The Synthetic Biology Sky Is Not Falling

    By Kevin E. Noonan --

There is something about biotechnology that brings out the Cassandras (which is being kind; "Chicken Little" is a more accurate characterization) in people who oppose it.  Whether motivated by a renewed "vitalism" (see "Science Fiction in The New York Times") or some kind of green (or Green) impulse, the temperature of the debate always seems overheated.

Jim Thomas (at right), general manager of the Erosion, Technology and Concentration (ETC) Group, a Canadian environmental group, has in the past raised the alarm against Dr. J. Craig Venter, one of the most audacious (and successful) of the 20th century breed of biotechnology scientist/entrepreneurs (see "Patenting Life (Really)").  The issue (or threat, depending on your prejudices):  Dr. Venter's attempts to produce (and patent) a synthetic microorganism.  The work is based on Mycoplasma genitalium, a bacterium whose genome encodes a mere 482 genes.  The idea is to identify a core set of essential genes by systematically subtracting genes from the organism to see which ones are required for viability.  Earlier this year, Dr. Venter's group reported that it had been able to delete 101 of those genes.  Once the set of minimal genes has been identified, they can be introduced into a bacterial "shell," and this would result for the first time in a synthetic organism that does not exist in nature.

Of course, Dr. Venter (at right) and his group has applied for patents on this organism; examples of such patent applications are published International Application Publication No. WO 2007/047148 (published April 26, 2007), and U.S. Patent Application Publication No. 2007/0122826 (published May 31, 2007).  Representative claims include:

1.  A set of protein-coding genes that provides the information required for growth and replication of a free-living organism under axenic conditions in a rich bacterial culture medium, wherein the set lacks at least 40 of the 101 protein-coding genes listed in Table 2, or functional equivalents thereof, wherein at least one of the genes in Table 4 is among the lacking genes; wherein the set comprises between 350 and 381 of the 381 protein-coding genes listed in Table 3, or functional equivalents thereof, including at least one of the genes in Table 5; and wherein the set comprises no more than 450 protein-coding genes.

20.  A free-living organism that can grow and replicate under axenic conditions in a rich bacterial culture medium, whose set of genes consists of the set of any of claims 1-15.

The claims thus encompass the specific minimal gene set itself (that defines the genetic content of the bacteria) as well as the bacteria itself.  On their face they would appear to satisfy the criteria of usefulness, novelty, and non-obviousness, and since they are directed to bacteria, they should not implicate the usual concerns voiced by those in opposition to human gene patenting.  Although a much greater technical tour de force, these claims hearken back to the distinctions drawn by the U.S. Supreme Court in deciding in Diamond v. Chakrabarty that a recombinant Pseudomonas aeruginosa bacteria was patentable.

Mr. Thomas thinks otherwise.  In a press release (which was also cited on the WIRED Science blog), he opines that "overly-broad" patent claims could "stunt" synthetic biological research.  (Interestingly WIRED characterizes ETC as a "biotech watchdog" rather than as an environmental group.)  Mr. Thomas characterizes the Venter claims as a "legal rats' nest," including claims to "basic research" such as "adding synthetic DNA to a living organism."  These sentiments are echoed by Dr. Tom Knight (at left), a computational biologist from the Massachusetts Institute of Technology, who calls the claims "absurdly, ridiculously broad" -- the piece is silent on Dr. Knight's credentials for making this assessment.  ETC's propaganda is seasoned with catchy sound bites, such as analogizing Dr. Venter's efforts with Bill Gates' allegedly predatory activities in the computer sphere, and warning that Dr. Venter is trying to create a "Microbesoft" monopoly.

Harvard geneticist (and "godfather" of the synthetic biology field) Dr. George Church (at right) once more brings some perspective and sagacity to the discussion.  He rightly notes that the claims would need to be narrowed significantly before they could be granted.  He sets forth a list of "unlikely" events that would need to occur for the horrors ETC envisions to occur:

1. Patent offices worldwide decide that the claims are useful and non-obvious without restrictions,
2. These claims are upheld in court challenges,
3. The market favors the patent holders and no work-arounds are found,
4. The resulting monopoly discourages innovation,
5. The government doesn't interfere with such a monopoly.

Dr. Church also reminds us that "even Microsoft couldn't stop Google, Firefox, Java, Linux, etc."

Something Dr. Church did not mention, and which deserves mentioning, is that it is extremely difficult to obtain the kind of broad patent claims that ETC and its sympathizers fear.  An important reason comes from the inherent complexity of biological systems and the relatively little we know about how these systems work.  "Work arounds" can be difficult in the mechanical and electrical arts, because the underlying technology can be predictable and there can in fact be one good solution to a problem that is the most efficient, economical, reliable, and compatible with existing systems.  Biology, in contrast, seems to operate on the principle that "when life closes a door, it opens a window"; in a word, living systems adapt.  Because of that, the instances of broad patent claims to fundamental biological methods, reagents, compounds, or processes are rare (and Patent Docs would appreciate our readers pointing out any such claims).  So the practical chances of Dr. Venter "stifling the field of synthetic biology" are unrealistic.  Particularly because, even if all of Dr. Church's unlikelihoods were to occur, the patent term would expire in less than twenty years, and by that time the field would have moved on using design-arounds motivated by Dr. Venter's own patent claims.

The WIRED article also quotes MIT biological engineer Dr. Drew Endy (another synthetic biology godfather; at left) as referencing one of his own papers, published in 2005 in the journal Molecular Systems Biology, "which describes the design, construction, and testing of engineered genomes . . . [e]verything described in this paper is in the public domain."  The article concludes that since the paper is in the public domain, the techniques for producing synthetic organisms cannot be hampered by anything Dr. Venter is trying to do.  This part of the article is evidence of the vast disconnect between the understanding of scientists, even eminent scientists, and patent law.  While Dr. Endy's work in his paper is important and perhaps groundbreaking, it is directed to a bacterial virus (the T7 bacteriophage), not a bacteria, and thus its relevance to the patentability of Dr. Venter's claims is tenuous at best.  It is not worth mentioning (since it seems to occur so often) that there is not a word in the WIRED article from a patent attorney on the subject.  Regardless of such an attorney's opinion on the underlying patentability of Dr. Venter's work (and patent attorneys are not monolithic on the subject; after all, Dan Ravicher of the Public Patent Foundation (PUBPAT) opposes patenting some forms of biotechnology invention), at least the article would have been more informed about the legal issues and probabilities regarding the patentability of Dr. Venter's work.  One can only speculate that what these groups want is not light but heat, in view of the vehemence of their opposition, which is as good an explanation as any for the tone and tenor of their comments.

Comments

[Frank]

Tom Knight is sporting some profoundly unserious facial hair.

That is all.