synthesis

Updated, um, Carlson Curve for DNA Synthesis Productivity

It seems that productivity improvements in DNA synthesis have resumed their previous pace.  As I noted in Bio-era's Genome Synthesis and Design Futures, starting in about 2002 there was a pause in productivity improvements enabled by commercially available instruments.

According to the specs and the company reps I met at iGEM 2007, a single Febit "Geniom" synthesizer can crank out about 500,000 bases a day and requires about 30 minutes of labor per run.  It looked to me like the number should be closer to 250KB per instrument per day, so I made an executive decision and allowed that the 16 synthesizers one person could run in a day could produce 2.5 megabases of single-stranded ~40-mers per day.  This in part because there is some question about the quality of the sequences produced by the particular chemistry used in the instrument.  It was asserted by the company reps that the Geniom instruments are being adopted by major gene synthesis companies as their primary source of oligos.  Note that running all those instruments would cost you up front just under US$ 5 million, without volume discounts, for 16 of the $300,000 instruments (plus some amount for infrastructure).

The quality of the DNA becomes particularly important if you are using the single-stranded oligos produced by the synthesizer to assemble a gene length construct.  To reiterate the point, the 2.5 megabases per day consists of short, single-stranded pieces.  The cost -- labor, time, and monetary -- of assembling genes is another matter entirely.  These costs are not really possible to estimate based on publicly available information, as this sort of thing is treated as secret by firms in the synthesis business.  Given that finished genes cost about 10 times as much as oligos, and that synthesis firms are probably making a decent margin on their product, the assembly process might run 5 to 8 times the cost of the oligos, but that is totally a guess.  (Here is a link to a ZIP file containing some of the graphics from the Bio-era report, including cost curves for gene and oligo synthesis.)

One final note: the Febit reps suggested they are selling instruments in part based on IP concerns of customers.  That is, a number of their customers are sufficiently concerned about releasing designs for expression chips and oligo sets -- even to contract manufacturers under confidentiality agreements -- that they are forking over $300,000 per instrument to maintain their IP security.  This is something I predicted in Genome Synthesis and Design Futures, though frankly I am surprised it is already happening.  Now we just have to wait for the first gene synthesis machine to show up on the market.  That will really change things. 

The Moon in HD

Super.  Duper.  Cool.

How big is the Bio-economy?

The words “biotechnology” and “biotech” are often used by the press and industry observers in limited and inconsistent ways.  Those words may be used to describe only pharmaceutical products, or in another context only the industry surrounding genetically modified plants, while in yet another context a combination of biofuels, plastics, chemicals, and plant extracts.  The total economic value of biotechnology companies is therefore difficult to assess, and it is challenging to disentangle the component of revenue due each to public and private firms.

I've managed to get a rough idea of where the money is for industrial biotech, agbiotech, and biopharmeceuticals.  Based on surveys from Nature Biotechnology, the U.S. Government, various organizations in Europe, and several private consulting firms, it appears estimates of total revenues range from US$ 80 to 150 billion annually, where the specific dollar value depends strongly on which set of products are included.  The various surveys that provide this information differ not only in their classification of companies, but also in methodology, which in the case of data summarized by private consulting firms is not always available for scrutiny.  For whatever reason, these firms tend to produce the highest estimates of total revenues.  Further complicating the situation is that results from private biotech companies are self-reported and there are no publicly available documents that can be used for independent verification.  One estimate from Nature Biotechnology, based on data from 2004 (explicitly excluding agricultural, industrial, and environmental biotech firms), suggested approximately 85% of all biotech companies are private, accounting for a bit less than 50% of employment in the sector  and 27% of revenues.

A rough summary follows:  As of 2006, biotech drugs accounted for about US$ 65 billion in sales worldwide, with about 85% of that in the U.S.  Genetically modified crops accounted for another US$ 6 billion, with industrial applications (including fuels, chemicals, materials, reagents, and services) contributing US$ 50-80 billion, depending on who is counting and how.  Annual growth rates over the last decade appear to be 15-20% for medical and industrial applications, and 10% for agricultural applications.

I am not going to go through all the details here at this time.  But the final amount is pretty interesting.  After sifting through many different sets of numbers, I estimate that revenues within the US are presently about US$125 billion, or approximately 1% of US GDP, and growing at a rate of 15-20% annually.

1% of GDP may not seem very large, but a few years ago it was only 0.5%.  At some point this torrid growth will have to slow down, but it isn't clear that this will be anytime soon.  Nor is it clear how large a fraction of GDP that biotech could ultimately be.  That is my next project.

Off to iGEM 2007

I am headed out the door to the 2007 International Genetically Engineered Machines (iGEM) Competition at MIT.  There look to be ~56 teams composed of ~400 students from around the world.  As I am a judge this year, I won't be blogging any more about it until it's over.

I have been looking forward to this for months -- it should be great fun.