Demand is skyrocketing in China for mice that mimic the diseases of humans(bloomberg.com)
bloomberg.com
Demand is skyrocketing in China for mice that mimic the diseases of humans
https://www.bloomberg.com/news/articles/2019-04-01/china-s-demand-for-17-000-gene-altered-lab-mice-is-skyrocketing
4 comments
They're bred to be sick and live in a lab, so they and any of their progeny would not be likely to survive very long. They're not zombies, so them biting other animals wouldn't be a huge concern either.
>What would happen if the mice escaped the facility, and bite other animals or humans
Genes don't typically transfer that way. Except for extraordinary circumstances where the disease is caused by some sort of virus, getting bit by someone with hemophilia or cystic fibrosis or down syndrome isn't going to give you the disease.
>or breed with 'normal' mice
It's not impossible for this to happen, but in general these mice have been bred for generations in a lab environment where they are provided with food and water without having to find it on their own. The world is already a harsh place for a normal mouse that is well adapted to it, so if you add in a "soft" mouse with some sort of debilitating genetic disorder, I wouldn't worry too much about it taking over the world.
Genes don't typically transfer that way. Except for extraordinary circumstances where the disease is caused by some sort of virus, getting bit by someone with hemophilia or cystic fibrosis or down syndrome isn't going to give you the disease.
>or breed with 'normal' mice
It's not impossible for this to happen, but in general these mice have been bred for generations in a lab environment where they are provided with food and water without having to find it on their own. The world is already a harsh place for a normal mouse that is well adapted to it, so if you add in a "soft" mouse with some sort of debilitating genetic disorder, I wouldn't worry too much about it taking over the world.
What happens if man made super food like the Broccoli escapes it's man made field? Nothing. It can't compete with plants in the harsh natural competition for the survival of the fittest, because it hasn't been bred for that. It's only been bred to grow and grow, not to a wage war for survival against it's surroundings like all other plants in nature do.
> It can't compete with plants in the harsh natural competition for the survival of the fittest, because it hasn't been bred for that.
not a biologist in any way, but i'm pretty sure an addition/modification of one trait to an existing genetic line doesn't immediately render null-and-void all existing fitness of that line, such that they are immediately so unfit as to not propigate further
not a biologist in any way, but i'm pretty sure an addition/modification of one trait to an existing genetic line doesn't immediately render null-and-void all existing fitness of that line, such that they are immediately so unfit as to not propigate further
>i'm pretty sure an addition/modification of one trait to an existing genetic line doesn't immediately render null-and-void all existing fitness of that line
That's true, but these lab lines generally are inbred for generations on purpose before the disease gene is even added, so even the "normal" lab mice without the disease are quite different than wild mice, and even quite different than other strains of lab mice.
That's true, but these lab lines generally are inbred for generations on purpose before the disease gene is even added, so even the "normal" lab mice without the disease are quite different than wild mice, and even quite different than other strains of lab mice.
There is a very small risk that artificial transgenic DNA sequences can cause "transformation" (horizontal gene transfer) from the genetically modified plant to wild bacteria, with unknown consequences.
The protections are not to protect us from the mice, it’s to protect the mice from us. The value of the mice is in their purity. Imagine basing a 1bn investment in a new drug based on trials that it turned out were tainted because a mouse caught something from a human handler beforehand. Hence 17k a mouse.
These numbers seem amazingly small.
I would expect there to be at least 10 billion lab-mice worldwide - enough for an almost 1:1 pairing with humans. You can't do large population scale studies of disease spread and antibiotic resistance etc. unless you have big populations. We also have tens of thousands of man made chemicals we need to know the safety of, and a simple test on 100 mice isn't going to detect the subtle side effects.
Mice are so easy to keep, they could be entitely mechanicly reared, and an experiment involving 1000 mice should be a simple matter of a few clicks on a computer.
I would expect there to be at least 10 billion lab-mice worldwide - enough for an almost 1:1 pairing with humans. You can't do large population scale studies of disease spread and antibiotic resistance etc. unless you have big populations. We also have tens of thousands of man made chemicals we need to know the safety of, and a simple test on 100 mice isn't going to detect the subtle side effects.
Mice are so easy to keep, they could be entitely mechanicly reared, and an experiment involving 1000 mice should be a simple matter of a few clicks on a computer.
Most animal experiments are performed only if an effect size large enough to be ascertained using a small number of mice (i.e. <10, typically) is predicted based on in vitro or other models. Grant funded researchers do not typically have the resources to maintain such large colonies as you propose.
Also, most mice used in experimentation are inbred strains. Most human studies rely on such huge sample sizes to to identify low effect sizes within a diverse population.
Also, most mice used in experimentation are inbred strains. Most human studies rely on such huge sample sizes to to identify low effect sizes within a diverse population.
