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Comment by joe_the_user | Hacker News Reader

The article gives the impression that a lot of biology involves ad-hoc, artisanal techniques that have been somewhat standardized and automated over the years. And that the standardization and automation involved can actually stand in the way of changing an approach.

There was an article about the standardization of laboratory mice - it allows large scale, reproducible results but guarantees you won't things that can't be learned from the single, genetically uniform mouse type that is used.

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>guarantees you won't things that can't be learned from the single, genetically uniform mouse type that is used.

This is a misrepresentation of the state of mouse biology research.

We use many different strains of inbred mice (check out the JAX Labs list of available inbreds)[1]. Inbreeding reduces the genetic variability of our mice, allowing us to control more of the variation in an experiment. This allows us to perform pilot studies with smaller samples sizes while still reaching sufficient statistical power. This is important -- mouse biology is expensive, and we try to discover as much as possible with limited funding.

If a result merits generalization to multiple backgrounds, it is often tested in multiple inbred strains and an "outbred" strain that is genetically diverse.

[1] - https://www.jax.org/jax-mice-and-services/find-and-order-jax...

I think you're confusing my comment, which addresses the inherent limitation of automating particular experimental processes with a criticism about how biological research ought to be conducted. It may well be that uniformity is needed for reproducibility - even adding more controls for the uniformity, biology seems broadly limited by a relatively few particular starting points. As the OP points out, because the vast diversity of biological phenomena, it seems there are variety of things that simply aren't seen with only these starting points (again, not to deny that as practical matter one might still need to limit one's starting points).

Currently our understanding of biochemistry is so poor that we still have a lot to learn about the very basics. I don't think the diversity of our lab mice is currently a limiting factor.

Our understanding of biochemistry is actually quite good, it is our understanding of biochemistry diversity that is poor (i.e. why are you and I different). Using inbred mice does not help solve this problem.

I'm no expert, but it seems to me that as long as there is still basic research being done on the behavior of very simple proteins, we're a long way from understanding the complex interactions that happen in cells.

Yes we have a lot to learn about all the interactions between proteins in a cell, but this typically does not fall under the heading of biochemistry.

Slightly off topic the traditional divisions between different areas of biological sciences that built up in the 20th C have all broken down with the rise of molecular biology. Once biochemistry was a different field to say microbiology, now both are part of the super-field of molecular sciences.

The important practical results (e.g. many particular drugs) that we get and need are obtained not because of understanding why they work but despite that, empirical testing is a key part of current process.

We have considered and discarded a lot of candidate drugs with great potential before starting human testing. As a rule, if some molecule would cure an important disease but for whatever reason doesn't work on the popular strains of mice, then our current process would cause us to discard it.

I would like to see inbred mice banned from all research not about inbreding. No study should use inbred mice - sure is lets you use less mice, but at the expense of generating results that are limited to one individual. If we can't afford to use outbred mice then we should not have done the experiment.

The use of inbred animals isn't a cost saving technique. Inbred strains are developed over many generations so that individuals are genetically homogeneous. You know that any different results you get are due to different treatments for instance rather than the genetic background of the animals you're using.

>"You know that any different results you get are due to different treatments for instance rather than the genetic background of the animals you're using."

I don't think this is really true. Perhaps that makes it unlikely genetic differences are the cause of a relatively large apparent treatment effect, but not just any difference.

Yes it is. Using inbred mice allows you to use fewer mice as the variability due to the genetic background is reduced. The more variability in your system the more individuals you need to see a statistically valid difference due to treatment. The more you have to test the more the cost.

None of this would matter if we were developing cures for diseases of C57BL/6 mice [1], but we are actually interested in developing cures for humans who are not inbred (well in most places). We need our animals models to match as closely as possible to humans and using inbred mice is not a good match.

1. https://en.wikipedia.org/wiki/C57BL/6

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