iGEM 2010: Finalists are Announced

iGEM 2010 finalists: Slovenia, Cambridge, Peking, TU Delft, BCCS-Bristol, Imperial College London. No US teams in the finals for the first time... (Drew Endy corrected my faulty memory via email to note that no US teams made it to the finals last year, either...)

The teams are starting their presentations now.

iGEM 2010: Midway

All the talks are over for this year's iGEM, with the final poster session to go and then the annual marathon judge's meeting.  Alas, there is no chromo-poo this year, but there is one team running around in wonderful light-blue leisure suits.  There are from Paris, I think.

I have been very impressed with the sophistication of the component and device design this year.  More on this after the finals tomorrow.

Of general note, Uni Freiburg Bioware biobricked a bunch of parts for packaging up therapeutics in adeno-associated viruses (AAVs).  They showed targeting toward specific cancer cell lines, and also showed the means to build various adapters to target any number of cell-specific markers. There is a very nice 150 pg manual describing protocols for design and use of the AAVs for delivering genes and pro-drugs, with an emphasis on personalized medicine.  All the sequences are online, and even if you can't get the parts from the Registry of Standard Biological parts you can have Blue Heron or somebody else synthesize them for you.  In other words, it appears that Uni Freiburg has enabled DIY Garage Therapeutics.  Got cancer?  Now you've got a personalized therapy.

This is not to say that every Tom, Dick, and Andrew Hessel will be able to generate a personalized cancer therapy on the first try.  But it steps like this gives people an opportunity to fail in a new way, which is a prerequisite to, and always precedes, success.  Failure is the first, and most important component of innovation.

And people will fail -- I am not entirely comfortable with the thought of people attempting their own therapies at home.  But I do think it is inevitable, and I don't think there is any way to stop it. That is the world we live in. 

iGEM 2010: It Begins

I'm at MIT serving as a judge for iGEM 2010.  There are about 120 teams here, and more than 1000 students and team advisers running around, project posters everywhere one looks, and three days of presentations describing various new genetic bits and pieces to come.  The Registry of Standard Biological Parts runneth over.

I'll post pictures and comments as I can, though my duties as a judge will preclude saying too much before the conclusion on Monday.

Surprise Outbreak of Common Sense in Washington DC

News today that the Justice Department has filed an amicus brief outlining a new position that naturally occurring genes should not be patentable.  The New York Times is reporting that "while the government took the plaintiffs' side on the issue of isolated DNA, it sided with Myriad on patentability of manipulated DNA."  The change in position was evidently prompted by the decision of a federal judge this past spring that certain claims in what are known as the BRCA 1/2 patents should be overturned because those genes are preexisting in nature.  Perhaps Jon Stewart has more influence in DC than we all thought.

I am largely on board with the line taken by the Justice Department.  It is pretty close to my own analysis, as described in my post from last spring: "Big Gene Patent (Busting) News???"  There are, however, a few bits that I am still chewing on, which I will get to later.

First, in broad strokes, the government's brief supports the decision of District Judge Robert Sweet that naturally occurring gene sequences are not patentable, but weighed in against Judge Sweet's analysis that DNA coding for natural genes is not patentable if it has been restructured in an artificial construct but is still the same sequence as occurs in nature.  The most obvious example of the latter is a coding sequence with all introns removed and packed in a plasmid as a cDNA.

Here is the Justice Department's language (the text of the brief is available via the NYT page):

The district court erroneously cast doubt on the patent-eligibility of a broad range of man-made compositions of matter whose value derives from the information-encoding capacity of DNA. Such compositions -- e.g., cDNAs, vectors, recombinant plasmids, and chimeric proteins, as well as countless industrial products, such as vaccines and genetically modified crops, created with the aid of such molecules -- are in every meaningful sense the fruits of human ingenuity and thus qualify as "'human-made inventions'" eligible for patent protection under section 101. (p.9)

...The district court correctly held, however, that genomic DNA that has merely been isolated from the human body, without further alteration or manipulation, is not patent-eligible. (p.10)

...Indeed, the relationship between a naturally occurring nucleotide sequence and the molecule it expresses in a human cell -- that is, the relationship between genotype and phenotype -- is simply a law of nature. (p.10)

Here is the meat:

The chemical structure of native human genes is a product of nature, and it is no less a product of nature when that structure is "isolated" from its natural environment than are cotton fibers that have been separated from cotton seeds or coal that has been extracted from the earth.

The scope of Section 101 is purposefully wide and its threshold is not difficult to cross.  See Bilski, 130 S.Ct. at 3225.  New and useful methods of identifying, isolating, extracting, or using genes and genetic information may be patented (subject to the prohibition against patenting abstract ideas), as may nearly any man-made transformation or manipulation of the raw materials of the genome, such as cDNAs. Thus, the patent laws embrace gene replacement therapies, engineered biologic drugs, methods of modifying the properties of plants or generating biofuels, and similar advanced applications of biotechnology. Crossing the threshold of section 101, however, requires something more than identifying and isolating what has always existed in nature, no matter how difficult or useful that discovery may be. (p.11)

It might seem that the Justice Department gives back a lot of power to those who hold patents on natural genes by including cDNAs (with introns removed) as patentable material.  This would seem to give patent holders a lock on the human proteins those genes encode, because the most common way to make a protein is to use a cDNA (or similar) to express a protein in a host like E. coli or yeast.  So unless people come up with a good way to cause overexpression of human proteins from native genes via mechanisms that chop out the introns -- and some methods like that do exist -- the patent seems to block use of the protein.

