Animal patents, huh? Humanized transgenic mouse model

Copyright © Françoise Herrrmann -        You, my friend, are crossing the boundaries of your field…No one is going to believe you….! -        Ok, no one is obligated to believe me… But, when you do find someone that you believe, then everything will sound familiar; and you, dear friend, will remember what I’m telling you….! Hush now… and back to transgenic mice, those rodents with knocked out (KO) or knocked in (KI) genes that are perceived as the greatest and most promising avenue of research, for testing drug targets, in-vivo. Here are a few more of these patented creatures –three genotypes just don’t seem to build a big enough case for the existence of a transgenic rodent market and breeding industry.Besides, according to WHO, there are 6000 known rare diseases (with a prevalence of less than 200,000) and more than 12,000 diseases known to plague humans, which means plenty of drug targets to test for generations to come. And incidentally, these batches of mice are “humanized”… so sorry, if your heart is sinking anew… this is another interesting aspect of this type of breeding…  In patent application US2013291134 titled: Humanized transgenic mouse model, the mice are used to test vaccines in vivo. The argument mentioned in favor of humanized mice is that this kind of testing is far too dangerous to perform on humans. I am assuming this means no one would ever give an infectious disease to a human in order to test out a vaccine, which sounds reasonable enough. The point, however, is that no one seems to object to creating animal models of the disease instead. To the contrary, this is state of the art, path-breaking and heralded breakthrough science. In patent application US2013291135 titled: Transgenic model of ALZHEIMER'S DISEASE (AD), “the mice overproduce the amyloid-beta peptide (Abeta) and are deficient in CD45 (PSAPP/CD45-/-), which recapitulates AD neuropathology. The research points to a drug target that validates CD45-mediated microglial clearance of oligomeric Abeta”. Succinctly, this means a cure for AD, considering a mouse model of AD can be created, and the production mechanism can be targeted with a new drug. But this model also assumes that AD may be reduced to the overproduction of a peptide. And I am curious, how it is at all possible to tell that the mice have AD, since mice do little more than squeak, with no pun intended on “p”s and “q”s. But then again, I am not a neurologist…. I am just very worried that mice do not speak ….even if their biology can be engineered to overproduce the required Abeta peptide.  In patent application US2013288361 titled: Neurodegenerative diseases and methods of modeling,“the stem cells and motor neurons derived from mice engineered to carry transgenic alleles of the normal or mutant human SOD1 gene” are disclosed and “the SOD1 transgenic motor neurons are used for the study of neural degenerative diseases”. So, that’s mouse stem cells from mice with a knocked in (KI) human gene, a transgenic process with an additional step. Why not? Advertisements for the production of custom transgenic animals run:  “You think it up, we knock it in or out…”. This is a very creative field, and neurogenerative diseases plague humans in particularly insidious and fatal ways. What better justification could there be? --------------------- I am troubled with the justifications, the inevitability, and the absence of any better alternatives. Who would stop the march of science, and progress? No one. But I would like to build an analogy (with all of its blind spots) drawing on the work the French Nobel laureate Le Clézio, and in particular his work on the Aztec civilization (Le Clézio, 1988).  Le Clézio embarked on an in-depth and marvelous analysis of the Aztecs, including their ritual sacrifices. Although he found no good answer to the question of why the Aztecs felt so compelled to rip out the palpitating hearts of their fellow citizens to feed the hungry gods, he asked another admiring question. What would the world be like had the Aztecs never been exterminated?  Indeed, one might wonder whether the Aztec practices of ritual sacrifice would have survived? How the inevitability and justifications of ritual sacrifice might have evolved ? Whatever the compulsion, how might that have played out? These are obviously speculative questions…. But it makes me wonder whether in the next couple millennia we might not ask a similar question about breeding diseased or suffering animal models. I would dare to hope that either we have found all the cures to our plagues, or we have found ways of modeling (or printing) that no longer invoke sentient creatures and the justified and inevitable fabrication of suffering, even if it is just rodents. Who would stop the march of science and progress? Not I… and certainly not in this scenario…! References Le Clézio, 1988.Le rêve mexicain.France: Gallimard. US2013291134 Humanized transgenic mouse model US2013291135 Transgenic model of ALZHEIMER'S DISEASE US2013288361 Neurodegenerative diseases and methods of modeling Aztec calendar graphic - Carey Joliff Graphic Arts  http://careyjolliffe.wordpress.com/

Animal Patents, huh? Knocked-in (KI) mice

 Copyright © Françoise Herrmann

Readers beware! This post is still rough sailing for your heart.

No kidding…Now that you know all about knockout mice, can you guess what a knockin mouse might be? Here’s a refresher: a knockout mouse is a transgenic mouse, that is, a genetically modified mouse, and in particular a mouse where the function of a specific gene has been altered. So for example, there are insulin-receptor knockout mice useful for studying diabetes and treatment for diabetes.

So… a knockin mouse is a mouse that… is also genetically engineered, but in contrast to a knockout one, the knockin mouse has a gene targeted for insertion in a specific place in its phenotype. And in particular, the mouse may have a knocked in human gene to humanize it for the study of disease and  in vivo testing of particular treatments (Genoway). How’a that for stormy weather?

