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Idea
Dragan Otasevic Oct 05, 2020
Fully autonomous place-and-forget mouse lab
Image credit: Aaron Logan
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A fully automated mouse lab for longitudinal studies. It would be place-and-forget, remotely monitored and operate independently for the full lifespan duration of the mice. The system would manage all the needs such as feeding, cleaning, providing therapy as required by the research.
Such a labs could be placed in enviroments that are dificult to manage (ocean floor, low-radiation deep mines, space, moon, Mars)
Disclaimer: I hate myself for comming up with this idea as well. However, not having such a solution would still result in the same fate for mice, except there would be manual human work involved which would stretch over longer time to achieve the same amount of experiments.
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Creative contributions
Automatic genetical engineering of novel human-disease mouse models
The idea
The research models are good if they can simulate human disease. Nowadays, many diseases are not researched properly due to the lack of proper model organisms. What if we added an abstract feature to the autonomous lab to autonomously generate new mouse models?
Disclaimer:
Personally, I am not okay with an autonomous robot-orchestrated lab that not only feeds mice and cleans their feces but also creates new genetically modified mice that can serve as a research tool. It would further support the development of animal research models since no human would feel guilty of modifying, killing, or "torturing" the animals. I am keen on finding better 2D cell culture or in silico models that can give the same results.
Why?
- Automated genetical engineering could result in thousands of new models
- New mouse models could be tested in the existing databases and compound banks (pharmaceutical companies fishing for compounds)
- Novel gene functions, pathways and connections could contribute to our understanding of the diseases and disorders
- Automated genetical engineering could be made high-throughput
- Easy to combine with sequencing or mass spectrometry to produce new omics data
- Could work as a click&pay center for remote experiments for any scientist in the world
How would it work?
The lab could perform autonomous
- Random transgene insertion
- to discover novel functions of genes, their involvement in signaling and disease development
- any gene at any place
- robot would randomly produce high number of mice with random insertions and scan them through databases for the interesting ones; then it would reshape the transgene or modify the method and try again
- Targeted gene insertion
- to tackle specific problems and explore gene functions within the narrow spectre
- specific gene/s on desired place
- robot would get specific orders to follow in order to find a matching phenotype/genotype that could be used by the customer
Additional information
In past, humanization of mice models was done either by random insertion of transgenes or by targeted genomic humanization. While the first one is cheaper and faster, it was sort of "out of control". Transgenes could be inserted in multiple locations and copies, they could easily split to a single allele through breeding and could disrupt genes near the transgene. The second approach reduced the uncertainty by insertion of a single copy of transgene on a desired location, but at much greater cost and time. Although much more specific and reliable reliable, the targeted genomic humanization still lacks to include pre-mRNA splicing regulation that may have occurredin humans, since cDNA is introduced. To eliminate all the above-mentioned problems, the best thing would be to use new methods such as TruHumanization, which completely replaces mouse gene by human genomic sequence, including the non-coding part.
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General comments
Martina Pesce4 years ago
I believe the idea is brilliant!
Of course, the sooner we manage to research without animals, the better. Unluckily, I really can't imagine animal-free research to start in less than a couple of decades.
A couple of extra reasons why I think is a great idea: 1) researcher security: visible animal facilities attract animal activist which, despite they rightly remind us to move on in finding alternatives methods, can be at times damaging for investigators privacy, security and mental health; 2)researcher mental health: it has been shown that animal experimentation practices stress out researchers [1]-[4].
A couple of elements to keep in mind for the implementation of this idea: 1) if you were serious about extra-earth location, it would be worth to a) recalculate the cost-benefit of producing such faculties (any technical expert who has an opinion on this?) and b) considering that animals are living beings, you do want someone close by to intervene in case of technical malfunctioning; 2) as Shubhankar Kulkarni also mentioned, human handling is a great resource, for example, to avoid the animal loneliness and consequent stress in periods when the animal must be alone (post surgeries periods, implants installation), so maybe some warm human smelling puppet could trick them (or not).
[1] M. R. LaFollette, M. C. Riley, S. Cloutier, C. M. Brady, M. E. O’Haire, and B. N. Gaskill, “Laboratory Animal Welfare Meets Human Welfare: A Cross-Sectional Study of Professional Quality of Life, Including Compassion Fatigue in Laboratory Animal Personnel,” Front. Vet. Sci., 2020.
