Michael Crichton's Nightmare: Not Just Talking Monkeys, But Patentable Talking Monkeys

    By Kevin E. Noonan --

The significance of single nucleotide polymorphisms (SNPs) has been appreciated in genetic research ever since the discovery in the early 1980's that SNPs could produce genetic markers known as restriction fragment length polymorphisms (RFLPs).  However, although this type of polymorphism is responsible for well-recognized genetic mutations (for example, in sickle cell anemia, where an A to T transversion mutation changes a glutamic acid to a valine at position six of the amino acid sequence of the  hemoglobin beta-chain), the significance of this type of genetic mutation has been appreciated more than it has been observed - but when observed, such mutations have occasionally been significant (see, for example, U.S. Patent No. 6,051,379).

A striking example of a SNP that alters gene expression and gene product function has been found in a human gene encoding kallikrein-8 (KLK-8).  KLK-8 is a gene expressed in brain and known to be involved in speech and memory.  It was also known that humans differed from mice in producing a splice variant containing an additional 45 amino acids encoded in the intervening sequence adjoining the third exon (which sequence is spliced out in mice but retained in the mRNA produced in human brain tissue).  The significance of this change has been unappreciated, at least in part due to the phylogenetic distance between mice and man.  The analysis of these differences in species closer to man evolutionarily, specifically chimpanzees and other great apes, sheds new light on its significance.

As reported on May 8, 2007 in the online version of Human Mutation, scientists from the Chinese Academy of Sciences have identified a transversion mutation in human KLK-8 gene.  As a consequence, human KLK-8 is alternatively-spliced in human brain tissue, with one of the resulting transcripts being identical to the mouse transcript, and the other having an additional 45 amino acids encoded by exon 3.  In their analysis, these researchers showed not only that the "long form" variant was not expressed in other primates (or any other mammalian species studied), but that the capacity for producing this alternatively-spliced transcript was due to an T to A mutation in the intervening sequence between coding exons 2 and 3.  Other primates do not have this mutation, only humans do (and there is no polymorphism detected among different human racial groups, suggesting this mutation is "fixed" in the human genome), and it can be traced to an event that occurred about 5 million years ago.  The mutation creates a "splicing enhancer" sequence that creates the long form transcript for the first time in primate evolution.

It has been evident for some time that the small overall differences between human and chimpanzee genomic DNA (on the order of 1-2%) could explain the phenotypic differences between the species based not on how many genetic sequence differences there are but on which sequences are different.  The possibilities for genetic differences that are responsible for the species differences include those operating at a histological level (such as chromosomal rearrangements, both local and global, and genetic duplication) and on the genetic level (such as SNPs, alternative splicing, and differential gene expression).  Significantly, human neural tissue exhibits a high level of alternative splicing events, one of the proposed mechanisms that reconcile the phenotypic differences between humans and other primates and the relatively small human transcriptome size (30,000-45,000 genes rather than the anticipated ~100,000 human genes).

The discovery of the KLK-8 mutation, and the existence of transgenic animal technology, suggests the possibility that a transgenic chimpanzee can be produced that expresses the long form of KLK-8 in neural tissues.  Indeed, the only sure way to determine whether this mutation had any effect on neural function would be to make such a transgenic animal.  And this is where it gets interesting (or terrifying, depending on your point of view).  KLK-8 is believed to be involved in the physiological mediation of speech in the brain, and the coincidence of the unique abilities of humans for speech and the existence of the long form mutation raises the possibility that any such transgenic chimpanzee would have an enhanced ability to learn to speak.  Classic attempts to teach other primates to speak (notably, "Nim Chimpsky," at left, in the 1970's) demonstrated that these animals have whatever brain structures or functions are required to be capable of making connections between human words and objects (even emotions).  Thus, a transgenic chimpanzee might be able to speak, and if so, verbal communication with another species could occur for the first time.

