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The early pioneers in genetics were all consummate hackers in the truest sense. For much of the work they were doing, the had very little information about the

The early pioneers in genetics were all consummate hackers in the truest sense. For much of the work they were doing, the had very little information about the underlying processes to go on. The were, in effect, reverse engineering life. It's also worth noting that Sanger's sequencing method, or variations on it, were still used decades later to produce the bulk of the human genome sequence. Only very recently have newer, faster, alternative methods been developed. Even so, Sanger sequencing is still used for smaller scale studies, and is simple enough that almost any modern biology lab can do it on their own (all you need is a thermocycler, some eppindorfs, a sequencing gel apparatus, some photographic film, and all the raw chemicals).

dnautics 13y ago
although you're better off doing sanger by contract. Sanger sequencing costs about $3 a run for really reliable sequencing. Contemporary sanger will likely never be obsolete because for short runs ~1kb where you need to be ~100% sure there are no mistakes, the method is really unbeatable.
drcode 13y ago
> All you need is a thermocycler, some eppindorfs, a sequencing gel apparatus, some photographic film, and all the raw chemicals. And brutal amounts of tedious, flawless precision (I have tremendous respect for people who can do this stuff...)
- jballanc 13y ago
  ...also known as graduate school. ;-) Seriously, though, my wife used to work with alternative RNA bases. Localizing them to specific sequences required the most massive sequencing gels I've seen (at least 1m tall), and every surface in the lab had to be continually rinsed with dilute acid. It turns out, human skin contains bucket-loads of non-specific RNAses. Not a problem for most people who work with DNA, but can absolutely ruin a week or more's worth of work if you're in an RNA lab.
  - dekhn 13y ago
    The best way to think about life is: RNA is one true source of life activity. Everything else: DNA, proteins, carbohydrates and membranes are just things that RNA decorates itself with to minimize degradation by other RNAs, which are trying their best to cut your RNA into little pieces. That's why you have to be so careful: life tries very hard to keep the wrong RNAs out.
    - hughlomas 13y ago
      DNA is the hereditary material, RNA isn't "decorating itself" with DNA.
      - dekhn 13y ago
        You're taking my use of the term decorating too literally. In the case of DNA I meant that RNA likely began to delegate the heredity function to DNA since it was much polymers were more stable at room temperature and it was less likely to form complex 3D structures.
        drcode 13y ago
        agreed- DNA is a puppet, RNA is the puppet master.
bionerd 13y ago
> The early pioneers in genetics were all consummate hackers in the truest sense. For much of the work they were doing, the had very little information about the underlying processes to go on. Exactly! They only had the most basic tools (even primitive by today's standards!) at their disposal and were still able to discover the most profound and fascinating things about life at the molecular level. All that using only a few simple techniques and a pure deductive logic. It never ceases to amaze me how much hacker spirit these people had.
- dekhn 13y ago
  When I first learned about molecular biology (late 80s, while in high school), I immediately shifted my interest from just computers to computers and biology. I specifically told people at the time: "studying molecular biology is like being put in front of the world's largest and most complicated computer and being told 'we have no manual, and do not know how it even works, could you figure out by playing with it?' It took many years for me to reconcile my hacker approach to life with the reality of scientific funding and the rate of progress in human diseases.
  - bionerd 13y ago
    My story is very similar. After high school I went to study computer science in college. Then, just before I got my bachelor's degree, I decided to apply to a programme in molecular biology instead of further pursuing master's degree in computer science. Switching gears was the best decision of my life. I've never had so much fun as I had while attending the introductory lectures in cell or molecular biology. So many mind-blowing things I never would've imagine... Now I'm hoping to get into a PhD programme in genetics. Can't wait to learn about other amazing stuff waiting out there. :)
    - dnautics 13y ago
      I'm on the other side. I have a PhD in chemistry, can do molecular biology, biochemistry - the wet parts, and I am on my last breath with science. Since I can write computer software, (not too terribly disciplined, industrial-wise, at this point, but I can learn), if my attempt to launch a nonprofit research institute fails, I'm going to quit and go into the digital world. Perhaps the grass is always greener, but I have strong words about what is wrong with science, and if you want to know, feel free to contact me.

dnautics 13y ago

although you're better off doing sanger by contract. Sanger sequencing costs about $3 a run for really reliable sequencing. Contemporary sanger will likely never be obsolete because for short runs ~1kb where you need to be ~100% sure there are no mistakes, the method is really unbeatable.

drcode 13y ago

> All you need is a thermocycler, some eppindorfs, a sequencing gel apparatus, some photographic film, and all the raw chemicals. And brutal amounts of tedious, flawless precision (I have tremendous respect for people who can do this stuff...)

jballanc 13y ago
...also known as graduate school. ;-) Seriously, though, my wife used to work with alternative RNA bases. Localizing them to specific sequences required the most massive sequencing gels I've seen (at least 1m tall), and every surface in the lab had to be continually rinsed with dilute acid. It turns out, human skin contains bucket-loads of non-specific RNAses. Not a problem for most people who work with DNA, but can absolutely ruin a week or more's worth of work if you're in an RNA lab.
- dekhn 13y ago
  The best way to think about life is: RNA is one true source of life activity. Everything else: DNA, proteins, carbohydrates and membranes are just things that RNA decorates itself with to minimize degradation by other RNAs, which are trying their best to cut your RNA into little pieces. That's why you have to be so careful: life tries very hard to keep the wrong RNAs out.
  - hughlomas 13y ago
    DNA is the hereditary material, RNA isn't "decorating itself" with DNA.
    - dekhn 13y ago
      You're taking my use of the term decorating too literally. In the case of DNA I meant that RNA likely began to delegate the heredity function to DNA since it was much polymers were more stable at room temperature and it was less likely to form complex 3D structures.
      - drcode 13y ago
        agreed- DNA is a puppet, RNA is the puppet master.

bionerd 13y ago

> The early pioneers in genetics were all consummate hackers in the truest sense. For much of the work they were doing, the had very little information about the underlying processes to go on. Exactly! They only had the most basic tools (even primitive by today's standards!) at their disposal and were still able to discover the most profound and fascinating things about life at the molecular level. All that using only a few simple techniques and a pure deductive logic. It never ceases to amaze me how much hacker spirit these people had.

dekhn 13y ago
When I first learned about molecular biology (late 80s, while in high school), I immediately shifted my interest from just computers to computers and biology. I specifically told people at the time: "studying molecular biology is like being put in front of the world's largest and most complicated computer and being told 'we have no manual, and do not know how it even works, could you figure out by playing with it?' It took many years for me to reconcile my hacker approach to life with the reality of scientific funding and the rate of progress in human diseases.
- bionerd 13y ago
  My story is very similar. After high school I went to study computer science in college. Then, just before I got my bachelor's degree, I decided to apply to a programme in molecular biology instead of further pursuing master's degree in computer science. Switching gears was the best decision of my life. I've never had so much fun as I had while attending the introductory lectures in cell or molecular biology. So many mind-blowing things I never would've imagine... Now I'm hoping to get into a PhD programme in genetics. Can't wait to learn about other amazing stuff waiting out there. :)
  - dnautics 13y ago
    I'm on the other side. I have a PhD in chemistry, can do molecular biology, biochemistry - the wet parts, and I am on my last breath with science. Since I can write computer software, (not too terribly disciplined, industrial-wise, at this point, but I can learn), if my attempt to launch a nonprofit research institute fails, I'm going to quit and go into the digital world. Perhaps the grass is always greener, but I have strong words about what is wrong with science, and if you want to know, feel free to contact me.