3 ms·

What? This is so very wrongheaded. We learned quickly that 'cancer' is to the twentieth century 'the fevers'. We learned there are many reasons and causes for

by toufka 10y ago

What? This is so very wrongheaded. We learned quickly that 'cancer' is to the twentieth century 'the fevers'. We learned there are many reasons and causes for the catch-all, 'cancer'. Some we now know how to cure effectively. Some we now now how to prevent, effectively. Some we now know what to do to cure, but don't have good tools yet. And many we still do not understand. That is a significant improvement in a very short time span. But there's a LOT more to learn than 'how to cure cancer'. We very clearly understand gene expression and signal transaction to a first order, and have bits of the second order down too. There might be more - but that doesn't make that first order inneffective or wrong. There's lots you can do with a first order understanding - see what Newtonian physics did for the world - it was correct only to the first order. The idea that we know 'fuck-all' about biology because of dna sequencing is just ridiculous. The ability to read and write dna is fueling one of the fastest growing segments of human progress today.

astazangasta 10y ago
We didn't learn any of those things because of genomics. The major cancer therapies of today were developed before short read sequencing was even a thing; cancer researchers been saying for decades that cancer is "not one disease". In fact the genomics efforts were largely intended to overturn that wisdom by using genetic lesions to unify disparate cancer types (to little avail). About the only really interesting thing we learned from these recent efforts is that tumors are a lot more genetically heterogeneous than we previously appreciated, which just expands the problem space. The proof in the pudding is this: you can get your exome sequenced today and report hundreds of tumor variants, but there is a bare handful of variants that will result in a change in your treatment, and most of those lesions were well-studied before genomics took off. >We very clearly understand gene expression and signal transaction to a first order, and have bits of the second order down too. There might be more - but that doesn't make that first order inneffective or wrong. Yes, in fact, our first order understanding IS ineffective. This is what I study every day, so perhaps I'm too close to this, but we literally do not understand the effect of most (99.9%) of genetic variants on gene expression. Sure, there's lots you can do with a first order understanding, but materially, what happens when you sequence a tumor (or a germline, for that matter), is that researchers get a list of mutations, stare at it mystified for a while, and then shrug and move on, because there's really nothing you can do to understand what these things mean. Yes, this stuff is the way of the future, and it's important to do it for our greater knowledge and understanding in the future. But we're far, far away from this point right now.
- toufka 10y ago
  I think your point is accurate, but jaded. Much as the above posters point out, there was no sudden 'click' where an individual discovered something and made genomics possible. And to the extent that's what we mean by 'genome sequencing', then you are correct - the shotgun approach coupled with big-data hasn't been very useful yet. However, if the message is more one of genetics at large, and how the ability to read/write DNA has affected our research, our discoveries, our therapeutics, and will affect our lives in the near-future, then your tone seems entirely too myopic. Nearly every drug you see on TV commercials today is a monoclonal antibody - which cannot have been made but for the ability to read and write DNA. Sure, it doesn't require the ability to read an entire animals' DNA at once (do the full genome sequences yet actually read every base in your genome even?). But it is a very real and very finite milestone on that exact same path. You are correct, genomic ≠ genetic, but in so far as they are similar (mostly), our understanding of genetics really has been a powerful driver in the past two to three decades.
  - astazangasta 10y ago
    Of course I recognize the potential of this technology; I wouldn't be in this field otherwise. And I probably am jaded, because I think people are constantly overemphasizing and overplaying our understanding of things in order to sound sexy and attract funding. I think there's probably a fifteen-year lag in this stuff being useful. The insights we're having now are because of the sequencing of the human genome; the work we're doing now will pay off in another decade and a half when we've figured out how to deal with gene expression. >do the full genome sequences yet actually read every base in your genome even? Read, sequence: yes. Align: no.

by toufka 10y ago

astazangasta 10y ago

We didn't learn any of those things because of genomics. The major cancer therapies of today were developed before short read sequencing was even a thing; cancer researchers been saying for decades that cancer is "not one disease". In fact the genomics efforts were largely intended to overturn that wisdom by using genetic lesions to unify disparate cancer types (to little avail). About the only really interesting thing we learned from these recent efforts is that tumors are a lot more genetically heterogeneous than we previously appreciated, which just expands the problem space. The proof in the pudding is this: you can get your exome sequenced today and report hundreds of tumor variants, but there is a bare handful of variants that will result in a change in your treatment, and most of those lesions were well-studied before genomics took off. >We very clearly understand gene expression and signal transaction to a first order, and have bits of the second order down too. There might be more - but that doesn't make that first order inneffective or wrong. Yes, in fact, our first order understanding IS ineffective. This is what I study every day, so perhaps I'm too close to this, but we literally do not understand the effect of most (99.9%) of genetic variants on gene expression. Sure, there's lots you can do with a first order understanding, but materially, what happens when you sequence a tumor (or a germline, for that matter), is that researchers get a list of mutations, stare at it mystified for a while, and then shrug and move on, because there's really nothing you can do to understand what these things mean. Yes, this stuff is the way of the future, and it's important to do it for our greater knowledge and understanding in the future. But we're far, far away from this point right now.

toufka 10y ago
I think your point is accurate, but jaded. Much as the above posters point out, there was no sudden 'click' where an individual discovered something and made genomics possible. And to the extent that's what we mean by 'genome sequencing', then you are correct - the shotgun approach coupled with big-data hasn't been very useful yet. However, if the message is more one of genetics at large, and how the ability to read/write DNA has affected our research, our discoveries, our therapeutics, and will affect our lives in the near-future, then your tone seems entirely too myopic. Nearly every drug you see on TV commercials today is a monoclonal antibody - which cannot have been made but for the ability to read and write DNA. Sure, it doesn't require the ability to read an entire animals' DNA at once (do the full genome sequences yet actually read every base in your genome even?). But it is a very real and very finite milestone on that exact same path. You are correct, genomic ≠ genetic, but in so far as they are similar (mostly), our understanding of genetics really has been a powerful driver in the past two to three decades.
- astazangasta 10y ago
  Of course I recognize the potential of this technology; I wouldn't be in this field otherwise. And I probably am jaded, because I think people are constantly overemphasizing and overplaying our understanding of things in order to sound sexy and attract funding. I think there's probably a fifteen-year lag in this stuff being useful. The insights we're having now are because of the sequencing of the human genome; the work we're doing now will pay off in another decade and a half when we've figured out how to deal with gene expression. >do the full genome sequences yet actually read every base in your genome even? Read, sequence: yes. Align: no.