Updated "Longest Synthetic DNA" Plot

Carlson_longest_sdna_nov_07With the reported completion of a 580 kB piece of DNA by Venter and colleagues, it is time to update another metric of progress in biological technologies.  Assuming the report is true, it provides evidence that the technological ability to assemble large pieces of DNA from the short oligonucleotides produced by DNA synthesizers is keeping up with the productivity enhancements enabled by those synthesizers (see my prior post "Updated, Um, Carlson Curve for DNA Synthesis Productivity").  That said, this is an accomplishment of art and science, not of commerce and engineering.  The methods are esoteric and neither widespread nor sufficiently low cost to become widespread.

The news report itself is a couple of months old now.  It yet to be confirmed by scientific publication of results, so I am breaking my habit of waiting until I can see the details of the paper before including another point on the plot.  Perhaps I just need something to do as a break from writing my book.

In any event, in the 6 October, 2007 edition of The Guardian, Ed Pilkington reported, "I am creating artificial life, declares US gene pioneer":

The Guardian can reveal that a team of 20 top scientists assembled by Mr Venter, led by the Nobel laureate Hamilton Smith, has already constructed a synthetic chromosome, a feat of virtuoso bio-engineering never previously achieved. Using lab-made chemicals, they have painstakingly stitched together a chromosome that is 381 genes long and contains 580,000 base pairs of genetic code.

It does not appear, from Mr. Pilkington's story, that Venter et al have yet inserted this mammoth piece of DNA into a cell.  Though Craig Venter is supposedly "100% confident" they can accomplish this, and as a result will boot up a wholly artificial genome running a semi-artificial organism; "The new life form will depend for its ability to replicate itself and metabolise on the molecular machinery of the cell into which it has been injected, and in that sense it will not be a wholly synthetic life form."

The Guardian story includes a comment from the dependably well-spoken Pat Mooney, director of the ETC Group.  Says Mooney,  "Governments, and society in general, is way behind the ball. This is a wake-up call - what does it mean to create new life forms in a test-tube?"

Here is an open letter to Mr. Mooney:

Dear Pat,

It doesn't mean a damn thing.  Except that it helps you raise more money by scaring more people unnecessarily, so that you can go on to scare yet more people.  Have fun with that.

Best Regards,

Rob Carlson

PS Great business model. 

I just can't get really excited about 580 kB of synthetic DNA.  First, while interesting technically, the result is entirely expected.  People keep saying to me that it is really hard to manipulate large pieces of DNA in the lab, and to this I say many things we do are really hard.  Besides, nature has been manipulating large pieces of DNA very successfully for a while now.  Say, three billion years, give or take.  It was inevitable we would learn how to do it. 

Second, I know of a few individuals who are concerned that, because there is insufficient funding for this sort of work, Venter and his crew will now have some sort of lock on the IP for building new organisms.  But it is so very early in this technological game that putting money on the first demonstrated methodology is just silly.  Someone else, probably many different someones, will soon demonstrate alternatives.  Besides, how many times are we going to need to assemble 580,000 bases and 381 genes from scratch?  The capability isn't really that useful, and I don't see that it will become useful anytime soon.

The more interesting numbers are, say, 10-50 genes and 10,00-50,000 bases.  This is the size of a genetic program or circuit that will have interesting economic value for many decades to come.  But while assembling synthetic constructs (plasmids) this size is still not trivial, it is definitely old news.  The question is how will the cost for constructs of this size fall, and when can I have that DNA in days or hours instead of weeks?  And how soon before I can have a desktop box that prints synthetic DNA of this length?  As I have previously noted in this space, there is clear demand for this sort of box, which means that it will happen sooner or later.  Probably sooner. 

Third, the philosophical implications of constructing an artificial genome are overblown, in my humble opinion.   It is interesting to see that it works, to be sure.  But the notion that this demonstrates a blow against vitalism, or against other religious conceptions of life is, for me, just overexcitement.  Venter and crew have managed to chemically synthesize a long polymer, a polymer biologically indistinguishable from naturally occurring DNA; so what?  If that polymer runs a cell the same way natural DNA does, as we already knew that it would, so what?  Over the last several millennia religious doctrine has shown itself to be an extremely flexible meme, accommodating dramatic changes in human understanding of natural phenomena.  The earth is flat!  Oh, wait, no problem.  The earth is at the center of the universe!  No?  Okay, we can deal with that.  Evolution is just another Theory!  Bacteria evolve to escape antibiotics?  Okay, God's will.  No problem. I can't imagine it will be any different this time around.

Finally, it is worth asking what, if any, implications there are for the regulatory environment.  The Guardian suggests, "Mr Venter believes designer genomes have enormous positive potential if properly regulated."  This is interesting, especially given Venter's comments last winter at the initial public discussion of "Synthetic Genomics: Options for Governance".  I don't know if his comments are on record anywhere, or whether my own public comments are for that matter, but Venter basically said "Good luck with regulation," and "Fear is no basis for public policy."  In this context, I think it is interesting that Venter is not among the authors of the report.

I just finished writing my own response to "Options for Governance" for my book.  I can't say I am enthusiastic about the authors' conclusions.  The  authors purport to only present "options".  But because they examine only additional regulation, and do not examine the the policy or economic implications of maintaining the status quo, they in effect recommend regulation.  One of the authors responded to my concerns of the implicit recommendation of regulation with, "This was an oversight."  Pretty damn big oversight.

Today's news provides yet another example of the futility of regulating technologies to putatively improve security.  Despite all the economic sanctions against Iran, despite export restrictions on computer hardware, scientists and engineers in Iran report that they have constructed a modest supercomputer using electronic components sold by AMD.  Here is the story at ITNews (originally via Slashdot).  Okay, so the Iranians only have the ability to run relatively simple weather forecasting software, and it may (may!) be true that export restrictions have kept them from assembling more sophisticated, faster supercomputers. (I have to ask at this point, why would they bother?  They are rolling in dollars.  Why not just pay somebody who has a faster machine to do the weather forecasting for you?  It suggests to me that they have pulled the curtain not from their best machine, but rather from one used to be used for weapons design and is now gathering dust because they have already built a faster one.)  Extending this security model to biological technologies will be even less successful.

Export restrictions for biological components are already completely full of holes, as anyone who has applied for an account at a company selling reagents will know.  Step 1: Get a business license.  Step 2: Apply for account.  Step 3: Receive reagents in mail.  (If you are in a hurry, skip Step 1; there is always someone who doesn't bother to ask for it anyway.)  This particular security measure is just laughable, and all the more so because any attempt to really enforce the legal restrictions on reselling or shipping reagents would involve intrusive and insanely expensive physical measures that would also completely crimp legitimate domestic sales.  I can only imagine that the Iranians exploited a similar loophole to get their AMD processors, and whatever other hardware they needed.

Well, enough of that.  I have one more chapter to write before I send the book off to reviewers.  Best get to it.