October 24, 2002
Rate Of Biotech Medicine Advance Accelerating

This rate of new product development will increase even further as the ability to manipulate genes increases. Advances in the power of the technological tools will lower the cost of new product development and enable new types of products to be developed:

A record number of biotech medicines has reached the final stage of clinical trials, positioning the industry to produce as many products in the next few years as it has during the past 20.

Data compiled by the Pharmaceutical Research and Manufacturers of America show that of 371 biotech medicines now undergoing commercial tests, 116 have reached Phase III clinical trials -- the last step before the U.S. Food and Drug Administration decides whether they are safe and effective enough to sell to consumers.

This is the original press release from the Pharmaceutical Research and Manufacturers of America that probably inspired the San Francisco Chronicle article:

371 Biotechnology Medicines IN Testing Offer Hope of New Treatments for Nearly 200 Diseases

October 21, 2002


Washington, D.C. – More than 250 million people have already benefited from medicines and vaccines developed through biotechnology, and a new survey by the Pharmaceutical Research and Manufacturers of America (PhRMA) identifies 371 more biotechnology medicines in the pipeline. Nearly 200 diseases are being targeted by this research conducted by 144 companies and the National Cancer Institute.

These new medicines – all of which are in human clinical trials or are awaiting FDA approval –include 178 new medicines for cancer, 47 for infectious diseases, 26 for autoimmune diseases, 22 for neurologic disorders, and 21 for HIV/AIDS and related conditions.

Approved biotechnology medicines already treat or help prevent heart attacks, stroke, multiple sclerosis, leukemia, hepatitis, rheumatoid arthritis, breast cancer, diabetes, congestive heart failure, lymphoma, kidney cancer, cystic fibrosis and other diseases.

"These medicines are the result of extensive efforts to understand the human genome and penetrate the molecular basis of disease," said PhRMA President Alan F. Holmer. "The cutting-edge medicines in development – many of which attack or prevent disease in fundamentally different ways – offer hope to patients with diseases for which we have no cures."

Among the new biotechnology medicines in development are an epidermal growth factor inhibitor that targets and blocks signaling pathways used to promote the growth and survival of cancer cells; monoclonal antibodies – or laboratory-made versions of one of the body’s own weapons against disease – that target asthma, Crohn’s disease, rheumatoid arthritis, lupus, various types of cancer, and other diseases; and therapeutic vaccines, designed to jump start the immune system to fight such diseases as AIDS, diabetes, and several types of cancer.

Researchers are also pursuing antisense medicines – which interfere with the signaling process that triggers disease pathways for AIDS, several types of cancer, Crohn’s disease, heart disease, and psoriasis, and gene therapies, which augment normal gene functions or replace or inactivate disease-causing genes, for hemophilia, several cancers, cystic fibrosis, heart disease, and other diseases.

PhRMA represents the country’s leading research-based pharmaceutical and biotechnology companies, which are devoted to inventing medicines that allow patients to live longer, healthier, and more productive lives. The industry invested more than $30 billion in 2001 in discovering and developing new medicines. PhRMA companies are leading the way in the search for new cures.

Posted by Randall Parker at 12:19 PM
October 21, 2002
Gene Vaccines Accelerating Vaccine Development

The article discusses why gene vaccines are cheaper, faster to develop, usable for more purposes, and capable of being delivered in more ways than standard vaccines. Gene vaccines may even help slow aging:

Gene vaccines hold special promise as weapons against diseases too complex or dangerous for traditional immunology. Already, they've proven successful in hundreds of animal trials against bioweapons like anthrax and the plague, as well as against pandemics like malaria and TB, which claim millions of lives each year. In July, Oxford scientist Adrian Hill began testing a gene-based malaria vaccine on hundreds of at-risk people in Gambia.

Closer to home, a gene vaccine against melanoma has completed three rounds of clinical trials on humans and appears ready to be submitted to the FDA for final approval. When injected directly into cancerous tumors, the vaccine, called Allovectin-7, causes proteins to grow on the tumor's surface — which in turn stimulates the immune system. The drug's manufacturer, Vical, is reviewing data from the experiments in hopes of presenting them to the FDA.

Posted by Randall Parker at 11:34 AM
October 19, 2002
Keeping Brain Cells Alive Longer In Vitro

Imagine scaling this up to an even longer period of time and even more cells. Eventually they'll have the ability to keep Spock's brain alive:

A way of keeping slices of living brain tissue alive for weeks has developed by a biotech company. This will allow drug developers to study the effect of chemicals on entire neural networks, not just individual cells.

