxton, England, the Beijing Genomics Institute, Shenzhen (BGI Shenzhen) in China and the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH).
Drawing on the expertise of multidisciplinary research teams, the 1000 Genomes Project will develop a new map of the human genome that will provide a view of biomedically relevant DNA variations at a resolution unmatched by current resources. As with other major human genome reference projects, data from the 1000 Genomes Project will be made swiftly available to the worldwide scientific community through freely accessible public databases.
“The 1000 Genomes Project will examine the human genome at a level of detail that no one has done before,” said Richard Durbin, Ph.D., of the Wellcome Trust Sanger Institute, who is co-chair of the consortium. “Such a project would have been unthinkable only two years ago. Today, thanks to amazing strides in sequencing technology, bioinformatics and population genomics, it is now within our grasp. So we are moving forward to build a tool that will greatly expand and further accelerate efforts to find more of the genetic factors involved in human health and disease.”
Scientists think they've found the genetic variations which are carried by at least 10% of the human population. Now they want to look for rarer variations that are carried by as few as 1% of the population.
The scientific goals of the 1000 Genomes Project are to produce a catalog of variants that are present at 1 percent or greater frequency in the human population across most of the genome, and down to 0.5 percent or lower within genes. This will likely entail sequencing the genomes of at least 1,000 people. These people will be anonymous and will not have any medical information collected on them, because the project is developing a basic resource to provide information on genetic variation. The catalog that is developed will be used by researchers in many future studies of people with particular diseases.
“This new project will increase the sensitivity of disease discovery efforts across the genome five-fold and within gene regions at least 10-fold,” said NHGRI Director Francis S. Collins, M.D., Ph.D. “Our existing databases do a reasonably good job of cataloging variations found in at least 10 percent of a population. By harnessing the power of new sequencing technologies and novel computational methods, we hope to give biomedical researchers a genome-wide map of variation down to the 1 percent level. This will change the way we carry out studies of genetic disease.”
Within a few years this project will be collecting more sequence information in 2 days than was collected in all of last year.
“This project will examine the human genome in a detail that has never been attempted – the scale is immense. At 6 trillion DNA bases, the 1000 Genomes Project will generate 60-fold more sequence data over its three-year course than have been deposited into public DNA databases over the past 25 years,” said Gil McVean, Ph.D., of the University of Oxford in England, one of the co-chairs of the consortium’s analysis group. “In fact, when up and running at full speed, this project will generate more sequence in two days than was added to public databases for all of the past year.”
The acceleration of DNA sequencing technologies is going forward much faster than the Moore's Law rate of advance of computer power which takes a couple of years to achieve a single doubling of power. DNA sequencing technologies are speeding up by orders of magnitude in a few years.
The 1000 Genomes Project will probably be followed by the Million Genomes Project to find very rare genetic variations. Plus, at the same time we are witnessing a flood of discoveries about what each of the genetic variations mean in terms of disease risk and about which genetic variations cause which differences between people. We are getting very close to the discovery of large numbers of genetic variations that determine cognitive abilities and behavioral tendencies. Within 10 years embryo selection guided by genetic testing will become the rage among those who want to have the highest performing offspring.
Venture capitalists see biotechnology as about to take off.
Venture capitalists pumped a record $9.1 billion into privately held U.S. biotechnology and medical device companies last year, in hopes of making discoveries they can sell to larger drugmakers.
Biotechnology and medical device companies raised 20 percent more cash in the U.S. last year than in 2006, according to a report by accounting firm PricewaterhouseCoopers and the National Venture Capital Association.
This bodes well for the development of rejuvenation therapies. Biotechnology is going to advance much more rapidly with lots of venture capital investments flowing into start-ups. The amounts of money getting invested suggests the venture capitalists think biotechnology has finally advanced far enough that it can really start delivering large returns on investment.
If you look at the chart on page 3 of the full report (PDF) you will see that the second quarter of 2007 (2Q 07) was a stronger quarter than 3Q 07 for venture capital investment overall and for biotechnology and for medical devices and equipment.
But you will also notice one category is leaping upward very rapidly: Industrial/Energy. It nearly doubled from $543 million in 2Q 07 to $921 million in 3Q 07. That puts it close to the $1,091 million for biotech in Q3 07. High oil prices are probably causing a shift of investment from biotech and other areas to energy. As we move past the peak of oil production and the world decline of available oil starts to take hold that shift could intensify. So Peak Oil is an obstacle to the development of rejuvenation therapies.
The trend of using computer semiconductor technologies to manipulate biological material promises to revolutionize biological science and biotechnology. Orders of magnitude cost reductions become possible when very small devices are fabricated to manipulate cells and components of cells. Researchers at University of Illinois have created a simulated design for a nanopore-based DNA sequencer that could drastically cut DNA sequencing costs.
CHAMPAIGN, Ill. — Using computer simulations, researchers at the University of Illinois have demonstrated a strategy for sequencing DNA by driving the molecule back and forth through a nanopore capacitor in a semiconductor chip. The technique could lead to a device that would read human genomes quickly and affordably.
Being able to sequence a human genome for $1,000 or less (which is the price most insurance companies are willing to pay) could open a new era in personal medicine, making it possible to precisely diagnose the cause of many diseases and tailor drugs and treatment procedures to the genetic make-up of an individual.
“Despite the tremendous interest in using nanopores for sequencing DNA, it was unclear how, exactly, nanopores could be used to read the DNA sequence,” said U. of I. physics professor Aleksei Aksimentiev. “We now describe one such method.”
Cheap DNA sequencing is going to most dramatically change reproductive practices. Once embryos can be fully DNA tested and the meaning of all genetic variations become known then a substantial fraction of the population wil use in vitro fertilization and pre-implantation genetic diagnosis (PIGD or PGD) to select embryos to start pregnancies with. That act of selection will speed up human evolution by orders of magnitude even before we start introducing genetic variations with genetic engineering.
An article in The Scientist provides a sense of how much DNA sequencing costs have fallen. At the bottom of that page they show 3 costs from 3 different sequencing instruments for doing a sequencing of the Drosophila fly genome. The established ABI 3730 has a sequencing cost for this job of $650,000. The 454 Life Sciences instrument costs $132,000 for the same job. Big cut in cost, right? But if you paid $132,000 you paid too much. Using the Solexa instrument costs $12,500 for the same job. Wow.
The article states that each of these instruments are more appropriate for different classes of problems. For example, RNA sequencing is one kind of problem and the article reports on a huge advance in how much RNA sequencing one MIT lab can now do with newer machines:
David Bartel at MIT's Whitehead Institute for Biomedical Research and colleagues have been using new sequencing technologies to investigate new classes of small RNAs. With standard sequencing in 2003, Bartel says he was happy to get 4,000 RNAs sequenced. In 2006, using 454 sequencing he could get 400,000, and this year, using the Solexa instrument, he'll get 50 million.
