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? Ornamental fish

Copyright © Françoise Herrmann

So, let me count the ways we breed in our most sophisticated labs…. We have KO and KI mice. These are mice bred with a gene that is knocked-out or knocked in for the purposes of testing drugs. Remember, the CISD2-KNOCKOUT MICE, the ones bred to exhibit a mitochondrial breakdown and dysfunction, to model the Wolfman Syndrome of premature aging? (Yes, that was the basis of what Brad Pit showed us in The curious case of Benjamin Button, only that was just motion picture.) Remember also the ATRN AND ATRNL1 DOUBLE GENE-KNOCKOUT MICE modeling heart disease, and the NRIPKNOCKOUT MICE modeling muscular dysfunction? Yes, all those mice are circulating around the world for testing new molecules which might reverse, control or attenuate certain diseases that plague humans everywhere.

Well, there’s lots mo’ to this transgenic story. There is plenty of variation and creativity here, both in terms of the diversity of the knockouts or knockins, and the species of animals concerned. The difficulty lies only in how many and how much you can handle at a time…

 Take for instance the ornamental fluorescent fish marketed as GLOFISH®. These are also genetically modified creatures, designed to glow under ultraviolet or blue light in fish tanks. The fish species concerned are Zebrafish (Zebra danio). They have a gene knockedin that encodes various fluoresecent proteins such as the green fluorescent gene protein (GFP) found in jelly fish (Aequorea victoria), the green fluorescent gene protein (GPF) found in sea pansies (Renilla reiformis),  the dsRed fluorescent gene protein found in mushroom coral (Discosoma), the eqFP611 fluorescent gene protein found in sea anemones (Entacmea quadricolor), the RTMS5 fluorescent gene protein found in stony coral (Montipora efflorescens), the Dronpa fluorescent gene protein found in chalice  coral (Pectiniidae), the kindling fluorescent protein (KFP) found in Venus hair anemones (Anemonia sulcata), the eosFP gene found in open brain coral (Lobophyllia hemprichii), and the Dendra fluorescent gene protein found in actocoral (Dendronephthya).  Thus,  depending on the fluorescent gene knockedin, the fish glow in various colors such as green (Electric Green Glofish® ),  red (Starfire Red Glofish®), blue (Cosmic Blue Glofish ®), purple (Galactic Purple Glofish®), etc.

The patent for these fish is titled: CHIMERIC GENE CONSTRUCTS FOR GENERATION OF FLUORESCENT TRANSGENIC ORNAMENTAL FISH [WO0049150].

Below you will find the abstract for this genetically modified (GM) zebrafish patent:

Four zebrafish gene promoters, which are skin specific, muscle specific, skeletal muscle specific and ubiquitously expressed respectively, were isolated and ligated to the 5' end of the EGFP gene. When the resulting chimeric gene constructs were introduced into zebrafish, the transgenic zebrafish emit green fluorescence under a blue light or ultraviolet light according to the specificity of the promoters used. Thus, new varieties of ornamental fish of different fluorescence patterns, e.g., skin fluorescence, muscle fluorescence, skeletal muscle-specific and/or ubiquitous fluorescence, are developed.  [Abstract WO0049150 - Chimeric gene constructs for generation of fluorescent transgenic ornamental fish]

 PS. In 2003, the FDA cleared the sale of Glofish® in the US on the grounds these fish are not used for food purposes, and therefore pose no public health risk. In 2005, the lawsuit filed by The Center for Food Safety to block the sale of Glofish® in the US was found without merit. The Center argued that the sale of Glofish® would set precedence and open the floodgates for nonfood genetically modified animals.

Beyond the ornamental… and for what it’s worth… there are other experimental uses of fluorescence as bio-markers for the detection of pollution and chemicals, only this FISH (Fluorescence In Situ Hybridization)  is hardly sentient… In fact, that’s a whole other patent species… (!)

 References

-        The Center for food Safetyhttp://www.centerforfoodsafety.org/

-          The curious case of Benjamin ButtonThe curious case of Benjamin Button.(2008) directed by David Fincher, starring Brad Pitt and Cate Blanchett.  Based on the novel by Scott Fitzgerald
  

-         - Beskid, O., Binkova, B., Dusek, Z., Rossner, P., Solansky, I. Kalina, I., Zidzik, J., Popov, T.A., Farmer, P.B.  and R.J. Sram (2007) Chromosomal aberrations by fluorescence in situ hybridization (FISH) -- biomarker of exposure to carcinogenic PAHs. Journal of Mutation Research, Jul 1:620(1-2): 62-70. http://www.ncbi.nlm.nih.gov/pubmed/17412370