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>Having studied biology and genetics this is common sense to me. Genetic systems are probabilistic chemical systems where everything influences everything to va

>Having studied biology and genetics this is common sense to me. Genetic systems are probabilistic chemical systems where everything influences everything to varying degrees in parallel. They are nothing like the linear assemblies of modules that humans prefer to engineer. I'm really glad that this mental model I've built up seems to reflect reality. The idea of neatly editing specific genes to produce a desired result always sat with me as the pinnacle of human hubris. The more I learn about Biology the more I just throw up my hands and say "magic".

bookofjoe 8y ago
>The idea of neatly editing specific genes to produce a desired result always sat with me as the pinnacle of human hubris. See, for example: Gene Therapy in a Patient with Sickle Cell Disease https://www.nejm.org/doi/full/10.1056/NEJMoa1609677 https://www.nejm.org/doi/full/10.1056/NEJMoa1609677
- aphextron 8y ago
  I literally can't understand a single word on that page. Care to explain?
  - bookofjoe 8y ago
    "We describe our first patient treated with lentiviral vector–mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells."
    - politician 8y ago
      "We describe our first patient treated with <a technique that injected> <DNA to counteract the disease> into <stem cells>. <which were then injected into the patient>."
      - bookofjoe 8y ago
        Or you could simply say "We performed a chemistry...":-)
bookofjoe 8y ago
From 2010: Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355472/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355472/
dekhn 8y ago
There are diseases for which editing a single gene in the right set of cells would absolutely cure a disease. There might be other genes or regulatory elements involved, but their contribution is neglible. To me, the pinnacle of human hubris is thinking you can correct the more challenging ones (like the ubergenetic phenotypes described here) without having some sort of powerful technology that helps work with the irreducible complexity of probabilistic chemical systems.
api 8y ago
Its not magic. Its just something we don't have good mental models for understanding since it doesn't resemble the things we usually engineer. I always give the following rough analogy: "Imagine a programming language where every single instruction simultaneously executes and simultaneously alters the inputs of all other instructions to varying degrees." Complex artificial neural networks and data flow models are closer to gene regulatory networks and the genotype->ribotype->phenotype causal flow but are still oversimplifications. It is sometimes possible to hack individual genes to fix really glaring problems reducible to one or a few key mutations like sickle cell anemia. Those things are the low hanging fruit of genetic engineering. Beyond that it gets harder. Trying to do things like boost life span or median IQ will be exponentially harder and will require new cognitive paradigms IMHO. Its too bad nobody studies this stuff anymore. There was a ton of really great research into complex systems and emergent behaviors in the 90s and 2000s and then it went out of vogue for some reason.
perl4ever 8y ago
Is it really magic or is the genetic code just defining something much more like a CPU or OS than an application program? If you took a bug report and did a statistical analysis of what transistors contributed to the bug, in most cases it would tell you "pretty much all of them". In very rare cases, it would tell you there were specific broken transistors. Similar for OS instructions. Because it's just the wrong level to be analyzing problems with the ultimate behavior of a system that's mostly functional. 99.9999% of the time, you don't have a compiler bug or an OS bug or a hardware bug, because if you did, everything would be dead. My kneejerk reaction* is that genes are like transistors or OS instructions and not like application program instructions, and it really shouldn't be surprising or mysterious if they don't correspond to specific behaviors. It's just a different level of abstraction. *having not studied biology and genetics, and just assuming living organisms have to be like computers.
- saalweachter 8y ago
  The closest analogy in technology would be the Internet, IMO. A CPU or a single computer is still a fairly homogeneous, consistent creation. Sure, it has a lot of transistors, but it's just the same pattern over and over. Think about the Internet: many of the billions of things on the internet are similar enough to be called the same, but many of them are ... a little not. This computer is Intel, this is AMD. This one runs Microsoft, this one Ubuntu. This one Ubuntu 15.07 with a 5.3.2.2 Linux kernel, that one with a 5.3.7.1 kernel. This part uses IPv4, that IPv6. This HTML on this site is a little nonstandard, that one relies on an expired SSL certificate. The body, and modifying it, is a lot like the Internet. You set up 1.1.1.1 as a DNS server and accidentally partition the Internet.

