
Demand is skyrocketing in China for mice that mimic the diseases of humans - pseudolus
https://www.bloomberg.com/news/articles/2019-04-01/china-s-demand-for-17-000-gene-altered-lab-mice-is-skyrocketing
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wiradikusuma
What would happen if the mice escaped the facility, and bite other animals or
humans (or breed with 'normal' mice)?

Cockroaches escaped:
[https://www.telegraph.co.uk/news/worldnews/asia/china/102648...](https://www.telegraph.co.uk/news/worldnews/asia/china/10264868/One-
million-cockroaches-escape-from-Chinese-farm.html)

~~~
Sammi
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.

~~~
cat199
> 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

~~~
el_cujo
>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.

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londons_explore
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.

~~~
rgejman
>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](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.

~~~
dmix
(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.

~~~
rgejman
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.

~~~
dmix
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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londons_explore
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?

~~~
sndean
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...](https://www.jax.org/jax-mice-and-services/find-and-order-jax-mice/why-
jax-mice/patented-genetic-stability-program)

[1]
[https://en.wikipedia.org/wiki/Immortalised_cell_line](https://en.wikipedia.org/wiki/Immortalised_cell_line)

~~~
Dylan16807
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?

~~~
sndean
(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...](https://www.jax.org/news-and-insights/jax-
blog/2017/march/life-after-crispr)

~~~
Dylan16807
> 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.