So Bartel is getting 4 orders of magnitude more data per year over just 4 years time. He can ask questions and look for answers in areas that were totally beyond his reach just 4 years ago. Of course 4 years from now he'll be able to ask still more questions he can't ask now and get answers at an even faster rate. This pattern of advance makes me very optimistic about how much scientists and bioengineers will be able to accomplish in 10 and 20 years time. These tools have become so powerful because they've become smaller. The pattern is very similar to the pattern we see in the computer industry. Successive waves of technology become smaller, faster, cheaper, more powerful.
When do these advances reach a point where, say, stem cell manipulation to produce useful therapies becomes really easy? There's a point on the road ahead where therapies we can only dream about today become easy to create. Once we can produce replacement parts using cell therapies and organs grown in vats full body rejuvenation (with the unfortunate exception of the brain) will be within reach. We'll also need really excellent gene therapies to take on the more difficult task of brain rejuvenation. Though cell therapies will still deliver benefits to the brain, for example in the form of rejuvenated blood vessels.
Silicon technology applied to microfluidics is going to revolutionize biological science.
Integrating silicon microchip technology with a network of tiny fluid channels, some thinner than a human hair, researchers at The Johns Hopkins University have developed a thumb-size micro-incubator to culture living cells for lab tests.
In a recent edition of the journal IEEE Transactions on Biomedical Circuits and Systems, the Johns Hopkins researchers reported that they had successfully used the micro-incubator to culture baby hamster kidney cells over a three-day period. They said their system represents a significant advance over traditional incubation equipment that has been used in biology labs for the past 100 years.
"We don't believe anyone has made a system like this that can culture cells over a period of days autonomously," said Jennifer Blain Christen, lead author of the journal article. "Once it's set up, you can just walk away."
Note the lack of need for daily labor-intensive care. The system is automated. Automation speeds progress, cuts costs, increases consistency and quality.
I expect that the rate of advance in biological sciences and biotechnology is going to greatly accelerate in the next few decades because of microfluidics and computer simulations. Experiments will get done more rapidly and with larger numbers of experiments done in parallel as cheap devices lower the material and labor costs of each experiment.
This ability to accelerate advances makes me very optimistic about the prospects for the development of rejuvenation therapies. Automation will enable the development of much more powerful manipulations of cells and tissues. The automation and miniaturization will enable cheap ways to introduce experimental conditions and measure the results automatically.
While the days of high market growth, driven by the human genome project, are behind us, the era of personal genomics is yet to begin. Next generation genomics technologies are breathing new life into the market, and are expected to contribute to the robust growth of the U.S. genomics market between 2005 and 2012. Top industry participants are successfully developing specific applications for each evolutionary stage of the genomics research process, and are likely to maintain revenue streams, while strategically positioning themselves to penetrate the future markets for clinical applications of genomic technologies.
New analysis from Frost & Sullivan (drugdiscovery.frost.com), Strategic Analysis of U.S. Genomics Markets, reveals that revenues in this market totaled $1.85 billion in 2006, and is likely to reach $3.69 billion in 2012.
That doubling in revenue will occur along with a huge increase in the amount of DNA sequence produced per dollar spent. Leading industry figures expect a 3 order of magnitude drop in sequencing costs perhaps as soon as 5 years from now.
Scientists are doing most of the DNA sequencing for their own research purposes today. But at some point in the next 5 to 10 years the desire to learn one's own personal genome sequences will become the biggest source of demand for DNA sequencing services. Also demand will grow for surreptitious DNA sequencing services so that people can learn the DNA sequences of love interests, prospective employees, celebrities, and business competitors. Science will turn up all sorts of practical uses of DNA sequence information and your genetic privacy will become very hard to protect.
Microfluidic chips are going to speed up the rate of biological experimentation by orders of magnitude. Here is another example of the power of microfluidics for studying biological systems.
CHAMPAIGN, Ill. — Researchers at the University of Illinois have developed a method for culturing mammalian neurons in chambers not much larger than the neurons themselves. The new approach extends the lifespan of the neurons at very low densities, an essential step toward developing a method for studying the growth and behavior of individual brain cells.
The technique is described this month in the journal of the Royal Society of Chemistry – Lab on a Chip.
“This finding will be very positively greeted by the neuroscience community,” said Martha Gillette, who is an author on the study and the head of the cell and developmental biology department at Illinois. “This is pushing the limits of what you can do with neurons in culture.”
The small scale allows much greater sensitivity of measurement.
First, the researchers scaled down the size of the fluid-filled chambers used to hold the cells. Chemistry graduate student Matthew Stewart made the small chambers out of a molded gel of polydimethylsiloxane (PDMS). The reduced chamber size also reduced – by several orders of magnitude – the amount of fluid around the cells, said Biotechnology Center director Jonathan Sweedler, an author on the study. This “miniaturization of experimental architectures” will make it easier to identify and measure the substances released by the cells, because these “releasates” are less dilute.
“If you bring the walls in and you make an environment that’s cell-sized, the channels now are such that you’re constraining the releasates to physiological concentrations, even at the level of a single cell,” Sweedler said.
The method used to create the microfluidic chambers
Second, the researchers increased the purity of the material used to form the chambers. Cell and developmental biology graduate student Larry Millet exposed the PDMS to a series of chemical baths to extract impurities that were killing the cells.
This technique allows measurement of cellular secretions.
Millet also developed a method for gradually perfusing the neurons with serum-free media, a technique that resupplies depleted nutrients and removes cellular waste products. The perfusion technique also allows the researchers to collect and analyze other cellular secretions – a key to identifying the biochemical contributions of individual cells.
This technique allows neurons to live longer in culture. Hence more experimental data can be collected and more kinds of processes studied.
This combination of techniques enabled the research team to grow postnatal primary hippocampal neurons from rats for up to 11 days at extremely low densities. Prior to this work, cultured neurons in closed-channel devices made of untreated, native PDMS remained viable for two days at best.
The development of microfluidic devices will bring changes in biotechnology as revolutionary as the changes which miniaturization have caused in the electronics industry. Microfluidics will enable massive parallelism and automation of experiments at very low cost.
MIT researchers have developed a microfluidic chip that automates research on the worm Caenorhabditis elegans (C. elegans).
Genetic studies on whole animals can now be done dramatically faster using a new microchip developed by engineers at MIT.
The new "lab on a chip" can automatically treat, sort and image small animals like the 1-millimeter C. elegans worm, accelerating research and eliminating human error, said Mehmet Yanik, MIT assistant professor of electrical engineering and computer science.
The advance rate in biotechnology is going to accelerate because the technologies developed by the computer industry to work at increasingly smaller scales are getting reused to develop chips that can do biological research. The "lab on a chip" approach is going to allow an automation and acceleration of biological experiments that will speed up research by orders of magnitude.
Each worm can get routed through the chip and manipulated in different ways to do a very large variety of experiemnts in an automated fashion..
"Normally you would treat the animals with the chemicals, look at them under the microscope, one at a time, and then transfer them," Yanik said. "With this chip, we can completely automate that process."
The tiny worms are flowed inside the chip, immobilized by suction and imaged with a high resolution microscope. Once the phenotype is identified, the animals are routed to the appropriate section of the chip for further screening.
The worms can be treated with mutagen, RNAi or drugs before they enter the chip, or they can be treated directly on the chip, using a new, efficient delivery system that loads chemicals from the wells of a microplate into the chip.