>Mice are so easy to keep, they could be entitely mechanicly reared, and an experiment involving 1000 mice should be a simple matter of a few clicks on a computer.
I invite you to go visit a laboratory that works with rodent models for a few days and see if you still think this is true. I would love to be proven wrong, but in my experience animal experiments are as non-automatable as human clinical trials. As a simple example, in my PhD I spent months injecting mice with cancer cells, measuring the tumor outgrowth, then harvesting the tumors, grinding them up and sequencing them. You can see the schematics of some of those experiments in one of my manuscripts (https://elifesciences.org/articles/41090 -- free to access). Each one of those experiments relied on dozens of different techniques (from cloning to making viruses to culturing cells to animal husbandry), most of which are not easy to automate because they vary from experiment to experiment. For instance, just to grow the cells for injection into animals, you need to monitor plates of cells growing in a sealed 37º incubator, wash and re-feed them as necessary over a period of days to weeks. Then, on the day of injection, you need to wash and spin them down, resuspend in an injection solution, put them on ice, go down to the mouse house, shave the mice, anesthetize them and then inject them. You don't want too much time to elapse between when you prep the cells and when you inject them or they might die. At every step there are biosafety constraints that limit your movements and how you dispose of garbage which would be challenging to scale up to a totally automated system. Every different cell line/type you inject has different kind of growth requirements and idiosyncrasies in how they like to be handled. I suppose you could program machines to do this for one cell line, but it would be a monumentally difficult task to do it for every cell line and get good results. Then there's the matter of just handling the animals. I would love to see a machine that could do this (and maybe one day there will be) but for the moment you need training in how to carefully and safely grab mice, restrain them, inject them and so on.
The costs of maintaining mice is also much larger than it seems (perhaps compared to mice kept as pets). A major cost is the daily tasks associated with husbandry, like cleaning cages, sick checks, genotyping, etc. At least at my institute it was ~$1.50 per day per cage (up to 5 mice) in support costs, not including the ~$30-50 it costs to raise a wild-type mouse to the point where you could do the experiment (more for some genetically modified mice). An experiment with 500 mice (100 x 5 conditions) would cost you $15-20k, which would massively balloon the cost of research.
Finally, there are major ethical concerns with using more animals than necessary for any experiment. Animal work is carefully regulated by internal and external ethics committees and oversight of all ongoing experiments. The number of animals to be used for any given project must be justified with statistical analysis suggesting that you are using no more than necessary and will indeed be able to show the expected results. If you propose experiments using large numbers of animals you must have a good explanation for why you need such numbers.
Anyway, it's not really that simple or cheap to do animal experiments, especially at large scale.
I invite you to go visit a laboratory that works with rodent models for a few days and see if you still think this is true. I would love to be proven wrong, but in my experience animal experiments are as non-automatable as human clinical trials. As a simple example, in my PhD I spent months injecting mice with cancer cells, measuring the tumor outgrowth, then harvesting the tumors, grinding them up and sequencing them. You can see the schematics of some of those experiments in one of my manuscripts (https://elifesciences.org/articles/41090 -- free to access). Each one of those experiments relied on dozens of different techniques (from cloning to making viruses to culturing cells to animal husbandry), most of which are not easy to automate because they vary from experiment to experiment. For instance, just to grow the cells for injection into animals, you need to monitor plates of cells growing in a sealed 37º incubator, wash and re-feed them as necessary over a period of days to weeks. Then, on the day of injection, you need to wash and spin them down, resuspend in an injection solution, put them on ice, go down to the mouse house, shave the mice, anesthetize them and then inject them. You don't want too much time to elapse between when you prep the cells and when you inject them or they might die. At every step there are biosafety constraints that limit your movements and how you dispose of garbage which would be challenging to scale up to a totally automated system. Every different cell line/type you inject has different kind of growth requirements and idiosyncrasies in how they like to be handled. I suppose you could program machines to do this for one cell line, but it would be a monumentally difficult task to do it for every cell line and get good results. Then there's the matter of just handling the animals. I would love to see a machine that could do this (and maybe one day there will be) but for the moment you need training in how to carefully and safely grab mice, restrain them, inject them and so on.
The costs of maintaining mice is also much larger than it seems (perhaps compared to mice kept as pets). A major cost is the daily tasks associated with husbandry, like cleaning cages, sick checks, genotyping, etc. At least at my institute it was ~$1.50 per day per cage (up to 5 mice) in support costs, not including the ~$30-50 it costs to raise a wild-type mouse to the point where you could do the experiment (more for some genetically modified mice). An experiment with 500 mice (100 x 5 conditions) would cost you $15-20k, which would massively balloon the cost of research.
