By Kevin E. Noonan —

The emotionally-charged phrase "patenting life" has been used by Michael Crichton, Lori Andrews, and others to raise the temperature on the debate over whether biotechnology patents (usually involving isolated genes) should be banned or curtailed.  Although absent from the bill introduced by Congressman
Becerra (at right) – who represents Dr. Crichton’s district – to limit gene patenting, the aim is the same:  defining compositions of matter derived from living organisms as being outside the scope of patent protection.  This effort forms part of a quasi-religious opposition to certain biologically-related technologies that can fairly be called the "new vitalism," since the only characteristic that distinguishes the objected-to subject matter is that it comes from a living thing.  This trend runs counter to more than 100 years of scientific progress, beginning with Wohler‘s demonstration that urea (produced in mammalian urine) was in fact merely a chemical compound that could be produced from non-living chemicals in a laboratory.  It also runs counter to the Federal Circuit’s pronouncement that "[a] gene is but a chemical, albeit a complex one" in Amgen Inc. v. Chugai Pharmaceutical Co.

This debate has also ensnared transgenic organisms (although not in the United States) and stem cells, although in fairness the opposition to the Wisconsin Alumni Research Foundation’s primate stem cell patents is based more on the desire to profit from stem cell development than any principled objection to the subject matter per se (see "It’s Time to Stop the Hypocrisy over Stem Cell Patents" – Part I and Part II).  Little noticed (until now) have been patents on recombinant microorganisms, especially bacteria, which have been patentable ever since the U.S. Supreme Court’s decision (5 Justices to 4) in 1980 in the

Diamond v. Chakrabarty case.  This is due, at least in part, to the fact that the Chakrabarty decision squarely addressed the patentability of recombinant bacteria in the affirmative (at left is Ananda Chakrabarty).  It is only the more expansive citation of the Congressional intent from the legislative history of 35 U.S.C. § 101 that patentability was intended to encompass "everything under the sun made by man" that has supported the wide latitude that patent law has given to biotechnology inventions.

The question of just how far the Chakrabarty decision will extend is being tested by the perennial "bad boy" of biotechnology, J. Craig Venter (at right).  Dr. Venter’s latest venture is the development of a synthetic microorganism defined by a core set of essential genes that are being defined by subtracting genes from the Mycoplasma genitalium genome, which naturally contains 482 genes (see full genome below), until viability is affected.  So far, Dr. Venter’s group has been able to delete 101 of those genes, and the intention is to take the minimal gene set, plus genes encoding a desired phenotype, and introduce them into a bacterial "shell," thus defining for the first time a synthetic organism that does not exist in nature.  Significantly, this was precisely the distinction used by the Supreme Court in deciding that Dr. Chakrabarty’s recombinant Pseudomonas aeruginosa bacteria was patentable.

And of course, the Venter group has applied for a patent, in the United States and under the auspices of the Patent Cooperation Treaty (PCT).  The PCT application has published (as International Application Publication No. WO 2007/047148, published April 26, 2007) and in the U.S. as 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.

These claims thus encompass the specific minimal gene set that defines the bacteria, as well as the bacteria itself.  These claims should be unremarkable, since they are clearly within the scope of patentability in the U.S. as defined by Section 101 as interpreted by the Supreme Court.  And they are also limited to a microorganism, and thus do not implicate the usual concerns voiced by those in opposition to human gene patenting.  They are also useful, since the minimal genome is intended to permit the bacteria to be engineered to express any number of genes necessary for a desired phenotype.

Despite this, Dr. Venter’s synthetic bacteria is causing a stir.  One example is a Canadian environmental group, the Erosion, Technology and Concentration (ETC) Group, that has issued a call for patent offices worldwide to refuse the Venter patent on the organism.  Reasons raised for this position include unspecified "far-reaching social, ethical and environmental implications."  Other statements by the group reveal that they are also concerned with what they characterize "a high-stakes commercial race to synthesise and privatise synthetic life forms."  Without support, the group also evinces a desire to "slap down bad patents," as if the very grant of a patent to Dr. Venter’s colleagues on these claims would by definition be a "bad" patent.  In addition, others have speculated (as they used to when genetic engineering was in its infancy) that Dr. Venter may be creating a "superbug" that could be used as a "bioweapon" (showing how little they understand how difficult it is to weaponize a biological agent; see Miller et al., Germs: Biological Weapons and America’s Secret War, New York: Simon & Schuster, 2001).

An unbiased reading of the specification and claims shows that what is claimed is relatively narrow, since it is limited to the M. genetalium gene complement specifically determined.  (A publication from the Venter group in 1999 is likely to preclude any broad claims, by anyone, in the area of synthetic microorganisms.)  As George Church (at right) at Harvard has noted, most researchers would prefer to use an organism like E. coli for genetic engineering research, which should not fall within the scope of Dr. Venter’s claims.  As for those who complain that the patent would stifle innovation (a rallying cry most often shouted by the "patent reform" contingent of the IT community), they forget that any patent Dr. Venter obtains would be limited to 20 years from its filing date (in this case, expiring on October 12, 2025).  It is unlikely that the science of synthetic microorganisms will have fulfilled all its present promise by then, and once in the public domain, of course, these organisms will be available for use with after-developed technology.  Paradoxically, the absence of a patent to protect these organisms will most likely preclude Dr. Venter from obtaining the funding necessary to exploit them and the benefits that Dr. Venter, and the public, would enjoy should the technology be developed.  It is ironic that those whom profess most loudly that they want to protect innovation seem so ready to take steps, or have Congress and the Patent Office take steps, almost certain to prevent the innovation they claim to treasure.