"Our technique allows you to transfer the animals into the chip and treat each one with a different gene silencer or a different drug," Yanik said.
Chips can be mass produced at low cost. Chips that can manipulate whole worms can probably manipulate cells or small groups of cells. So this chip has application beyond C. elegans.
Natural selection can only select between mutations that occur naturally. The number of mutations that might occur naturally in humans is limited by the number of humans and by which mutations occur in each human. In theory if one could search through a much larger set of mutations one should be able to find genes which code for better enzymes and better versions of other components of our body. Some scientists have shown that they can generate and test a large number of potential enzymes to find new designs.
Living cells are not the only place where enzymes can help speed along chemical reactions. Industrial applications also employ enzymes to accelerate reactions of many kinds, from making antibiotics to removing grease from clothing. For the first time, scientists have created a completely new enzyme entirely in vitro, suggesting that industrial applications may one day no longer be limited to enzymes that can be derived from natural biological sources.
HHMI investigator Jack W. Szostak and Burckhard Seelig, a postdoctoral associate in his Massachusetts General Hospital and Harvard Medical School laboratory, show in a paper published in the August 16, 2007, issue of the journal Nature the steps they took to create the artificial enzyme, an RNA ligase that catalyzes a reaction joining two types of RNA chains.
This group at Harvard thinks they can develop better tools to select for enzymes that rise to a higher level of performance.
Szostak's approach relies instead on evolution. The technique enabled the researchers to generate a new RNA ligase without any pre-existing model of how it would work. According to Szostak, “There is no known biological enzyme that carries out this reaction.”
To create one, the researchers assembled a library of 4 trillion small protein molecules - each with slight variations on an initial protein sequence — then subjected those molecules to evolutionary selection in the laboratory. “Here,” Szostak says, “the hard work is in designing a good starting library, and an effective selection process. Since we do not impose a bias on how the enzyme does its job, whatever mechanism is easiest to evolve is what will emerge.”
The enzyme that emerged from the group's experiments is what Szostak characterizes as “small and not very stable, and not very active compared to most biological enzymes.” Nevertheless, Szostak's group is optimistic about their ability to select for versions of the enzyme that are more stable and more active.
Evolution by selection between whole organisms is too slow a way to turn up better designs. Computer simulations and automated lab equipment that generates more real life variations of proteins will some day allow us to search much more deeply through the space of all possible protein shapes to turn up much better genes. In order to give ourselves higher performing bodies we will some day replace some human genes with variants found in labs.
A new report on a set of genes discovered which contribute to a form of heart disease is less interesting for the discovery than for the tools developed which made the discovery possible. Development of a much cheaper and very sensitive technique for measuring message RNA expression levels enabled the discovery.
The one-gene, one-disease concept is elegant, but incomplete. A single gene mutation can cause many other genes to start—or stop—working, and it may be these changes that ultimately cause clinical symptoms. Identifying the complete set of affected genes used to appear impossible. Not anymore.
Studying genetically modified mice, researchers led by Christine E. Seidman, a Howard Hughes Medical Institute investigator at Brigham and Women's Hospital, and her husband Jonathan G. Seidman, who is at Harvard Medical School, have identified hundreds of genes with altered expression in preclinical hypertrophic cardiomyopathy. The study, which is coauthored by colleagues at Harvard Medical School, is published in the June 9, 2007, issue of the journal Science. The discovery could help scientists define the pathways that lead to the disease and lead to the discovery of targets for early detection, prevention, and treatment.
A new technique provides a highly sensitive way of measuring gene expression levels.
To obtain a complete picture of the genetic changes associated with the disease, the researchers developed a new gene sequencing technique called polony multiplex analysis of gene expression, or PMAGE. The technique can find messenger RNA transcripts—the directions for making a protein, spun out from the DNA of an active gene—that occur as rarely as one copy for every three cells.
PMAGE drops costs by an order of magnitude.
The industry standard for gene sequencing is serial active gene expression, or SAGE. "There are a couple of labs that have been dedicated to developing this technology," Seidman said, including HHMI investigator Bert Vogelstein at Johns Hopkins and George Church at Harvard. But PMAGE analysis costs between 1/20 and 1/9 of a comparable SAGE analysis, making it more appropriate for the kind of large-scale expression profiling undertaken in this study, she explained. "With SAGE, you can't afford to sequence 4 million transcripts."
These order of magnitude cost drops in assorted techniques for measuring genetic sequences and gene expression levels just keep coming. As the costs of measurement and data collection keep falling the rate at which scientists figure out what genes do keeps accelerating.
Many more order of magnitude cost drops for genetics and molecular biology lay in store in the future. A coming enormous flood of discoveries enabled by biotechnological advances will sweep through and revolutionize medicine.
DNA double helix co-discoverer James D. Watson has had his DNA sequenced at a much lower cost than previous genome sequencing attempts.
On Thursday, James Watson was handed a DVD containing his entire genome, sequenced in the past few months by 454, a company based in Branford, CT, that's developing next-generation technologies for efficiently reading the genome. At a cost of $2 million, 454 sequenced Watson's genome for roughly an order of magnitude less than it would have cost using traditional machines.
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The $2 million and two months that it took to sequence Watson's genome is a far cry from the more than ten years and $3 billion required for the Human Genome Project's reference genome, released in 2003.
454 Life Sciences claims their DNA sequencing cost for Watson's genome was only $1 million.
454 Life Sciences Corporation, in collaboration with scientists at the Human Genome Sequencing Center, Baylor College of Medicine, announced today in Houston, Texas, the completion of a project to sequence the genome of James D. Watson, Ph.D., co-discoverer of the double-helix structure of DNA. The mapping of Dr. Watson's genome was completed using the Genome Sequencer FLX(TM) system and marks the first individual genome to be sequenced for less than $1 million.
And technology companies like Illumina, Applied Biosystems and 454 Life Sciences, which solicited Dr. Watson’s DNA to prove its abilities, say the price of a complete human genome has already dropped to $100,000. They are competing for a $10 million “X prize” to sequence 100 human genomes within 10 days. (Dr. Watson’s took about two months.)
The rapid advance of DNA testing technologies is possible because DNA is small and DNA testing relies on computer chip technologies. While I've made this claim for years this latest news provides a much dramatic demonstration that this trend is really happening. This rate of advance that bodes well for future advances across a wide range of biotechnologies.
What will come from very cheap DNA sequencing? Lots of things:
Most of us will live to see full genome testing become commonplace.
Single DNA letter differences have garnered most of the popular and scientific attention for the study of human genetic differences. But larger genetic differences such as large copy variations (where people differ in how many copies they have of genes and sections of genes) have come under greater scrutiny as researchers have developed techniques to measure these differences. Studies of large DNA structural variations have begun to bear fruit.
A major new effort to uncover the medium- and large-scale genetic differences between humans may soon reveal DNA sequences that contribute to a wide range of diseases, according to a paper by Howard Hughes Medical Institute investigator Evan Eichler and 17 colleagues published in the May 10, 2007, Nature. The undertaking will help researchers identify structural variations in DNA sequences, which Eichler says amount to as much as five to ten percent of the human genome.