But I am not sure that this brief gives any succor to those hoping for patent protection of a genetic diagnostic.  Those diagnostics generally work by using a short sequence of the gene in question as a PCR primer to find (or exclude) particular sequences of clinical interest in a patient's genome.  Those primers generally can be found in regions of DNA not interrupted by an intron, or can include the intron in the primer sequence, which means that the primer can consist of sequences that were preexisting in nature.  Only if the primer has to be composed of a sequence that -- in nature -- is interrupted by an intron but is only found in somebody's edited cDNA library without that intron would a patent protect the diagnostic assay.

A penultimate thought on the brief: I am still pondering whether the Justice Department lawyers, in their extended discussion of DNA as information carrying medium, got their analysis right.  I will have to read the brief again.  And perhaps again after that.

Finally, the brief leaves most of my previous conclusions intact, namely that the biggest impact of Judge Sweet's ruling that natural sequences cannot be patented may be for work in organisms other than humans.  From my post last May:

...the rest of the biotech industry shouldn't be concerned about thisruling, frankly.  They might even celebrate the fact that they now have access, potentially, to a whole bunch more genes that are naturally occurring.  Not just in humans, mind you, but any organism.  This opens up a rather substantial toolbox for anybody interested in using biological technologies derived from viruses, bacteria, plants, etc.  If it holds up over the long run, Judge Sweet's decision should accelerate innovation.  That is definitely a good thing.

Now we wait for what the appellate court has to say.

The Economist debate on the most significant technological development of the 20th century

The Economist has just posted my invited comments on their current debate: "This house believes the development of computing was the most significant technological advance of the 20th century."

As with the last time I was invited to be a "guest speaker" (just one of the oddities of horning an Oxford-style debate into an online shoe), I have difficulty coloring between the lines.  Here are the first couple of graphs of today's contribution:

The development of computing--broadly construed--was indeed the most significant technological advance of the 20th century. New technologies, however, never crop up by themselves, but are instead part of the woven web of human endeavour. There is always more to a given technology than meets the eye.

We often oversimplify "computing" and think only of software or algorithms used to manipulate information. That information comes in units of bits, and our ability to store and crunch those bits has certainly changed our economies and societies over the past century. But those bits reside on a disk, or in a memory circuit, and the crunching of bits is done by silicon chips. Those disks, circuits and chips had to improve so that computing could advance.

Progress in building computers during the mid-20th century required first an understanding of materials and how they interact; from this knowledge, which initially lived on paper and in the minds of scientists and engineers, were built the first computer chips. As those chips increased in complexity, so did the computational power they conferred on computer designers. That computational power was used to design more powerful chips, creating a feedback loop. By the end of the century, new chips and software packages could only be designed using computers, and their complex behaviour could only be understood with the aid of computers.

The development of computing, therefore, required not just development of software but also of the ability to build the physical infrastructure that runs software and stores information. In other words, our improving ability to control atoms in the service of building computers was crucial to advancing the technology we call "computing". Advances in controlling atoms have naturally been extended to other areas of human enterprise. Computer-aided design and manufacturing have radically changed our ability to transform ideas into objects. Our manufactured world--which includes cars, aircraft, medicines, food, music, phones and even shoes--now arrives at our doorsteps as a consequence of this increase in computational power.

I go on to observe that computation is already having an effect on food through increased corn yields courtesy of gene sequencing and expression analysis.

Like so:

Biodesic_US_corn_yield.pngClick through to read the rest.

Hey look -- I have an Idea!

On my head, that is.  Not in, alas, but on.  That's the way it goes, some days.  But at least I am pressing forward.  Or the idea on my head is.  That is what the sign says, anyway. 

carlson.jpgWeek before last, I spent an enjoyable couple of days at The Economist's Ideas Economy: Human Potential 2010.  I'll post the video when it is available.

Among the most interesting things I heard: Richard Florida says that the "creative sector" has never been above 5% unemployment, and that sector now constitutes 30% of the US workforce.  Here is his presentation:

I also had the chance to meet Vivek Wadhwa (very smart fellow), whose recent fascinating blog post on whether job creation comes from big companies or startups I have been pondering for weeks.  Here is a snippet from the post: "Startups aren't just an important contributor to job growth: they're the only thing. Without startups, there would be no net job growth in the U.S. economy. From 1977 to 2005, existing companies were net job destroyers, losing 1 million net jobs per year. In contrast, new businesses in their first year added an average of 3 million jobs annually."

The differing impacts of startups and established companies on the economy and on innovation are much on my mind these last few months.  Unconventional innovation tends to come from startups, and often from garages, and as I examine in my book that is precisely where we should be looking for new biological technologies.  I've been pondering what it takes for a small company developing a biological technology to succeed in industries dominated by Goliaths.  Microbrewing provides a great existence proof of the potential.  Garage biology is here.  Hang on to your hats.