"We are building stripped-down mini-brains, if you will, directly on a chip," says Miro Pastrnak, business development director of Tensor Biosciences of Irvine, California.

Posted by Randall Parker at 06:00 PM
October 11, 2002
Personal DNA Sequencing Affordability

This article projects it will take at least 5 years before personal DNA sequencing is affordable:

US Genomics in Massachusetts has developed a machine that scans a single DNA molecule 200,000 bases long in milliseconds. For now, it untangles the DNA and scans the molecule by picking out fluorescent tags located every 1000 base pairs or so.

But chief executive Eugene Chan says the company expects to be able to read sequences one base at a time in three or four years. "Our goal is to sequence the genome instantaneously," he says.

Blonde or brunette

Other firms, such as Texas-based VisiGen Biotechnologies and British company Solexa of Essex are also trying the single-molecule approach. The consensus is that it will take at least five years before sequencing technology reaches the point where it's fast and cheap enough to make personal genomics feasible. What's more, it also has to be highly accurate.

You can find my previous post about Solexa here and one about nanopore technology for rapid DNA sequencing here. Also, once personal DNA sequencing becomes cheap the mating dance will change. and also personal DNA privacy will become impossible to protect.

Posted by Randall Parker at 07:43 PM
October 10, 2002
Microtiter Plates Next DNA Sequencing Cost Reduction?

Genome Therapeutics Corp. has won an NIH grant to try to reduce DNA sequencing costs by an order of magnitude:

Reflecting a commitment to delivering high-quality genomics services, the commercial services division of Genome Therapeutics Corp. (Nasdaq: GENE), GenomeVision(TM) Services, has received a $1.6 million grant from the National Human Genome Research Institute (NHGRI) for the advanced development of genomic technologies. As the only commercial sequencing center in the federally-funded Human Genome Project and a major participant in the Rat Genome Project, GenomeVision Services has continually worked to advance its own technologies and practices in order to help streamline critical parts of the genome sequencing process, such as sample preparation and DNA analysis.

This is a refinement of current techniques:

The goal of this two-year grant, which is separate from previous awards from the NHGRI, is to achieve a five to ten-fold reduction in the sequencing costs for large-scale genomic sequencing projects. Specifically, GenomeVision Services is working to reduce the minimum amount of DNA needed, from microliters to nanoliters, for standard instruments to perform analysis using microtiter plates. In addition to plates that use smaller sample amounts, GenomeVision Services is also developing plates that allow the removal of contaminants while still enabling the retrieval of the DNA in the sample for additional analysis. Genome Therapeutics retains all rights to the microtiter plates, which are available for licensing.

Posted by Randall Parker at 02:18 PM
September 23, 2002
UK Start-up: Your genetic code in a day

The company's name is Solexa:

A British company says it is close to perfecting a gene sequencing method that could "read" someone's genome in a day.

From Solexa's web site:

Solexa was established in 1998 to develop and commercialize a revolutionary new nanotechnology, called the Single Molecule Array™, that allows simultaneous analysis of hundreds of millions of individual molecules.

We are applying this technology to develop a method for complete personal genome sequencing, called TotalGenotyping™. This will overcome the cost and throughput bottlenecks in the production and application of individual genetic variation data that are holding back the benefits to medicine that can flow from the genome revolution. Solexa’s technology will offer a potential five order of magnitude efficiency improvement, well beyond the range possible from existing technologies.

Our technical approach combines proprietary advances in synthetic chemistry, surface chemistry, molecular biology, enzymology, array technology and optics. Based on Single Molecule Arrays with the equivalent of hundreds of millions of sequencing lanes, we will deliver base-by-base sequencing on a chip without any need for amplification of the DNA sample.

To date we have raised over £15 million (€22 million; $23 million) in venture capital investment that has enabled us to make rapid progress with the development of our technologies. We have attracted a talented and multidisciplinary team of scientists to accelerate prototype development.

Solexa occupies its own customized 14,000 sq ft facilities in Cambridge, UK.

You can also find more on their technology here.

Posted by Randall Parker at 12:31 PM
Venter: Personal DNA sequencing $1000 in 10 years

Sounds like Craig Venter is expanding The Institute for Genomic Research to develop faster DNA sequencing machines:

And you expect to be able to get that cost down to $1,000?

That’s the goal.

How far off is that?

Somebody could make a discovery tomorrow, and it could be a year from now -- or it could take 20 years.

If you take the extrapolation of the 15 to 20 years of the public genome project and $5 billion, to Celera doing it for less than $100 million in nine months, to within this year, we’d be able to sequence the essential components of your genome in less than a week for about a half-million dollars.