Past studies of human genetic differences usually have focused on the individual “letters” or bases of a DNA sequence. But the genetic differences between humans amount to more than simple spelling errors. “Structural changes — insertions, duplications, deletions, and inversions of DNA — are extremely common in the human population,” says Eichler. “In fact, more bases are involved in structural changes in the genome than are involved in single-base-pair changes.”
Efforts to estimate the amount of genetic difference between people and groups have produced underestimates of the real differences. The newer studies of genetic differences which measure large copy variations (e.g. differences in the number of copies of genes or sections of genes) are finding much larger differences between humans. I suspect these differences show how much local selective pressure humans experiences in each local environmental niche they moved into. We are not as alike as the politically correct would have us believe.
Eichler and colleagues are searching for large copy variations in DNA taken from 62 people.
Using DNA from 62 people who were studied as part of the International HapMap Project, they are creating bacterial “libraries” of DNA segments for each person. The ends of the segments are then sequenced to uncover evidence of structural variation. Whenever such evidence is found, the entire DNA segment is sequenced to catalog all of the genetic differences between the segment and the reference sequence.
The result, says Eichler, will be a tool that geneticists can use to associate structural variation with particular diseases. “It might be that if I have an extra copy of gene A, my threshold for disease X may be higher or lower.” Geneticists will then be able to test, or genotype, large numbers of individuals who have a particular disease to look for structural variants that they have in common. If a given variant is contributing to a disease, it will occur at a higher frequency in people with the disease.
Their use of DNA from people studied in the International HapMap Project creates synergies between the databases generatd by each effort. The International HapMap Project involves measuring single letter differences. Some of the single letter differences correlated with variations in structures such as deletion mutations and in number of copies of each gene.
We live in the twilight of the era of when little has been known about how genetic variations create human variations in health, appearances, intelligence, personality and other human qualities. 20 years from now we are going to know in enormous detail which genetic variations matter and how they matter. Continued declines in the cost of DNA testing will provide scientists with orders of magnitude more genetic data than they have now.
Once we know what most of the genetic variations mean I expect many changes in how we live our lives. For example, I expect those involved in romantic courtships to either surreptitiously get DNA samples from potential mates or demand DNA testing info as a prelude to serious courting.
Here's another example of the trend toward massive parallelism and micro-miniature devices for manipulating biological systems. A chip can monitor the binding affinity of 12,000 molecules at a time.
May 1, 2007 -- A chemist at Washington University in St. Louis is making molecules the new-fashioned way — selectively harnessing thousands of minuscule electrodes on a tiny computer chip that do chemical reactions and yield molecules that bind to receptor sites. Kevin Moeller, Ph.D., Washington University professor of chemistry in Arts & Sciences, is doing this so that the electrodes on the chip can be used to monitor the biological behavior of up to 12,000 molecules at the same time.
Moeller thinks he can automate the production of a variety of molecules and the testing of their affinity to receptors.
But, with an electrochemically addressable computer chip, provided in great abundance by one of his sponsor's, CombiMatrix in Seattle, Moeller saw a way of probing the binding of a library with a receptor without the need for washing by putting each member of the molecular library by an electrode that can then be used to monitor its behavior.
The electrochemically addressable chips being used represent a new environment for synthetic organic chemistry, changing the way chemists and biomedical researchers make molecules, build molecular libraries and understand the mechanisms by which molecules bind to receptor sites.
"We believe we can move most of modern synthetic organic chemistry to this electrochemically addressable chip. In this way, a wide variety of molecules can be generated and then probed for their biological behavior in real-time," said Moeller. "It's a tool, still being developed, to map receptors. We're right at the cusp of things."
Cells are covered with and contain a large variety of receptors. The ability to automate the production and screening of compounds that might bind at each kind of receptor can accelerate the search for new drugs and other biomedically useful compounds.
Biochips controllable by computers open up the prospect of highly automated science. Rather than mess around with test tubes, beakers, and the like scientists will run software that'll create and automatically test millions of chemicals looking for desired interactions.
Polymerase chain reactions (PCRs) are widely used to synthesize DNA as part of DNA sequencing work. Dr. Victor Ugaz at Texas A&M University has found a way to speed up the PCR DNA copying process at very low cost.
A pocket-sized device that runs on two AA batteries and copies DNA as accurately as expensive lab equipment has been developed by researchers in the US.
The device has no moving parts and costs just $10 to make. It runs polymerase chain reactions (PCRs), to generate billions of identical copies of a DNA strand, in as little as 20 minutes. This is much faster than the machines currently in use, which take several hours.
The development of cheap miniature devices is the future of biotechnology and is going to do to biotechnology what miniaturization has done to computer technology. Therefore we should expect a huge acceleration of the rate at which biological science advances and the development of very cheap methods of repair of aged bodies.
Dr. Ugaz uses convection to move the PCR process through a series of steps.
Currently, PCR faces a time issue, as it is typically ran in a thermocycler, averaging between one and three hours. Using a convective flow system, the process runs faster and more efficient, using natural convection and buoyancy forces to create the required temperature cycles.
By eliminating the need for dynamic external temperature control, a convective flow-based system is capable of achieving performance equal to or exceeding that of conventional thermocyclers in a greatly simplified format, This level of simplicity is a significant departure from previous attempts to construct novel thermocycling equipment, where added complexities often far outweigh any potential performance gains, We propose a research effort targeted at developing a new generation of thermocycling equipment offering improved performance at a significantly lower cost, thereby making PCR practical for use in a wider array of settings.
Researchers like Dr. Ugaz who work on methods to speed up and miniaturize technology used to manipulate biological materials are going catalyze a revolution in biomedical science and biotechnology.
Thanks to Brock McCusick for the tip.
Some Purdue University researchers have developed a silicon-based device that can anchor strands of DNA in nanopores for use in DNA testing.
WEST LAFAYETTE, Ind. - Researchers at Purdue's Birck Nanotechnology Center have shown how "nanopore channels" can be used to rapidly and precisely detect specific sequences of DNA as a potential tool for genomic applications in medicine, environmental monitoring and homeland security.
The tiny channels, which are 10 to 20 nanometers in diameter and a few hundred nanometers long, were created in silicon and then a single strand of DNA was attached inside each channel.
Other researchers have created such channels in the past, but the Purdue group is the first to attach specific strands of DNA inside these silicon-based channels and then use the channels to detect specific DNA molecules contained in a liquid bath, said Rashid Bashir, a professor in the School of Electrical and Computer Engineering and the Weldon School of Biomedical Engineering.
The reuse of computer industry technologies to manipulate and measure biological materials at very small scales promises to accelerate the rate of advance of biotechnology and biological science.
The method makes use of known sequences to detect affinities between anchored and floating strands of DNA.
"When the DNA molecules in the bath are perfectly complementary to those in the channels, then this current pulse is shorter compared to when there is even a single base mismatch," Iqbal said. Being able to detect specific DNA molecules quickly and from small numbers of starting molecules without the need to attach "labels" represents a potential mechanism for a wide variety of DNA detection applications.