The EPO returned one patent for humanized “knockin mice”. I am including the abstract just in case this type of engineering pushes you over the edge of belief:

1. WO2012148538 - ANTI-ENDOGLIN ANTIBODIES AND KNOCKIN MICE EXPRESSING NOVEL HUMAN/MOUSE CHIMERIC ENDOGLIN

Provided are compositions and methods that relate to prophylaxis and therapy of angiogenesis associated disease and includes novel knockin mice which express novel human/mouse chimeric endoglin, vectors for use in making such mice, and murine embryonic stem cells comprising the novel human/mouse transgene. Also provided are anti-human endoglin monoclonal antibodies (mAbs) which can be used as antiangiogenic agents for prophylaxis or therapy of human tumor angiogenesis and human angiogenesis-associated diseases having excessive vascularization. The mAbs do not cross react with murine endoglin. Also provides are methods for using the anti -human endoglin mAbs for prophylaxis or therapy of human tumor angiogenesis and for angiogenesis-associated diseases having excessive vascularization.

 For my part, I am not sure that I can "write on.." about these mice. There is such an incredible naivety in drawing a line through the middle of the mammal kingdom that every possible argument on fine lines becomes almost defused. This is cutting-edge research, blinded in a justification of progress and inevitability in the absence of comparable or better alternatives. Who would stop the progress of medicine? 

When I lapse out of consciousness, I wish... I hope.... that Gutenberg will save the day a second time in history, and that soon, we will print human tissues for pharmaceutical testing, complete with a pre-configured genetic makeup, or that computer-generated modeling will do extreme modeling.  I wish ... I hope that philosophers and ethicists might reformulate a quality of life that might include some form of acceptable conclusion, and that our bonds might cease to rip us apart.

And then I regain consciousness, google "knockout", and here is the promise that is returned:

“You think it up, we knock it out…” (InGenious Targeting Laboratory)

Animal patents, huh?

Copyright © Françoise Herrmann Reader beware! The following post concerning patented animals is hardly for the faint of heart.  In 1980, in the case pitting Diamond vs. Chakrabarty, the US Supreme Court ruled, in a landmark decision, that man-made micro-organisms were patentable. By creating a distinction between what is manufactured in the laboratory - "the product of man",  and what nature creates -  which is not patentable pursuant to US patent law (Title 35 of the Federal Code), this decision in fact paved the way for patenting of genetically modified animals. Although the 1980 Supreme Court decision referred to micro-organisms called Pseudomonas which had been genetically engineered with segments of bacterial DNA to “degrade crude oil so as to provide bio-remediation of oil spills”, the highly controversial  psuedo-distinction between “man-made” and “nature-made” created precedence to justify patentability.  Indeed, together with the discovery of DNA in 1953, and subsequent mapping of the human genome, this Supreme Court decision opened the flood gates for patenting  “anything under the sun that is made by man” according to Thickstun (2007), and in particular the patenting of mammals in the laboratory, such as mice, cows, sheep, fish and many others.   As Vandana Shiva has written in her vibrant critique and in-depth analysis of this controversial decision and its consequences: “Currently, well over 190 genetically engineered animals, including fish, cows, mice and pigs are figuratively speaking standing in line to be patented by a variety of researchers and corporations” (Shiva, 1997, p. 20) Patented animals? You are probably worried… or dismissing all of this as scifi. Well, the truth of the matter is that this is far from fiction. So hang in there… The first animal patent, US4736866, was granted to Harvard University researchers as early as 1988, for “Transgenic non-human mice”, trademarked as the Oncomouse™, which is summarized as:   “A transgenic non-human eukaryotic animal whose germ cells and somatic cells contain an activated oncogene sequence introduced into the animal, or an ancestor of the animal, at an embryonic stage.” [Abstract US4736866] With oncogenes inserted into its genome, the Oncomouse™ will now develop cancer, so that the effects of anti-cancer drugs may be tested. In an effort to field some of the more proximate and salient bioethical issues, the researchers do specify that this is a non-human genetically modified animal. And the EPO will also grant the Oncomouse™ patent, 16 years later, on the grounds that the Oncomouse™ is a species that does not exist in nature, and is therefore not subject to the provisions of Article 53(a & b) of the European Patent Convention which (a) excludes patents for inventions “the publication or exploitation of which would be contrary to ordre public or morality” and  (b) excludes patents on “animal varieties or essentially biological processes for the production of… animals.” (Wipo Magazine, June 3/2006)    Apparently slightly distal to the presumably, non-patentable, genetically-modified human, there are issues of furry animal rights, and the suffering caused to these genetically modified creatures and their offspring. But evidently, none critical enough to jar US and European institutions against granting this patent. If you are still here reading this post, then take a peek at the copyrighted picture of an Oncomouse™ from Harvard Medical School.  And, hang in there again… as  there is much more that is genetically modified and patented…      References Siva, V. (1997) Biopiracy: The plunder of nature and knowledge. Boston, MA: South End Press. Thickstun, P. (2007) Intellectual Property and Biotechnology Patents. In the ATA Patent Translators Handbook, pp. 85-96. Alexandria, VA: American Translators Association Wipo Magazine (March, 2006) Bioethics and Patent Law: the case of the oncomouse. .http://www.wipo.int/wipo_magazine/en/2006/03/