[2] P. Bennett and V. Rohlf, “Perpetration-induced Traumatic Stress in Persons Who Euthanize Nonhuman Animals in Surgeries , Animal Shelters , and Laboratories,” Soc. Anim., 2005.
[3] R. L. Scotney, D. McLaughlin, and H. L. Keates, “A systematic review of the effects of euthanasia and occupational stress in personnel working with animals in animal shelters, veterinary clinics, and biomedical research facilities,” J. Am. Vet. Med. Assoc., 2015.
[4] M. Kang, A. R. Han, D. E. Kim, T. Seidle, K. M. Lim, and S. J. Bae, “Mental stress from animal experiments: A survey with Korean researchers,” Toxicol. Res., 2018.
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Shubhankar Kulkarni4 years ago
Animals need to be handled with proper care before they are experimented upon. Even rats, when touched or handled abruptly get afraid and that may even lead to a cardiac arrest. While performing experiments on animals, the researchers spend a few days to weeks (before the experiment) to form an acquaintance with the animals. The animals recognize human individuals, mostly via smell. It has been noticed that handling and caressing the animals for a period reduces their anxiety of human touch. Why this is also necessary is because anxiety may also affect the results of your experiment. In the case of an unmanned lab, this anxiety may interfere with your results.
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jnikola4 years ago
I think the idea is great! Why? 1) The research and development would speed-up drastically, which could be especially useful in pandemic bursts like the COVID-19 one. 2) Clinical trials could become a regular thing in experiments (and not the unfathomable dream), by reducing the costs (specialized automated facilities, no personnel, self-sustaining). Also, 3) by eliminating the human mistake and handling factor, experiments could become more reproducible and more credible. 4) Although people are really creative lately (in silico systems, chips, organoids, organs), there is still no system that can worthly replace mice in clinical trials, especially for complex diseases that affect the whole body. -- I agree that organs on chips or in silico methods seem cool and more humane, but there is still a lot to improve until they become reliable testing systems with all the hormones, physical and chemical imprints of the membranes, channels, tubes, pressures and other that gather the whole inter- and intra- cell/organ/tissue dynamics. For at least a decade, other technologies will not be fully accepted, and that´s why these automated mice facilities could remain important (necessary) and continue to make a change in human health research.
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Anja M4 years ago
There is always that question on whether sometimes a full live natural organism is needed to test something, especially if it's so unknown as the surface of some celestial body. However, I remembered two reasons why this may be relieved:
1) Apart from the cruelty part, animal studies are questioned more and more, since their validity in terms of human health and other human-oriented studies often proves not to be enough for more certain conclusions, so this may be an additional reason to put them aside.
2) Organs on chips - This is a news from 2013. where this biologist shows a prototype of a chip where you can plant cells of any organ and then use it for various testing.
https://www.ted.com/talks/geraldine_hamilton_body_parts_on_a_chip#t-787435
Not to mention how this mass-produced makes clinical trials easier, but it can also be custom-made for any individual, and moreover, whole populations and adapted for various testing. I am not sure how it progressed, but I believe it can also succumb to full automation like you suggested. Of course, with proper tuning for a particular need. So maybe something like this can both replace animals and provide some valid tests. If it proves not to be possible, it will probably fail in the same way the validity of animal experiments does to various extents, like I mentioned in 1). Otherwise it can prove beneficial very much, although ultimately, like in the last phase of clinical trials, when the drug is tested on healthy human individuals, we will send someone to remote planets either way. :)
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Povilas S4 years ago
I believe it's possible to come up with solutions not involving cruel animal experiments at all, and this should be the main focus. They exist because humans generally tolerate this - human health and scientific developments are considered to be more important and animal suffering a small price to pay. That's a reflection of speciesism and humans singling themselves out of all the rest of nature, a reflection of collective humanity's ego. I think it's better to do experiments with humans who voluntarily agree on them rather than animals who can't give you an answer because this is like doing experiments on babies who can't talk and understand mental concepts yet - they can't give you an answer, but they will surely suffer.