Note that this isn't really sequencing where any order of DNA letters can be detected. This approach requires use of strands of DNA that have known sequences. So it won't work well for detecting relatively rare genetic variations (and we each have some rare genetic variations). But nanopore-based DNA sequencers might eventually perform full sequencing of genomes so that all genetic variations existing in one organism can be detected.
Sometimes it helps to have a “cheat sheet” when you are working on a problem as difficult as deciphering the relationships among hundreds of thousands of genes. At least that's the idea behind a powerful new technique developed by Howard Hughes Medical Institute (HHMI) researchers to analyze how genes function together inside cells.
The new approach is called epistatic miniarray profiles (E-MAP). The scientists who developed it — HHMI investigator Jonathan S. Weissman, HHMI postdoctoral fellow Sean Collins, and colleague Nevan Krogan, who are all at the University of California, San Francisco — have used E-MAP to unravel a key process that prevents DNA damage during cellular replication.
In the first use of this technique researchers tested for 200,000 different gene interactions.
Using the new technique, which enabled them to rapidly analyze more than 200,000 gene interactions, the researchers have made a discovery that helps explain how cells mark which sections of DNA have been replicated during cell division. If the marking process goes awry, DNA becomes damaged as it is copied.
Hundreds of yeast colonies can be grown in the same agar plate and their speed of growth can be measured and analyzed automatically with software. Since yeast share many genes with humans these studies will turn up interactions that provide insight into human biology as well.
The key to E-MAPs is the ability to eliminate single genes or gene pairs and then analyze how each change impacts the growth of yeast colonies. Each yeast colony grows in a tiny spot on an agar plate, and each plate holds around 750 colonies. Software makes it possible to determine the growth rate of each colony and then compare the effect on growth of eliminating one gene at a time with the effect when two genes are simultaneously disabled.
The scientists looked only at the genes involved in maintaining and replicating chromosomes.
The end result is a database that details the functional relationship of each gene to every other gene studied, revealing cases where the product of one gene depends on a second gene in order to carry out its cellular functions. In this experiment, Weissman's team looked at 743 yeast genes involved in basic chromosome biology. “We wanted to look at everything that had to do with chromosome biology, including DNA replication, DNA repair, transcription to RNA, and so on,” said Weissman. “These are very basic cellular processes that are conserved from yeast to man.”
But this same technique could be applied to other subsets of genes to study other aspects of cellular metabolism. This is the way biology is going: Rather than studying one or two things at once thousands of genes or interactions get measured at a time. Automated equipment and methods for working with large numbers of very small samples allows massive parallelism and orders of magnitude more data collected per experiment.
A slice of semiconductor silicon turns out to make a useful filter for small biological molecules.
A newly designed porous membrane, so thin it's invisible edge-on, may revolutionize the way doctors and scientists manipulate objects as small as a molecule.
The 50-atom thick filter can withstand surprisingly high pressures and may be a key to better separation of blood proteins for dialysis patients, speeding ion exchange in fuel cells, creating a new environment for growing neurological stem cells, and purifying air and water in hospitals and clean-rooms at the nanoscopic level.
At more than 4,000 times thinner than a human hair, the new barely-there membrane is thousands of times thinner than similar filters in use today.
This silicon is from the crystals routinely grown for computer semiconductor chip manufacturing. So here's yet another example of how the computer semiconductor industry is producing materials moldable into biologically useful devices.
The membrane is a 15-nanometer-thick slice of the same silicon that's used every day in computer-chip manufacturing. In the lab of Philippe Fauchet, professor of electrical and computer engineering at the University, Striemer discovered the membrane as he was looking for a way to better understand how silicon crystallizes when heated.
He used such a thin piece of silicon—only about 50 atoms thick—because it would allow him to use an electron microscope to see the crystal structure in his samples, formed with different heat treatments.
Back in the 1950s, 1960s, and well into the 1970s all computers were seen as large devices that filled up large rooms. But beneath the surface a technological revolution of doublings in power and halvings in costs kept repeating again and again. Suddenly the computer chips became cheap enough to put into desktop personal computers and computing became useful for the masses. Well, the same is going to happen with microfluidic devices and DNA gate arrays.
After years of technological changes only visible inside of research labs the technological advances for making miniature biochips will reach a critical mass where suddenly they will spread out into the mass market. Personal DNA testing in the private of your own home will give you your DNA sequence uploaded into your home computer. Also, implantable biochips will let you watch your blood chemistry in real time and microfluidic devices will make it possible for you to synthesize your own drugs and other treatments.
What I see coming: downloadable free software that'll program your home microfluidic biochips to make unapproved and restricted drugs and biochemical components. Just as we can download software that'll enhance what our computers can do we will be able to download an ever growing set of programs with instructions for orchestrating microfluidic biochips to more and more kinds of biochemical products.
As regular readers know, I keep arguing that the biological sciences and biotechnology are going to advance at a rate similar to the rate of advance in the computer industry. Why? Computer technologies adapted to labs such as microfluidic devices and DNA gate arrays will displace old style flasks, beakers, human-viewed microscopes, and the like. Here's another example of this trend. Some scientists at U Wisc-Madison have used computer chip fabrication technologies to produce a nanoscale device that can separate out individual strands of DNA in preparation for sequencing them.
Now, however, scientists have developed a quick, inexpensive and efficient method to extract single DNA molecules and position them in nanoscale troughs or "slits," where they can be easily analyzed and sequenced.
The positioning in troughs is a needed precursor step before reading the DNA letters in each strand. So these scientists have moved a big (or incredibly small) step closer toward very small and therefore very cheap DNA sequencing devices.
The technique, which according to its developers is simple and scalable, could lead to faster and vastly more efficient sequencing technology in the lab, and may one day help underpin the ability of clinicians to obtain customized DNA profiles of patients.
The new work is reported this week (Feb. 8, 2007) in the Proceedings of the National Academies of Science (PNAS) by a team of scientists and engineers from the University of Wisconsin-Madison.
"DNA is messy," says David C. Schwartz, a UW-Madison genomics researcher and chemist and the senior author of the PNAS paper. "And in order to read the molecule, you have to present the molecule."
Since computer technology will drive biological technology forward at a rate similar to what we see in the computer industry the future rate of development of new knowledge and eventually new treatments will far exceed what we've seen in the past.
The computer industry is providing the technologies that are accelerating the rate of biotechnological advancement. Semiconductor fabrication technology provided these researchers the tools they needed to fabricate a device that can separate out single strands of DNA.
To attack the problem, Schwartz and his colleagues turned to nanotechnology, the branch of engineering that deals with the design and manufacture of electrical and mechanical devices at the scale of atoms and molecules. Using techniques typically reserved for the manufacture of computer chips, the Wisconsin team fabricated a mold for making a rubber template with slits narrow enough to confine single strands of elongated DNA.
The ability to sequence individual DNA strands will cost less than sequencing of larger amounts of material. Mass production of chips that can sequence DNA from a single cell will make personal DNA profiles commonplace. Also, the ability to sequence a single cell's DNA will find use in criminology, cancer research, and in choice of custom cancer treatments.
Some bioengineers at UCSD are building a model to simulate parts of human metabolism.