Finally, there are major ethical concerns with using more animals than necessary for any experiment. Animal work is carefully regulated by internal and external ethics committees and oversight of all ongoing experiments. The number of animals to be used for any given project must be justified with statistical analysis suggesting that you are using no more than necessary and will indeed be able to show the expected results. If you propose experiments using large numbers of animals you must have a good explanation for why you need such numbers.
Anyway, it's not really that simple or cheap to do animal experiments, especially at large scale.
To add on to this... I was at HHMI Janelia for a while which has an automated rodent cage cleaning contraption with two robot arms. They have all the automation money can buy. It's still __extremely__ labor intensive.
Beyond all the routine things... consider that, at least in neuroscience, you often need to perform surgery on each mouse...
Beyond all the routine things... consider that, at least in neuroscience, you often need to perform surgery on each mouse...
(Sorry for the elementary questions, but this process sounds interesting and I'm curious how it works)
> I spent months injecting mice with cancer cells
How do you inject cancer cells? Is it just a syringe that goes into the blood stream or is it intramuscular? Basically, do you have to find tiny veins on the mice using a small syringe tip?
> you need to wash and spin them down
Are you referring to the animal here or prepping the injection?
Also, I'd imagine it would be hard if you had to paralyze a mouse/rat for research on physical disabilities or other more invasive things than just injecting cancer.
> I spent months injecting mice with cancer cells
How do you inject cancer cells? Is it just a syringe that goes into the blood stream or is it intramuscular? Basically, do you have to find tiny veins on the mice using a small syringe tip?
> you need to wash and spin them down
Are you referring to the animal here or prepping the injection?
Also, I'd imagine it would be hard if you had to paralyze a mouse/rat for research on physical disabilities or other more invasive things than just injecting cancer.
Many things that are done in biology (and medicine to some extent) are way simpler than they seem because much of it was figured out a long time ago using tools that scientists/doctors had at hand.
We grow cells in what is essentially sugar water + some growth factors that we get from cow serum (b/c America has lots of cows). Google tissue culture 101 videos on youtube to get an idea of how it all works. You can't (and don't want) to inject the animals with all that fluid + protein (it can be liters), so you transfer the cells into tubes and spin them in a centrifuge (~300 x g). Spinning them will bring them to the bottom of the tube and they will form a pellet. The pellet sticks to the bottom as you literally dump the fluid out. Now you can resuspend the cells in a few microliters of a saline solution and inject them into the mice.
For example, cells growing in an incubator usually need to be at a density of 200k-1e6/ml so that they have enough nutrients and waste doesn't build up too quickly. For 5e6 cells, that would be 5-25ml of fluid, which is WAY too much to inject into a mouse, so you have to concentrate the cells into a much smaller volume before you can inject. I will typically inject mice with 100µl of fluid containing 5e6 cells.
In terms of injection, you can google subcutaneous injections in mice to see how it's done. It's the same as if you've ever had a tuberculosis skin test or a minor operation where they injected you with lidocaine locally (or what your dentist does). The cancer cells are injected into the space right under the skin.
We grow cells in what is essentially sugar water + some growth factors that we get from cow serum (b/c America has lots of cows). Google tissue culture 101 videos on youtube to get an idea of how it all works. You can't (and don't want) to inject the animals with all that fluid + protein (it can be liters), so you transfer the cells into tubes and spin them in a centrifuge (~300 x g). Spinning them will bring them to the bottom of the tube and they will form a pellet. The pellet sticks to the bottom as you literally dump the fluid out. Now you can resuspend the cells in a few microliters of a saline solution and inject them into the mice.
For example, cells growing in an incubator usually need to be at a density of 200k-1e6/ml so that they have enough nutrients and waste doesn't build up too quickly. For 5e6 cells, that would be 5-25ml of fluid, which is WAY too much to inject into a mouse, so you have to concentrate the cells into a much smaller volume before you can inject. I will typically inject mice with 100µl of fluid containing 5e6 cells.
In terms of injection, you can google subcutaneous injections in mice to see how it's done. It's the same as if you've ever had a tuberculosis skin test or a minor operation where they injected you with lidocaine locally (or what your dentist does). The cancer cells are injected into the space right under the skin.
Right, I should have figured you meant centrifuge when talking about spinning. And interesting re: subcutaneous injections, I watched a video, seems pretty straight forward.
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Mice breed really fast - why does a mouse command a high price like that if you can make a new one for $10 in feed and 3 months?
Transgenes can affect the fertility of mice or mess with their sexual behavior, it's not uncommon for transgenic lines to have erratic breeding schedules and reduced litter sizes compared to wild-type. Then if you get a litter, maternal care is very important. If a transgene messes up the mother's ability/drive to feed the pups, then they aren't going to make it very long (though you can foster/wet nurse them). Finally, depending on the required genetic profile, you may have a situation where only 50% or less of the offspring have the transgene of interest.
