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Owning Potential Potential

There is some uncertainty over the relative potency of induced pluripotent stem cells (iPS cells) and human embryonic stem cells (hES cells). Can they become all the cells in the human body as well as organize the embryonic environment including the placenta (in which case they would be “totipotent”), many or all of the body’s cells but not the embryonic environment (in which case they would be “pluripotent”), or only some of the human body’s cells (“multipotent”)? The answer could prove highly relevant to the debate about patenting these cells. If iPS cells or hES cells prove to be totipotent, then one of patent law’s most basic principles – that the legal monopoly conferred by a patent extends only as far as its claims – could work to open up research in the field. But even if the potency of hES cells or iPS cells remains unclear, it still brings us closer than ever to an issue much more familiar to bioethics than the distributional consequences of patent rights, namely, ownership of human life.

A little background is necessary.

For some time now, many have complained that the Wisconsin Alumni Research Foundation (WARF), which controls patent rights in respect of James Thomson’s work with hES cells, threatens to stymie progress in stem cell science – or perhaps already has. In the wake of President Bush’s 2001 decision to bar federal funding for research to create or use new hES cell lines and California’s subsequent vote allocating three billion dollars to stem cell research over ten years, grumblings over the broad scope of WARF’s hES cell patent rights, and how it chose to license them, eventually culminated in a re-examination procedure before the U.S. Patent and Trademark Office. But while these misgivings drove the push by a California-based taxpayers group for re-examination, the USPTO can assess only patentability, not whether a patent is being responsibly licensed. Initially, the USPTO issued a preliminary rejection of three patents held by WARF. But in late February and early March 2008, the USPTO withdrew its previous rejection and affirmed the claims of the patents, in effect bolstering the legal validity of WARF’s rights.

James Thomson was also the senior researcher in one of the two labs that reported generating iPS cells in November 2007. We do not yet know whether WARF filed a patent application in respect of this achievement (applications remain sealed to the public for a period of eighteen months) or intends instead to argue that its hES cell patents encompass iPS cells because they share the same defining criteria, including pluripotency. However, we do know that the other lab that reported developing iPS cells led by Shinya Yamanaka (formerly of Kyoto University), has filed an international patent application claiming “a means for inducing the reprogramming of a differentiated cell without using any embryo or ES cell and establish[ing] an inducible pluripotent stem cell having similar pluripotency.” And the potential for conflict between these (pending) patent rights led Katja Vrtovec and Christopher Scott of Stanford University to hypothesize in Nature Biotechnology that how pluripotence comes to be defined, and whether or not pluripotence is linked to the source from which the stem cells were derived or simply reflects the capacity of the cells no matter their origin, may represent the “next battle” for stem cell intellectual property dominance.

But what about the far end of the cell potency spectrum? What if the very name “induced pluripotent stem cells” assumes that which is actually still up for debate? What if iPS cells as well as hESCs are, in the end, more accurately characterized as totipotent? Recent commentaries inBioethics Forum have touched upon this possibility, and presently there does not appear to be a definitive scientific answer. Cynthia Cohen and Bruce Brandhorst are correct that the totipotency of hESCs or iPS cells has yet to be published. But Gregory Kaebnick andLee Silver are also right that the available data does not close the door on the possibility. If it is eventually shown that hESCs and/or iPS cells are totipotent rather than merely pluripotent, could WARF or Yamanaka (assuming one set of rights prevails over the other or that they do not in fact conflict) be said to own human life?

Here’s the twist: The technical patent law answer to that question is “probably not.” The various patents only explicitly claim pluripotent cells and the legal monopoly conferred by a patent extends only as far as its claims. But if the functional properties of hES cells or iPS cells remain at the margins of toti- and pluripotency, courts and/or real world actors might interpret the claims of the WARF and/or Yamanaka patents as if they encompassed totipotent cells. Of course, the latter scenario assumes that patenting totipotent cells is permissible in the first place, which may not be the case.

In Europe, the bar against patenting the human embryo contained in the European Patent Convention has been interpreted in different ways in relation to stem cells. In the United Kingdom, the Intellectual Property Office has given formal notice that totipotent stem cells are not patentable whereas pluripotent or multipotent ones in principle are assuming all other patentability requirements are met. Canadian authorities recently proposed to adopt the same rule of practice. The European Patent Office at least as of 2006, has not issued a single patent involvling a direct claim to hES cells – whether described as multi-, pluri-, or totipotent. (Gerard Porter and colleagues discussed this issue recently in Nature Biotechnology) In the absence of an analogous provision in the United States and a general hostility to addressing perceived issues of morality through the patent system, the situation is far less clear. In the past, the USPTO has cited the Thirteenth Amendment, which prohibits slavery, in order to preclude patents on inventions comprising humans, including, most famously, the Newman-Rifkin “humanzee patent” in 2004. This same rationale could be invoked to preclude patents on totipotent stem cells, but the USPTO’s authority to do so is extremely tenuous in light of U.S. Supreme Court jurisprudence.

Stepping back from the minutia of patent law, what are we to think of all this?

If what we care most about is advancing stem cell research as a whole, drawing a bright line between totipotent and pluri-/multipotent cells – even if scientifically dubious – might seem like a good move if we believe WARF’s behavior has been damaging. Once characterized as totipotent, researchers would in principle be entitled to use hES cells and/or iPS cells without fear of liability for patent infringement. Unfortunately, however, that assumes that stem cell researchers have already secured access to or can generate such cells on their own, which often is not true. The fact that federal funds cannot presently be used to create new cell lines is also a significant limiting factor in most of the United States.

In the more likely event that ambiguity between totipotency and pluripotency persists, patents on hES or iPS cells become deeply troubling from a moral point of view. Technically, patents do not signal ownership of a thing per se, but rather ownership of a bundle of exclusive rights to make, use, and sell the thing. And technically, WARF or Yamanaka’s patent claims may not extend to totipotent stem cells (in jurisdictions where such claims are legitimate). However, in the real lived world, patent-holders will have de facto ownership/control over the same. They will, in other words, possess the exclusive right to make, use, and sell stem cells that potentially have the potential to become human beings. Maybe they never will; maybe the various regulations that are in place will work to preclude that from happening. But there can be no question that this takes us closer to the issue of owning life – closer, for example, than the genetically modified bacterium in Diamond v. Chakrabarty, than Harvard’s “oncomouse,” and even than the Newman-Rifkin humanzee.

Seen in this light, the advent of research with iPS cells would no longer represent a way of circumventing moral objections to hES cell research. Instead, it would substitute one moral concern (destroying human life) with another (commodifying human life). Depending on one’s views about the moral status of the human embryo, research with hES cells could impinge upon both. No matter where you stand, however, sorting though this issue promises to be very hard, and that’s without even grappling with the distribution of burdens (especially upon women) and benefits likely to flow from stem cell science to living people.

Matthew Herder is visiting professor of law at Loyola University Chicago.

Published on: May 6, 2008
Published in: Bioethics, Emerging Biotechnology

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