Bioengineering researchers at UC San Diego have painstakingly assembled a virtual human metabolic network that will give researchers a new way to hunt for better treatments for hundreds of human metabolic disorders, from diabetes to high levels of cholesterol in the blood. This first-of-its-kind metabolic network builds on the sequencing of the human genome and contains more than 3,300 known human biochemical transformations that have been documented during 50 years of research worldwide.
Note that these people are engineers, not scientists. They are treating the human body as just another complex system to engineer. They are using simulation just as engineers simulate airplanes, cars, and other systems designed by humans. Their simulations are a prelude to efforts to re-engineer the human body.
Simulations allow more rapid testing of much larger combinations of conditions. For human bodies simulations will allow testing of drugs and other treatments without need for the huge sums of money used in real human trials and also without the need to wait for lots of real wall clock time to go by. Plus, simulations can check out dangerous scenarios that would be far too risky to try with real humans.
An increasing portion of all biomedical research and development will take place in simulations. The cost of computing will continue to decline as the software becomes more complex and the data from real lab experiments feed in to make the models increasingly more realistic.
The simulation can predict the behavior of actual human cells.
In a report in the Proceedings of the National Academy of Sciences (PNAS) made available on the journal's website on Jan. 29, the UCSD researchers led by Bernhard Ø Palsson, a professor of bioengineering in the Jacobs School of Engineering, unveiled the BiGG (biochemically, genetically, and genomically structured) database as the end product of this phase of the research project.
Each person's metabolism, which represents the conversion of food sources into energy and the assembly of molecules, is determined by genetics, environment, and nutrition. In a demonstration of the power and flexibility of the BiGG database, the UCSD researchers conducted 288 simulations, including the synthesis of testosterone and estrogen, as well as the metabolism of dietary fat. In every case, the behavior of the model matched the published performance of human cells in defined conditions.
This simulation is limited to known interactions and transformations done by cellular components. As more interactions become discovered and characterized these additional pieces of the puzzle can get added to existing simulations such as this one at UCSD. Fortunately, biochips which measure proteins and genes keep getting more powerful. For example, see my post Chip Measures Protein Binding Energies In Parallel
To accelerate the pace of biological research we need automation and miniaturization to drive down costs. The development of miniature silicon devices that can measure biological systems with a high degree of parallelism is going to drive down costs by orders of magnitude just as happened in the computer industry. The trend toward labs on a chip continues to accelerate. In a recent example of this trend Stanford microfluidics researcher Stephen Quake and collaborator Sebastian Maerkl have developed a silicon chip that can measure the affinity of transcript factor proteins (which regulate gene expression) for sections of DNA with simultaneous measurements of 2400 pairs of proteins and DNA fragments.
To understand complex biological systems and predict their behavior under particular circumstances, it is essential to characterize molecular interactions in a quantitative way, Quake said. Binding energy-the energy with which one protein bind to another or to DNA-is one important quantitative measurement researchers would like to know. But these interactions are highly transient and often involve extremely low binding affinities, so they are difficult to measure on a large scale. To overcome this hurdle, Quake and Maerkl set out to develop a microlaboratory that could trap a type of protein known as a transcription factor. Once the transcription factor was trapped, the scientists hoped to measure the binding energy of the transcription factor bound to specific DNA sequences.
But simply measuring the binding energy between a transcription factor and a single DNA sequence is not enough, Quake said. He said it would be more meaningful to know the energy involved in a transcription factor binding to many different DNA sequences. This would give researchers a more complete picture of the “DNA binding energy landscape” of each transcription factor.
To determine the binding energy landscape, Quake and Maerkl's microlaboratory needed to conduct thousands of binding-energy experiments at once. The apparatus they created, which they called mechanically induced trapping of molecular interactions (MITOMI), consists of 2,400 individual reaction chambers, each controlled by two valves and including a button membrane. Each of the chambers is less than a nanoliter in volume. That's one-billionth of a liter—enough to hold a snippet of human hair only as long as the hair's diameter. The MITOMI apparatus fits over a 2,400-unit DNA microarray, or gene chip, onto which the researchers can dab minute amounts of DNA sequences. Each spot of DNA is then enclosed in its own reaction chamber.
Quake wants to use this approach to map all the protein-protein binding energies of a single organism. The ability to use semiconductor industry manufacturing processes to cheaply mass produce silicon chips will make this possible.
The ability to conduct many measurements cheaply and in parallel will eventually enable the use of simulations to carry out much biological research. The measurements of biological phenomena made by silicon chips will serve as useful data to feed into computer simulations.
According to Quake, MITOMI brings scientists closer to an important goal. “To test theories of systems biology, we should now be able to predict biology without making any measurements on the organism itself,” he said.
Technologies from the computer industry are accelerating the rate of advance of biomedical science. This trend is why I expect the defeat of almost all diseases in the lifetimes of some people who are already alive. Technologies to achieve full body rejuvenation will even stop the process of aging.
One of the makers of these new gene chips, San Diego-based Illumina, is now looking ahead to the next phase of medical genetics. The company has recently acquired new diagnostic and sequencing technologies, which it plans to use to better identify medically relevant genes. Ultimately, the goal is to diagnose risk of specific diseases and identify the best treatment options for certain patients.
The Illumina chip contains 650,000 short sequences of DNA that can identify SNPs (single nucleotide polymorphisms), carefully selected from a map of human genetic variation known as the HapMap (see "A New Map for Health"). Each SNP represents a spot of the genome that frequently varies among individuals and acts as a signpost for that genomic region. Scientists use the chip to search for genetic variants that are more common in a group of people with the disease of interest.
This chip illustrates why the application of computer industry semiconductor process technologies to biology are so going to lower the cost of doing biological research and biomedical testing and treatment. The computer industry has developed technology to produce chips in bulk at low and declining cost.
Initially these chips will be used for research. Their lower costs will speed up the search for the meaning of genetic variations. Same sized research budgets will produce more genetic testing results each year as gene chip prices fall. Already the ability to look at 650,000 genetic variations in a single person with a single chip is going to cause a huge increase in the rate of genetic testing.
As these chips help scientists discover the significance of an increasing number of genetic variations the result will be discovery of variations whose existence becomes useful for each individual to know. For example, prospective parents wanting a particular eye or hair color or facial shape will be able to use gene chips to do pre-implantation genetic diagnosis (PGD or PIGD) on embryos fertilized in a lab (in vitro fertilization or IVF).
As soon as SNPs (single nucleotide polymorphisms or single letter differences in genetic code) are discovered for facial features, hair texture, hair and eye color, height, musculature, intelligence, and other attributes the use of gene chips to test for these attributes in embryos will explode. We could be 5 years away from the start of extensive genetic testing of embryos.
A Stanford team says the reading device of their genetic chip design could fit in a shoe box.
Stanford researchers have integrated an array of tiny magnetic sensors into a silicon chip containing circuitry that reads the sensor data. The magnetic biochip could offer an alternative to existing bioanalysis tools, which are costly and bulky.
"The magnetic chip and its reader can be made portable, into a system the size of a shoebox," says Shan Wang, professor of materials science and electrical engineering at Stanford University, in Palo Alto, CA. Its small size, he says, could make it useful at airports for detecting toxins, such as anthrax, and at crime scenes for DNA analysis.