If you extrapolate from that curve, it’s totally reasonable to expect with new technology development within five years, we should be there. I’ve given it a margin of five to 10 years.

However, he's still denying the obvious link between genes and personality types. Oh well, doesn't matter. Lots of neurobiologists are chasing down those links.

Posted by Randall Parker at 11:10 AM
September 04, 2002
Nanopore technology: sequence your DNA in two hours!

Current DNA sequencing techniques involve taking the DNA from a person or other organism and then making billions of copies of it to run thru sequencing machines. This is slow, expensive, and error prone. Back in 1989 UCSC professor David Deamer first conceived of the idea of making nanopores thru which a single strand of DNA would pass at a time and as the strand passed thru the nanopore its changing electrical pattern would be used to read each successive DNA base (each letter location in the genetic code) via sensors built into the nanopore structure. This approach holds the potential of allowing for miniaturization, elimination of lots of expensive reagents, and to speed sequencing by many orders of magnitude.

One of the teams attempting to develop nanopore DNA sequencing technology is at Harvard. From Harvard Biology Professor Daniel Branton's home page:

A novel technology for probing, and eventually sequencing, individual DNA molecules using single-channel recording techniques has been conceived. Single molecules of DNA are drawn through a small channel or nanopore that functions as a sensitive detector. The detection schemes being developed will transduce the different chemical and physical properties of each base into a characteristic electronic signal. Nanopore sequencing has the potential of reading very long stretches of DNA at rates exceeding 1 base per millisecond.

Biophysics Ph.D. candidate Lucas Nivon, who works in the lab of Professor Dan Branton has this to say about the potential for nanopore technology:

Professors Dan Branton and David Deamer developed a new way to sequence single-stranded DNA by running it through a protein nanopore. Using this method, we could potentially sequence a human genome in 2 hours.

Well, 1 base per millisecond translates into 86 million bases per day. With a 2.9 billion size human genome it would take slightly over a month to sequence an entire genome. But Nivon's 2 hour estimate is plausible because many nanopores could be placed into a single device. With 500 nanopores in a single device the human genome could be decoded in less than 2 hours. The first article in the list below uses the 500 nanopore example though they quote a 24 to 48 hour sequencing time. Possibly different generations of this technology are being referenced to come out with different predicted sequencing times.

For a more detailed discussion of this topic see these articles:

Posted by Randall Parker at 12:16 PM
August 31, 2002
Will biological technologies advance as rapidly as electronic technologies?

How fast will biotechnology advance? Will it be extremely difficult and time consuming to discover the genetic causes of various human characteristics or the genetic variations that contribute to disease? We will start by taking a look at some of the known rates of technological advance in the electronics industry. Then we'll look at biotech and see if we can find similar rates of advance in crucial biotechnologies.

In the electronics industry it is well known that microprocessor speed doubles about every 18 months. Intel co-founder Gordon Moore in 1965 famously stated Moore's Law (more about it here) which predicted a microprocessor speed doubling rate that would last for decades. He originally predicted a 1 year doubling rate. But the rate of progress slowed to an 18 month doubling rate in the late 1970s. Gordon Moore is now predicting that in a few generations the microprocessor speed doubling rate will slow to a three year interval.

While the microprocessor speed doubling rate has attracted the most attention in the popular press there are other electronics technology doubling rates that are of equal or greater importance. Two big ones are hard disk storage capacity and fiber optic transmission bandwidth. In contrast to Moore's Law for microprocessor speed the hard disk storage doubling rate has actually accelerated in recent years:

Throughout the 1970s and '80s, bit density increased at a compounded rate of about 25 percent per year (which implies a doubling time of roughly three years). After 1991 the annual growth rate jumped to 60 percent (an 18-month doubling time), and after 1997 to 100 percent (a one-year doubling time).

Fiber optic capacity is doubling at an even faster rate. The number of pulses per laser is doubling once every 18 months while the number of laser frequencies per optical fiber is doubling once every 12 months. So in 3 years we can expect the transmission capacity of a single fiber optic to go thru 5 doublings which translates into a 32 times increase in capacity per fiber. The combination of increase in number of lasers and increase in amount of information sent per laser yields a doubling period is less than 8 months. This is an astounding rate of progress.

So what does all of this have to do with the future of biotechnology? Well, certainly computers and computer networks are vital for doing biological research and biotech development work. So biology will advance more rapidly in the future than it has in the past because technologies that are useful as supporting tools but which are not specific to doing biology are advancing so rapidly. But what is more interesting is progress of various technologies that are specific to trying to understand and manipulate biological systems. While what follows is far from a complete picture of biotech rates of advance even this partial picture makes clear that we can expect revolutionary advances in biotechnology within the lifetimes of most of us.

