If you watched the news or picked up a newspaper yesterday you’ll already be aware that scientists in Japan have created genetically modified (GM) marmoset monkeys that pass the transgene, in this case one that encodes the marker GFP protein that glows under UV light, to their offspring. Severel media outlest including the Huffington Post , ABC news, and Washington Post report this advance in… err… glowing terms, while in the Times today the British columnist Hugo Rifkind contrasts the scientists with animal rights activists who are “…prepared to sacrifice other people for monkeys“. On this Hugo has a good point, arguments frequently rage over the question of animal rights supporters using medicines developed through animal research, but the real issue is not whether or not they use these medicines themselves but that they seek to deny them to others who do not share their views.
It’s worth stressing that these are not the first GM monkeys, in 2001 scientists lead by Dr. Anthony Chan at the Oregon Regional Primate Research Centre produced the world’s first transgenic monkey, a rhesus macaque named ANDi, and last year produced the first monkey model of Huntington’s disease but none of these GM macaques have transferred the transgene to their offspring, possibly because it is not present in tissues such as the sperm and egg.
The group lead by Dr. Erika Sasaki (1) used a different technique to previous groups that have created transgenic monkeys, rather than introducing the transgene into unfertilized eggs and then fertilizing them by IVF they found that it was more efficient to take eggs that had already been fertilized naturally and then introduce the transgene, and they carefully adjusted the conditions of the transfer so that the maximum number of copies of the transgene reached the cells of the embryo. They chose the marmoset rather than the macaque for this study because it has a shorter life cycle than the macaque, which means that GM offspring can be generated much more quickly than with macaques, an advantage that means that it should be possible to establish colonies of GM marmosets for research far more quickly than would be the case for macaques. Dr. Sasaki and her colleagues expect that GM marmosets will become a valuable model for diseases where GM rodents are not able to provide all the information scientists require, including some aspects of amyotrophic lateral sclerosis and Huntington’s disease.
Against that macaques are closer to humans in evolutionary terms, so that some human diseases such as tuberculosis can be studied in macaques but not in marmosets, and the smaller brain size and lower cognitive ability of marmosets compared to macaques means that GM macaques will probably complement rather than replace macaques in neuroscience research. It is also probable that some of the techniques developed by Dr. Sasaki and her team can be used to improve the efficiency of GM macaque production, so this should be seen as a boost to GM monkey research in general.
So do these monkeys herald a “health revolution” as the Independent suggests? Well, perhaps evolution would be a more accurate term. Impressive as this achievement is more work will need to be done to improve it, especially to make sure that the correct number of transgenes are safely and efficiently delivered to the tissues where their expression is required. It is certainly worth remembering that while GM monkeys may become an important resource in tomorrow’s medical research they will only ever account for a tiny fraction of GM animals, as they will be used only when scientists are unable to learn enough from GM rodents.
Interestingly Nature has accompanied this paper with an editorial entitled “Time to connect” (2) urging Japanese researchers to make greater efforts to discuss their work with the public in order to prevent the kind of animal rights extremism that we have seen in the US recently or the imposition of regulations that stifle research, as has already happened with human embryonic stem cell research in Japan. While we agree that “Animal research in Japan and its supporters should heed the lessons from the West, where researchers have won several political victories by addressing the issues openly.” we are also keenly aware that scientists and the many charities, companies and government bodies that fund animal research in the US still need to do a lot more to communicate the value and necessity of their work to the general public. We also urge them to show support not just for science but also for those scientists who are targeted by animal rights extremists, and a great way to start would be by signing the Pro-Test Petition.
Regards
Paul Browne
1) Sasaki E. et al. “Generation of transgenic non-human primates with germline transmission” Nature Volume 459, Issue 7246, Pages 523-528 (2009) doi:10.1038/nature08090
2) “Time to connect” Nature Volume 459, Issue 7246, Page 483 (2009)
Speaking of Research 
The availability of GM marmosets will certainly add our understanding of genetic influences on brain function and disease in a dramatic manner. Studies of the relationship between brain and behavior are an area where monkeys play a unique and irreplaceable role; this fact is part of the rationale that leads to their use in my own research program and that of other investigators like myself who seek to develop clues to the origins of clinical brain disorders like schizophrenia, addictions and mood disorders in order to inform treatment development.
There is no debate that these clinical brain disorders are highly heritable, with risk for them depending upon genetic variation that is present in humans and animals alike. To date, the potential significance of variation in single candidate genes has largely been assessed using rodent (mouse) models that carry a transgene or null mutant version of the gene of interest. But, as stated above, the ability to connect the function of that gene to complex brain functions is limited in the mouse. What’s more, what one ends up studying is in the influence of a particular gene on a genetic background somewhat unlike our own; therefore, the ability to detect genetic modification (epistasis: where variation in another gene influences the phenotypic variation associated with the manipulated gene) is made more difficult.
For all these reasons, studying the influences of variation in one gene on a phenotype in monkeys is critical. One, they share many of the complex brain functions we have, and two, the gene effect is studied on a genetic background more like our own.
This makes the developments reported by Sasaki and colleagues very significant.
Ultimately, marmosets are new world primates sharing less genetic relation to humans than, say, macaques or vervets, meaning that transgenic old world monkeys will ultimately be more directly informative. When it comes to the brain, new world monkeys, including marmosets are lissencephalic (smooth brained) but GM marmosets represent a critical “next step” in the progression of GM animal models to research oriented at understanding critical human mental disorders.