Reductions in the size of genetic testing equipment also reduce the ability of governments to regulate the use of genetic testing. Want to ban genetic testing of employees and prospective employees? Kinda hard to do if a device the size of a shoe box can let you test dandruff flakes or hair droppings from a job interviewee. Easily find out whether the guy or gal has genetic variations associated with greater honesty or a greater proclivity to steal. Throw in the identification of some genetic variations that affect level of work motivation and lots of smaller employers especially will do secret genetic testing of job prospects.
If some governments try to ban genetic testing of embryos expect to see other countries keep embryo genetic testing unregulated. Then watch how a lot more babies get conceived on "vacations" to Caribbean islands or other countries that see big profits in medical tourism. Then for that fraction of the human race which embraces gene testing of embryos the rate of evolution will skyrocket. Anyone who doesn't jump on this will find their offspring left behind in the job market.
One-third of the engineers at MIT now work on biological problems, according to Graham C. Walker, MIT biology professor. Yet it can be challenging for biology and engineering students to understand each other.
The divide, deeper than mere semantics, can touch on basic cultural differences, he says. "Even among top-level scientists, our fundamental ways of conducting inquiry differ, depending on our interests and training."
Teaching introductory biology to MIT undergraduates, Walker experiences the disciplinary disconnect firsthand. "It's a constant challenge," he says, "to find ways to make biology comprehensible and relevant to students who think like engineers."
Professor Walker has a $1 million grant from the Howard Hughes Medical Institute to figure out better ways to teach biology to engineers. MIT now has a biological engineering degree program. These are signs of the times.
Biology used to advance at a snail's pace because its tools were so primitive. The influx of talent from semiconductor engineering and other engineering disciplines has greatly sped up the rate of progress in the field and promises to speed it up by orders of magnitude in the future. The field of microfluidics chases the idea of highly automated and cheap labs on a chip.
Imagine a chip made using semiconductor processes that has lots of reaction vessels and miniature tubes and valves, all digitally controllable. No more pipettes. No petri dishes. No lab techs making mistakes from the tedium. Software will be able to carry out long experimental sequences. Computer programs with limited domain-specific artificial intelligence will even be able to generate hypotheses and carry out experiments. That's where the world of biology is going.
Pure simulation is also going to play a larger role in biological research. Rather than use real cells and real organisms an increasing fraction of biological research will take place in computer simulations using math and known rules of behavior of biological components and systems. The faster the computers become the more of all biological research will become doable in mathematical models written in software.
Advances in instrumentation are accelerating the rate at which scientists can do experiments.
WEST LAFAYETTE, Ind. — Purdue University researchers have developed a biochip that measures the electrical activities of cells and is capable of obtaining 60 times more data in just one reading than is possible with current technology.
In the near term, the biochip could speed scientific research, which could accelerate drug development for muscle and nerve disorders like epilepsy and help create more productive crop varieties.
"Instead of doing one experiment per day, as is often the case, this technology is automated and capable of performing hundreds of experiments in one day," said Marshall Porterfield, a professor of agricultural and biological engineering who leads the team developing the chip.
The device works by measuring the concentration of ions — tiny charged particles — as they enter and exit cells. The chip can record these concentrations in up to 16 living cells temporarily sealed within fluid-filled pores in the microchip. With four electrodes per cell, the chip delivers 64 simultaneous, continuous sources of data.
This additional data allows for a deeper understanding of cellular activity compared to current technology, which measures only one point outside one cell and cannot record simultaneously, Porterfield said. The chip also directly records ion concentrations without harming the cells, whereas present methods cannot directly detect specific ions, and cells being studied typically are destroyed in the process, he said. There are several advantages to retaining live cells, he said, such as being able to conduct additional tests or monitor them as they grow.
One (I think mistaken) argument made against the practicality of pursuing Aubrey de Grey's SENS (Strategies for Engineered Negligible Senescence) proposal to reverse aging is that the problems we need to solve in order to reverse aging won't become solvable in the next few decades. Specifically, one group of critics recently argued that a rate of biotechnological advance that is faster than the semiconductor industry's Moore's Law would be required in order to solve the problems needed to reverse the aging process within the lifetimes of people currently alive. But I think these critics are missing an obvious reason why biotechnology can advance more rapidly than computer semiconductor technology.
The biochip reported above is able to speed up the collection of cellular metabolic information with a leap forward that is many times greater than the rate at which Intel co-founder Gordon Moore' predicted that computers would become faster. It is very important to notice why this advance was possible: The advances made in the semiconductor industry that allow manipulations at very small scales that took decades to achieve are now being harnessed to make sensors and other automated instrumentation for biological experimentation. The development of biochips which manipulate and measure matter on a small scale can therefore happen much more rapidly than semiconductor advances.
In a nutshell, we have the technology to do lots of small scale manipulations and measurements. Scientists and engineers who apply that technology to biological problems can therefore make huge leaps in the development of capabilities to study and manipulate biological systems.
The X Prize Foundation has announced the largest medical prize in modern history with the goal to speed up the development of DNA sequencing technology.
Washington D.C. (October 4, 2006) — The X PRIZE Foundation announced today the $10 million Archon X PRIZE for Genomics — A multi-million dollar incentive to create technology that can successfully map 100 human genomes in 10 days. The prize is designed to usher in a new era of personalized preventative medicine and stimulate new avenues of research and development of medical sciences.
Lots of big names have lined up in support of this prize.
On hand to help the X PRIZE Foundation make this historic announcement were some of the industries top minds representing the full landscape of this exciting new foray into biotechnology. Speakers at the press conference included Dr. J. Craig Venter, Chairman and CEO of the J Craig Venter Institute, Dr. Francis Collins, Director of the National Human Genome Research Institute, Anousheh Ansari, First Female Private Space Explorer and Co-Founder & Chairman Prodea Systems, Inc., Sharon Terry, President and CEO of the Genetic Alliance, Billy Tauzin, President and CEO of the Pharmaceutical Research and Manufacturing Association and Dr. Stewart Blusson, President of Archon Minerals. Archon Minerals is the title sponsor of the Archon X PRIZE for Genomics after a generous multi-million dollar donation by Dr. Blusson.
Some argue that cheap DNA sequencing will revolutionize medicine by making personalized treatments possible.
Rapid genome sequencing is widely regarded as the next great frontier for science and will eventually allow doctors to determine an individuals’ susceptibility to disease and even the genetic links to cancer. Mapping your genetic code is like taking an X-Ray allowing doctors to see inside your genetic past and eventually help determine your genetic future.
Only after we have access to affordable and fast genome sequencing will we be able to take advantage of the countless benefits. This technology helps us refine and perfect our knowledge and practice of preventive medical treatments and procedures. Preventing disease is the next best thing to curing disease.
The ability to compare the DNA sequences and medical histories of millions of people will lead to the identification of genetic variations that provide many different advantages. But I suspect the biggest benefit will come from identification of genetic variations that determine levels of intelligence and differences in personality.
The X Prize Foundation founder thinks the prize model will speed up medical advances.