bookofjoe 8y ago

>The idea of neatly editing specific genes to produce a desired result always sat with me as the pinnacle of human hubris. See, for example: Gene Therapy in a Patient with Sickle Cell Disease https://www.nejm.org/doi/full/10.1056/NEJMoa1609677 https://www.nejm.org/doi/full/10.1056/NEJMoa1609677

aphextron 8y ago
I literally can't understand a single word on that page. Care to explain?
- bookofjoe 8y ago
  "We describe our first patient treated with lentiviral vector–mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells."
  - politician 8y ago
    "We describe our first patient treated with <a technique that injected> <DNA to counteract the disease> into <stem cells>. <which were then injected into the patient>."
    - bookofjoe 8y ago
      Or you could simply say "We performed a chemistry...":-)

bookofjoe 8y ago

From 2010: Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355472/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355472/

dekhn 8y ago

There are diseases for which editing a single gene in the right set of cells would absolutely cure a disease. There might be other genes or regulatory elements involved, but their contribution is neglible. To me, the pinnacle of human hubris is thinking you can correct the more challenging ones (like the ubergenetic phenotypes described here) without having some sort of powerful technology that helps work with the irreducible complexity of probabilistic chemical systems.

api 8y ago

Its not magic. Its just something we don't have good mental models for understanding since it doesn't resemble the things we usually engineer. I always give the following rough analogy: "Imagine a programming language where every single instruction simultaneously executes and simultaneously alters the inputs of all other instructions to varying degrees." Complex artificial neural networks and data flow models are closer to gene regulatory networks and the genotype->ribotype->phenotype causal flow but are still oversimplifications. It is sometimes possible to hack individual genes to fix really glaring problems reducible to one or a few key mutations like sickle cell anemia. Those things are the low hanging fruit of genetic engineering. Beyond that it gets harder. Trying to do things like boost life span or median IQ will be exponentially harder and will require new cognitive paradigms IMHO. Its too bad nobody studies this stuff anymore. There was a ton of really great research into complex systems and emergent behaviors in the 90s and 2000s and then it went out of vogue for some reason.

perl4ever 8y ago

Is it really magic or is the genetic code just defining something much more like a CPU or OS than an application program? If you took a bug report and did a statistical analysis of what transistors contributed to the bug, in most cases it would tell you "pretty much all of them". In very rare cases, it would tell you there were specific broken transistors. Similar for OS instructions. Because it's just the wrong level to be analyzing problems with the ultimate behavior of a system that's mostly functional. 99.9999% of the time, you don't have a compiler bug or an OS bug or a hardware bug, because if you did, everything would be dead. My kneejerk reaction* is that genes are like transistors or OS instructions and not like application program instructions, and it really shouldn't be surprising or mysterious if they don't correspond to specific behaviors. It's just a different level of abstraction. *having not studied biology and genetics, and just assuming living organisms have to be like computers.

saalweachter 8y ago
The closest analogy in technology would be the Internet, IMO. A CPU or a single computer is still a fairly homogeneous, consistent creation. Sure, it has a lot of transistors, but it's just the same pattern over and over. Think about the Internet: many of the billions of things on the internet are similar enough to be called the same, but many of them are ... a little not. This computer is Intel, this is AMD. This one runs Microsoft, this one Ubuntu. This one Ubuntu 15.07 with a 5.3.2.2 Linux kernel, that one with a 5.3.7.1 kernel. This part uses IPv4, that IPv6. This HTML on this site is a little nonstandard, that one relies on an expired SSL certificate. The body, and modifying it, is a lot like the Internet. You set up 1.1.1.1 as a DNS server and accidentally partition the Internet.