I’m interested in your opinions on this.
An important paper just appeared in the prestigious British journal Brain from researchers in Bordeaux, France and Lausanne, Switzerland led by Dr. Morgane Darricau, a junior scientist working with eight other scientists under senior researchers Dr. Erwan Bezard and Dr. Vincent Planche.
The work was performed using rhesus monkeys, also called “macaques,” which have been productively and frequently used in research for over a century. The researchers injected abnormal tau protein from patients with PSP into the midbrain of two macaques. As controls, they injected normal tau from the brains of two people whose autopsies showed no neurological disease into the midbrain of two other macaques. The result was that starting six months later, the first group started to show abnormal control of walking and loss of performance on a cognitive task requiring opening a box containing a treat.
The deficits progressed, and after another 12 months, the animals were euthanized. Brain tissue of the two recipients of the abnormal tau showed the same sort of tau aggregation seen in human PSP. Also, crucially, the tau abnormality had spread to several areas known to be connected to the original injection. Those areas — the putamen, caudate, globus pallidus and thalamus — are among the main sites of involvement in human PSP. They must have received the abnormality from the injection site through axons and across synapses, not by mere proximity. The two control macaques had neither symptoms nor brain abnormalities at autopsy.
Similar experiments have been done with mice over the past decade with similar results, but:
- The mice did not display the full range of PSP-related brain changes that occurred in the monkeys.
- The mouse brain’s simpler circuitry and much smaller size do not closely mimic the “environment” in which the abnormal tau spreads in human PSP.
- The types of normal tau in the brain, a mix of 3R and 4R, is like that of humans, while normal mice produce only the 3R type. (“R” is a stretch of amino acids in the tau protein that allows it to attach to the brain cells’ microtubules. The number is how many such stretches exist in the tau molecule.) This suggests that macaques and humans share a similar genetic control of tau production.
- The complexity of monkeys’ normal movements and cognitive processes more closely resemble those of humans, allowing more valid extension of the experimental observations to humans and their diseases. This complexity also allows a finer-grained evaluation of the effects of the experimental intervention.
The authors point out that while only four macaques were necessary to demonstrate this result, larger numbers would be needed to confirm the findings and to turn this model into a practical research tool. Once that happens, many research labs the world over could use this technique in studying PSP and testing drugs designed to slow, stop or reverse its progression.
Now here’s the issue at hand: The last line of the paper is:
“ . . . our results support the use of PSP-tau inoculated macaques as relevant animal models to accelerate drug development targeting this rare and fatal neurodegenerative disease.”
At one level, they are probably right: using macaques in research would bring a cure for PSP faster than using mice. But some people oppose the use of animals of this level of intelligence in scientific research, no matter the benefit to humans. I’m interested in your opinion: should macaques be used in PSP research?
No, I don’t know how many macaques might ultimately be needed. Nor do I know how much sooner a cure would be found compared to the present practice of using only rodents. So, try to provide an opinion that transcends those important specifications.
Please use the “reply” or “leave a comment” feature (whichever your browser shows) below. Thanks.
3 thoughts on “A step forward or backward? Let’s vote.”
Absolutely. Yes, macaques should be used in PSP research. We need to speed up research to achieve real progress on PSP treatments (and perhaps treatments of other tauopathies). Using macaques for such purposes would greatly outweigh any ethical concerns.
I guess we have some “skin in the game” as recently we received a diagnosis in the family. As a scientist myself, I am excited to read that the macaques may provide a proxy biochemical environment that will probably help accelerate PSP research.
I have not read or thought about the subject at all before now. Why do we think that using macaques is more unethical as compared to rodents? How should we choose? Based on having a more evolved neurological system, yet not evolved enough to give consent?
But this sort of choice based on sentient scale is very anthropomorphic – and maybe we feel the hesitation because macaques are closer to humans than rodents! Ethically, if consent is the driving factor, then rodents should not be used either -especially given the fact that they are not really suitable proxy environments scientifically! In some sense people “care” less about rodents than macaques – and thus it seems that rodents are used because they can be, not based on any conscious choice.
The balance of scientific and ethical concerns seems to lie at the level of the rodent species, currently. To push it towards efficient science alone, one must give more weight to finding out a scientific cure and let go of the notion that we are not harming any other species -and accept that we are trying to save ourselves and in that “hunt” we are utilizing macaques as test environments.
To push it the other way – hypothetically, one may question the use of any other species. Since they have to be “infected” with the abnormal tau proteins – why not use the humans affected with PSP themselves(if they care to consent!)? And if most humans do not care to consent, then no medical trials on animals may be considered “ethical” – if consent and equality of all living beings (with respect to priority in being selected for suffering) are considered the parameters that define the “ethical” choice.
. . .
In short, I am of the opinion that no medical trials can be considered “ethical”. But such balances exist elsewhere as well – meat eating, for instance. So, if we accept that to save ourselves – as a species – we will harm others (eat them!), then using macaques to advance a cure for PSP instead of rodents does make a good case scientifically. Though it makes me wince to write that, it is still not likely to break the implicit trust we have in humanity – just that none of us will be reaching sainthood anytime soon!
Thanks for that thoughtful reply, DK.