"The X PRIZE Foundation has created a unique philanthropic prize model designed to stimulate research and accelerate development of radical breakthroughs that will benefit humanity," explains Dr. Peter H. Diamandis, Founder and Chairman of the X PRIZE Foundation. "The Archon X PRIZE for Genomics will revolutionize personalized medicine and custom medical treatment, forever changing the face of medical research and making genome sequencing affordable and available in every hospital and medical care facility in the world."
Personalized medicine will come in many forms. For example, some drugs are dangerous to a small fraction of the population and now are kept off the market because there's no way to identify who is at risk. If we all knew our DNA sequences then doctors could choose drugs that are compatible with our personal sequences and optimized for our sequences.
Preventive measures could be tailored to our indivdual risks too. If we each knew which genetic variations we have that increase or decrease our risks for various disease we could choose lifestyles that reduced some of our greatest risks. Though I have to say the potential to do this has been overstated. For some genetic risks there's not a diet or exercise program that is going to help.
Drugs tailored to our personal genetic sequences are still only going to be drugs. Risk profiles for diseases by themselves won't prevent the diseases. What we need are repair capabilities and for that we need stem cell therapies and gene therapies. Lots of DNA sequencing information will help in the development of stem cell and gene therapies. But the development of those therapies will depend more heavily on instrumentation advances in areas other than DNA sequencing.
Three teams have already signed up for the competition. VisiGen Biotechnologies, Inc. is based out of Houston, TX and is led by Susan Hardin Ph.D., 454 Life Sciences is a Connecticut based company headed up by Christopher McLeod and the third team, which is made up of the Westheimer Institute for Science and Technology, the Foundation for Applied Molecular Evolution, and Firebird Biomolecular Sciences LLC. They make their home in Gainesville, FL and Steve Benner is the team leader. Many other companies have inquired and more teams are expected to register soon.
Highly visible competition is a good thing. Lots of teams will work harder not just for money but for fame too.
Is faster DNA sequencing technology the greatest tool we need to accelerate the rate of advance of biotechnology? I do not think so. What we really need are better tools for watching how genes control each other. Conceptually what we need is a genomic debugger that lets scientists watch how each step of genetic regulation takes place. Which gene activation leads to which other genes getting activated or deactivated and by what mechanisms?
We also need faster and cheaper ways to measure methylation patterns on DNA. Methyl groups (a carbon with 3 hydrogens attached to it) get placed on the DNA double helix backbone to control which genes get turned on. DNA methylation patterns are part of a larger category of information called epigenetic state. The epigenetic state of a cell determines whether it is a liver cell or kidney cell or embyronic stem cell or other cell type.
In order to develop stem cell therapies and to grow replacement organs and other body parts we need the ability to cheaply and rapidly read and manipulate epigenetic state. Prizes which reward the development of better tools for reading and setting epigenetic state would do more to accelerate biomedical progress than prizes for faster DNA sequencing. But DNA sequencing is easier to describe and has gotten far more publicity.
Some experts foresee a medical revolution if the cost of DNA sequencing could be brought down low enough that a person’s genome could be decoded as part of routine treatment. Several companies have developed novel methods of sequencing, with the eventual goal of decoding a human genome for as little as $10,000.
The X Prize Foundation has not yet determined a critical parameter of its prize, that of how complete the genomes need to be. The present “complete” human genome has many gaps and is only as complete as present technology can make it.
The prize needs criteria on how to check the error rate of sequencing and also what percentage of the genome has to be sequenced. Some parts of the genome are extremely hard to sequence and also have little value. So it does not make sense to require contestants to sequence those parts.
Thanks to Methuselah Mouse Prize co-founder David Gobel for the heads-up on this announcement.
Researchers have developed a device that uses 55,000 perfectly aligned, microscopic pens to write patterns with features the size of viruses. The tool could allow researchers to study the behavior of cells at a new rate of speed and level of detail, potentially leading to better diagnostics and treatments for diseases such as cancer.
The device builds on a technique called dip-pen nanolithography, which was first developed in 1999 by Chad Mirkin, professor of chemistry, medicine, and materials science and engineering at Northwestern University. In that system, the tip of a single atomic force microscope (AFM) probe is dipped in selected molecules, much as a quill pen would be dipped in ink. Then the molecules slip from the tip of the probe onto a surface, forming lines or dots less than 100 nanometers wide. Their size is controlled by the speed of the pen.
Because it operates at room temperature, the dip-pen tool is particularly useful for working with biological materials, such as proteins and segments of DNA that would be damaged by high-energy methods like electron beam lithography.
Both biological research and computing will benefit from this device.
"This development should lead to massively miniaturized gene chips, combinatorial libraries for screening pharmaceutically active materials and new ways of fabricating and integrating nanoscale or even molecular-scale components for electronics and computers," said Chad A. Mirkin, director of Northwestern's International Institute for Nanotechnology and George B. Rathmann Professor of Chemistry, who led the research.
"In addition, it could lead to new ways of studying biological systems at the single particle level, which is important for understanding how cancer cells and viruses work and for getting them to stop what they do," he said. "Essentially one can build an entire gene or protein chip that fits underneath a single cell."
The rate of advance of biological research and biotechnology is increasingly driven by technology developed in the semiconductor industry. The technological trends that make computer power increase so rapidly are increasingly driving an acceleration of the rate at which biotechnology advances.
The OSU scientists, in collaboration with Molecular Probes-Invitrogen of Eugene, Ore., found a chemical process to directly see and visualize "superoxide" in actual cells. This oxidant, which was first discovered 80 years ago, plays a key role in both normal biological processes and – when it accumulates to excess – the destruction or death of cells and various disease processes.
"In the past, our techniques for measuring or understanding superoxide were like blindly hitting a box with a hammer and waiting for a reaction," said Joseph Beckman, a professor of biochemistry and director of the OSU Environmental Health Sciences Center. "Now we can really see and measure, in real time, what's going on in a cell as we perform various experiments."
This technique allowed them to learn in 3 months as much as they did in the previous 15 years. So that's a factor of 60 speed up in the rate at which they can figure out certain aspects of how cells work.
In research on amyotrophic lateral sclerosis, or Lou Gehrig's Disease, which is one of his lab's areas of emphasis, Beckman said they have used the new technique to learn as much in the past three months about the basic cell processes as they did in the previous 15 years. Hundreds of experiments can now rapidly be done that previously would have taken much longer or been impossible.
Theories of aging causes which cast the mitochondrion as a sort of Achilles Heel will be testable using this new method of measuring superoxide.
"This will enable labs all over the world to significantly speed up their work on the basic causes and processes of many diseases, including ALS, arthritis, diabetes, Parkinson's disease, Alzheimer's disease, heart disease and others," Beckman said. "And it should be especially useful in studying aging, particularly the theory that one cause of aging is mitochondrial decay."
The rate of advance of biological science and biotechnology is accelerating. Previously untestable hypotheses are becoming testable. Previously highly time-consuming methods of measurement are being replaced with faster, cheaper, and more automated methods of measurement as new sensors and new assays are developed. This is why I'm optimistic that many who are alive today will live to see the defeat of aging.