The possibilities for bridging the gap in our understanding of how another species thinks are tantalizing.  Other possibilities are less felicitous, including the realization that such a talking chimpanzee is eminently patentable.  U.S. law has a strict prohibition on patenting humans - the 13th Amendment banning slavery - and attempts by Jeremy Rifkin and others to patent human/animal chimeras have been thwarted by administrative decisions in the U.S. Patent and Trademark Office.  (In this regard, the British Department of Health recently reversed a ban on such chimeras, although it has not yet passed the House of Commons.)  There are no such prohibitions against transgenic primate patenting (transgenic animal patent claims usually recite a "non-human" animal), and given the costs of producing such a transgenic chimp, patent protection may be necessary to garner sufficient investment.

Whether the results of these studies will resemble "Dr. Doolittle" or "Planet of the Apes" is, of course, impossible to predict.  However, it is likely that anyone (like author Michael Crichton) who is unconvinced about the wisdom of permitting "patenting life" will be politically opposed, and the extent to which such opposition is persuasive will determine the fate of any attempts to own a talking monkey.

Dr. Noonan has written a number of related articles for Patent Docs, including:

• "The Future of DNA Patenting," February 20, 2007
• "A DNA Patenting Thought Experiment," February 16, 2007
• "Science Fiction in The New York Times," February 13, 2007
• "The Continuing Value of Biotech Patenting," February 4, 2007
• "Anti-Patent (Sullivan?) Malice by the New York Times," January 29, 2007
• "In Support of Gene Patenting," December 7, 2006

Comments

[The Chimperor]

What is the moral difference between the right to own chimps outright (which many institutions and individuals already do and very few people question), and having a patent on a class of chimps which prevents others from owning that class without your permission?

I don't see a big distinction.

As for whether a patent should be allowed on a method of making such a chimp, that begs the question: does "society" want such manipulations to be legal at all?

In any event, if a talking chimp can be made this way, expect someone to try to do it, if they haven't already. Then we can ask "deep" questions like whether a chimp has a soul. I imagine Fox News will have a very thoughtful program devoted to the topic.

[Kevin E, Noonan]

I think the distinction is human sentience, which is typically detected by language. I think most people would say primates, dolphins and some whales have an intelligence related to human intelligence, but since we can't ask we can't be sure - the gap is as wide for a chimp as it is for a cat, which is why chimps and cats can be "owned outright."

My question is what happens when the chimp can talk, and maybe enunciate in a way humans can understand its ideas and feelings. That creates moral issues, and as it relates to patent law such moral issues are behind opponents of stem cells, gene and transgenic animal patenting. So my post simply was intended to provoke a discussion about that.

Thanks for the comment.

[The Chimperor]

Kevin writes

"My question is what happens when the chimp can talk, and maybe enunciate in a way humans can understand its ideas and feelings. That creates moral issues"

I think most of the "moral issues" are already on the table. I recommend watching Fred Wiseman's classic documenary film, "Primate," for a fairly objective view of the relationship between humans and animals. Somewhat more abstractly, the documentaries "Our Daily Bread" and "The Wild Parrots of Telegraph Hill" also touch on the key issues.

Humans and animals are both capable of communicating their "feelings" quite clearly without speaking. In fact, many healthy animals, spectacularly including chimps, are far better at communicating their feelings than mentally ill or traumatized human beings.

Is a verbal conversation with a lab-raised chimpanzee really needed to determine what chimpanzees want or need from humans?

Gosh, I hope not.

[Kevin E. Noonan]

Chimperor:

I don't dispute that animals can communicate with humans - my cats are very good at telling me what to do and getting me to do it!

Having said that, I maintain that there is a qualitative difference between understanding animals as we do now and actually conversing with another species. And I think the issue would be huge, if only because it would be harder to say "S/he's only an animal" and disregard the animal's feelings. I've had vets tell me that "animals don't feel pain like humans" when trying to convince me to declaw my cats (nothing doing!), and laymen espouse even more ignorant views of the considerations merited by brutes and beasts.

Like it (or agree with it) or not, in my view an aggrieved tirade from an insulted chimp would be a qualitatively different experience, and provoke a qualitatively different response.

Thanks for the comment.