Progress in Biology Is Slow – Here's How We Can Speed It Up • Hacker News Board

Re: Progress in Biology Is Slow – Here's How We Can Speed It Up

#21

Post by dekhn » Thu, Oct 01, 2020, 3:20 PM UTC

bsder wrote: post #18

peterlk wrote: post #3

> If we care about blood pressure, for example, why have we not given every drug, at every dosage, every regiment, and in every combination to a mouse and actually seen what happens? One of the answers is hidden behind this question: Ethics. We could make a ton of progress if we started growing humans for lab testing. Then we could run massively parallel tests and get data much quicker. I mean, think about how much w…

> If we're talking about biology in general, though, I think we have made enormous progress in the last 10-20 years. And, funnily enough, this corresponds with PCR becoming commonplace. I would argue that the lack of progress in biology was almost solely due to the fact that before PCR biology was effectively "alchemy" and that after PCR biology became "science". PCR and sequencing blew away entire subfields of biolo…

I'm not sure what you're talking about. PCR is a great technique, and sequencing has revolutionized biology, but it didn't go and blow away subfields of biology as being testably untrue.

Re: Progress in Biology Is Slow – Here's How We Can Speed It Up

#22

Post by rleigh » Thu, Oct 01, 2020, 5:01 PM UTC

taejo wrote: post #19

bsder wrote: post #18

Earlier quoted context omitted.

> If we're talking about biology in general, though, I think we have made enormous progress in the last 10-20 years. And, funnily enough, this corresponds with PCR becoming commonplace. I would argue that the lack of progress in biology was almost solely due to the fact that before PCR biology was effectively "alchemy" and that after PCR biology became "science". PCR and sequencing blew away entire subfields of biolo…

> PCR and sequencing blew away entire subfields of biology as being testably untrue. As a non-biologist I would love to hear of some examples of this

As a PhD biologist I'd love to hear some examples of this.

PCR is a great tool, and it's absolutely been a transformative research tool. But it's just one tool out of a catalogue of many others. It can't answer all questions. Genes and gene expression are just one part of a much bigger picture, and there are many other techniques which are just as relevant for exploring biological systems.

You rarely see PCR used in a research project in isolation. It's just one tool amongst many others, and for the most part you can't just look at gene expression and assume it has any functional effect. You've also got to demonstrate the downstream effect through other techniques, such as Western blotting, ELISA, LCMS and others, and even then you have to show that the expression products themselves also have an observable functional effect.

Re: Progress in Biology Is Slow – Here's How We Can Speed It Up

#23

Post by dekhn » Thu, Oct 01, 2020, 6:35 PM UTC

fabian2k wrote: post #6

The possible chemical space is incredibly vast. Even a large collections of potentially interesting molecules at hundreds of thousands or millions of molecules isn't even scratching the surface. Going directly to mice is certainly problematic in an ethical terms, you're going to kill many millions of mice for something that has very low odds of succeeding. Biological systems are noisy, the chance that one of your hit…

it's kind of impressive how, even those chemical space is vast, humans discovered salicylic acid from willow bark is a successful painkiller without ever running clinical trials or searching 1060 space.

Or how many chemicals we have were originally derived from plants. I wonder how they're finding these molecules without searching 1060 space?

Re: Progress in Biology Is Slow – Here's How We Can Speed It Up

#24

Post by bsder » Fri, Oct 02, 2020, 2:34 AM UTC

dekhn wrote: post #21

bsder wrote: post #18

Earlier quoted context omitted.

> If we're talking about biology in general, though, I think we have made enormous progress in the last 10-20 years. And, funnily enough, this corresponds with PCR becoming commonplace. I would argue that the lack of progress in biology was almost solely due to the fact that before PCR biology was effectively "alchemy" and that after PCR biology became "science". PCR and sequencing blew away entire subfields of biolo…

I'm not sure what you're talking about. PCR is a great technique, and sequencing has revolutionized biology, but it didn't go and blow away subfields of biology as being testably untrue.

Cellular immunology--a big debate in the 1970s was whether cells primarily recognize self or non-self. Sequencing completely smashed the non-self people.

The Tree of Life--entire species had to get transferred around due to sequencing.

There are other areas of biology as well that simply got nuked once you could sequence things accurately.

We forget about them because it's been about 30 years (one tenure length) since PCR and sequencing became commonplace.

Re: Progress in Biology Is Slow – Here's How We Can Speed It Up

#25

Post by rleigh » Fri, Oct 02, 2020, 10:06 AM UTC

bsder wrote: post #24

dekhn wrote: post #21

Earlier quoted context omitted.

I'm not sure what you're talking about. PCR is a great technique, and sequencing has revolutionized biology, but it didn't go and blow away subfields of biology as being testably untrue.

Cellular immunology--a big debate in the 1970s was whether cells primarily recognize self or non-self. Sequencing completely smashed the non-self people. The Tree of Life--entire species had to get transferred around due to sequencing. There are other areas of biology as well that simply got nuked once you could sequence things accurately. We forget about them because it's been about 30 years (one tenure length) sinc…

While the power of PCR isn't in question, I think you're overstating the case at bit. It didn't "nuke" whole areas of Biology, but it did add clarity and it did answer questions which previously were hard or impossible to answer using other techniques.

I think you're being somewhat unfair about taxonomy. Before whole-organism sequencing, classifying based upon detailed physical characteristics was the only option available, and for the most part that classification did match the genetic data. Sequencing did correct some mistakes, of course, but I think it does a disservice to all the people who did highly-detailed and rigorous work in that field to claim it was "nuked" when that simply is not the case. PCR-based sequencing did not invalidate most of our existing knowledge, but it did make it a quantitative science rather than qualitative.

Consider also that PCR also brought with it a number of problems of its own. Classification based upon sequencing of individual genes also led to mistakes because it didn't account for xenologues or independent evolution of the same mutation. These were later corrected with the advent of whole-genome sequencing and comparison of multiple genes. It also led to a lot of research published demonstrating that the presence of certain genes or expression products correlated with certain outcomes. And a huge amount of that was completely false, because they failed to investigate the downstream effect of these differences. In too many cases, there wasn't any functional effect, or the wrong conclusion was drawn because of experimental error and bad statistics. The bar for publishing in a good journal is now much higher, but it's still all to easy to misinterpret genetic data.

Re: Progress in Biology Is Slow – Here's How We Can Speed It Up

#26

Post by dekhn » Fri, Oct 02, 2020, 1:51 PM UTC

bsder wrote: post #24

dekhn wrote: post #21

Earlier quoted context omitted.

I'm not sure what you're talking about. PCR is a great technique, and sequencing has revolutionized biology, but it didn't go and blow away subfields of biology as being testably untrue.

Cellular immunology--a big debate in the 1970s was whether cells primarily recognize self or non-self. Sequencing completely smashed the non-self people. The Tree of Life--entire species had to get transferred around due to sequencing. There are other areas of biology as well that simply got nuked once you could sequence things accurately. We forget about them because it's been about 30 years (one tenure length) sinc…

You're definitely overstating the case. I don't forget about this stuff, since I was getitng my undergrad, grad, phd and postdoctoral work in this field.