This recent article in the New York Times is about a project in Iceland to do SNP (Single Nucleotide Polymorphism - a single letter position in the genome that can vary from person to person) mapping to hunt for genetic causes of diseases. They mention that their cost of doiing each SNP position analysis is 50 cents. Okay, some scientists estimate that the number of important SNPs in humans is about 100,000 SNPs (other estimates range as high as 400,000). These are SNPs that occur in areas of the genome that get expressed. That means that if you happen to have a spare $50,000 (in US dollars) lying around you can have your own SNP map done now. Pretty pricey but literally millions of millionaires today could afford to have their SNPs mapped (hey you multimillionaires: be the first person in your social circle to know your DNA SNP map!). I will leave for a later post how we personally and collectively will be able to benefit some day from having our personal SNP maps done.

Since $50,000 is a large chunk of cash for most of us the really interesting question is this: How fast will SNP mapping costs fall? To start with, it would help to have data on how SNP mapping costs have fallen in the past. It looks like SNP mapping costs haven't fallen at all in the last 3 years. This Wired article from 1999 quotes a cost for SNP mapping of 50 cents which is the same as the price quoted in the June 2002 NY Times article. However, the Wired article claims that Glaxo's Luminex Bead Technology may eventually reduce SNP costs to one-one thousandth of a cent per SNP. So to have 100,000 SNPs checked would cost you one whole US dollar. The cost of a doctor's visit to draw the blood (or perhaps to take a skin sample) and send it into the lab would cost more than the test itself. One can imagine mass screening programs run at work places and schools as a way to drive the total cost closer to the cost of the test itself. When something like the Luminex Bead Technology makes it to market the vast bulk of the populations of the industrialized countries will be able to get their personal SNP maps done. In later posts we'll explore the many ways this information will be used.

That Wired article makes no claim as to when this huge reduction in SNP mapping costs is going to happen. But on the Cambridge Healthtech Institute site they claim that the biotech industry has targeted an achievement of 1 cent per SNP within 2 years. That would put the cost per person for SNP mapping at about $1000, or if one accepts a higher estimate of 400,000 for the number of important SNPs in the genome the total cost is $4000 per person. Quite affordable for the affluent person who really must have everything. The CHI article also cites an SNP assay system available now from Affymetrix using their gene array chip technology that lowers SNP assay costs to 30 cents per location.

Since not all DNA sequence differences are SNP differences there will still be uses for other types of DNA assaying technology. Basic sequencing of entire genomes will continue to have uses for human health and other purposes. There are advances happening in basic DNA sequencing technology as well. The Cambridge Healthtech Insitute page mentions a nanopore sequencing method that may eventually be able to sequence over 1000 DNA locations (with each location referred to as a base pair or bp) per second. That would be over 86 million bp/day per instrument which translates into the ability to sequence the entire human genome in a little over a month. Compare that to the several year time period that the human genome sequencing project took (and that used many DNA sequencing machines - anyone know how many?). In the short term they claim a 1 to 2 year industry goal to produce machines that can sequence on the order of over 1 million bp/day as compared to the current high end of 200,000-300,000 bp/day per instrument. To put this in perspective they are projecting an advance in DNA sequencing throughput in a time frame which yields a doubling rate that is faster than the Moore's Law doubling rate for microprocessors.

DNA sequencing can be thought of as a way to read structure. It doesn't by itself explain how the structure functions or when the structure is functioning in a particular way. However, advances are being made in methods for monitoring the activity level or state of each of the genes in a cell. It used to be that just measuring the activity level of a single gene was quite difficult. But there are technologies for watching gene activity as well. Affymetrix GeneChip arrays can measure the activity of tens of thousands of genes at once.

These are all signs that biotechnology is going to advance at rates which are analogous to the way electronics technology has been advancing for decades. If that is the case we should expect to see the costs for taking apart and manipulating biological systems to drop by orders of magnitude while the speed of doing so rises by orders of magnitude as well.

The lack of ability to rapidly read the contents and state of our DNA has kept molecular biology advancing for decades as a veritable snail's pace. Without easy access to the basic code that governs cells we had little prospect of ever fully understanding degenerative diseases, aging, or of how and why we differ from each other physically and mentally. But as sequencing and assaying techniques increase in speed and fall in cost the very complex biological processes within cells that have remained a mystery for most of human history are suddenly becoming accessible to dissection.

Later posts will explore the many practical uses and dangerous abuses that these advances in capability can be used for.

Posted by Randall Parker at 12:12 PM
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