Some of this is "worst case scenario" stuff that wont apply to most lines. The real reason for the high price is mostly 1) that its expensive to make the transgenic mice in the first place and 2) demand is high enough that they can get away with charging that much.
Some of this is "worst case scenario" stuff that wont apply to most lines. The real reason for the high price is mostly 1) that its expensive to make the transgenic mice in the first place and 2) demand is high enough that they can get away with charging that much.
I believe the mice used in a lot of research studies need to be genetically identical, so they need to be certain generation crosses
The expenses associated with animal husbandry at most research institutes raise the price to ~$1/day per cage of 5 mice.
So let's examine a setup with three cages, with two parent mice having a litter of 6 every 45 days. So every 45 days we have a new batch of 90-day-old mice, and they cost $135 or $23 each. Add a couple more dollars to sustain the ancestor mice, add enough inefficiencies to double the cost, that's still only $50 per mouse. Rearing costs aren't even going to hit 1% of $17000.
In practice you need to maintain large colonies in order to reliably have enough mice for experiments. Also you need to keep gender in mind because females can be housed together but males cannot and generally experiments are conducted in either one gender or the other.
So, let's say you need 20 female mice for an experiment (e.g. 4 groups of 5). That means that you need to have >40 offspring in order to get enough female offspring. That's at least 7 breeding pairs (assuming you're not harem breeding) and you've got to maintain them for 6-8 weeks until you can use them. That's >$1,000 in breeding costs before you get to the actual experiments.
So, let's say you need 20 female mice for an experiment (e.g. 4 groups of 5). That means that you need to have >40 offspring in order to get enough female offspring. That's at least 7 breeding pairs (assuming you're not harem breeding) and you've got to maintain them for 6-8 weeks until you can use them. That's >$1,000 in breeding costs before you get to the actual experiments.
But even after all that you're still at ">$50" per mouse. This isn't the part that makes a mouse cost 5 figures.
Adding to what josephpmay said, there's the issue of dealing genetic drift, so some groups have expensive-to-maintain systems to deal with that [0]. Which looks like restarting the line every 5 generations.
I have more experience with tissue culture than mice, but that's sounds surprisingly similar to passaging tissue cultures over and over [1]. Eventually you get to far out and have to start fresh, going back to stock cells.
[0] https://www.jax.org/jax-mice-and-services/find-and-order-jax...
[1] https://en.wikipedia.org/wiki/Immortalised_cell_line
I have more experience with tissue culture than mice, but that's sounds surprisingly similar to passaging tissue cultures over and over [1]. Eventually you get to far out and have to start fresh, going back to stock cells.
[0] https://www.jax.org/jax-mice-and-services/find-and-order-jax...
[1] https://en.wikipedia.org/wiki/Immortalised_cell_line
Having to start over every 5 generations doesn't explain very much, though. Sure, you have to do some very expensive things to make a batch, but then four generations at a low 80 babies per female gives you two and a half million mice. So what are the other factors?
(Never maintained a mouse colony before and rgejman had some good points. I've never done an experiment that used male mice before, for example.)
Just some random expenses I could think of:
1) Maintaining the material to restart the line itself is pretty expensive. Expensive equipment, regular quality control, the scientists doing this maintaining would be relatively expensive. 2) The $17000 referenced in the article are "CRISPR/Cas9 injection to obtain knockout founders" I think?) are custom designed genetically modified mice to start a colony with [0]. More standard human disease-relevant db/db mice (model for diabetes) that I've used before are $500/mouse, as a reference. 3) More cynically, the labs that can actually make use of those $17000 CRISPR/Cas founder mice probably have a continuous flow of millions in funding, so they can charge whatever they want.
[0] https://www.jax.org/news-and-insights/jax-blog/2017/march/li...
Just some random expenses I could think of:
1) Maintaining the material to restart the line itself is pretty expensive. Expensive equipment, regular quality control, the scientists doing this maintaining would be relatively expensive. 2) The $17000 referenced in the article are "CRISPR/Cas9 injection to obtain knockout founders" I think?) are custom designed genetically modified mice to start a colony with [0]. More standard human disease-relevant db/db mice (model for diabetes) that I've used before are $500/mouse, as a reference. 3) More cynically, the labs that can actually make use of those $17000 CRISPR/Cas founder mice probably have a continuous flow of millions in funding, so they can charge whatever they want.
[0] https://www.jax.org/news-and-insights/jax-blog/2017/march/li...
> custom designed genetically modified mice to start a colony with
Ah, the idea that this is the price before amortizing across thousands of mice is perfectly reasonable.
Ah, the idea that this is the price before amortizing across thousands of mice is perfectly reasonable.
Cockroaches escaped: https://www.telegraph.co.uk/news/worldnews/asia/china/102648...