
The Rogue Experimenters - mheuston
https://www.newyorker.com/magazine/2020/05/25/the-rogue-experimenters
======
highfrequency
> Anybody can go there to learn about, and then do, the kind of cutting-edge
> bench science—gene editing, synthetic biology—that is generally confined to
> well-funded academic institutions and private corporations.

Cool stuff! Can anyone who is more familiar comment on how "legit" these
biospaces actually are? I also had the vague sense that cutting-edge biology
is totally intractable outside of a very well-funded lab.

~~~
ampdepolymerase
Here we go again :) Let's see if HN will crucify me for daring to compare a
PCR machine to a slow cooker.

Also, look up OpenTrons. Lab automation is not glamorous work. There is no
huge consumer market like 3D printers and drones to help push the price down.
Even on the evangelism side, there has yet to be an "EEVBlog for
biotechnology" (the closest are Thought Emporium and Josiah Zayner's channel).
Perhaps this pandemic would change things. 80% of the expensive stuff are
mostly imaging or spectrometry related. Most of the remain 20% are expensive
because they are _niche and proprietary_ , not necessarily because they are
_hard_. There is no printer driver moment (Stallman et al.) to catalyze any
mass change because, well, the entire society that brought up the poor postdoc
using the printer sees nothing wrong in biomedical research being expensive
and gatekept and that postdoc him/herself is a product of that system,
otherwise he/she won't have made postdoc. A lot of things are niche and
expensive, just ask those who had to work on video protocols like AV1. Yet
they are available for free. There are a ton of biotechnology that requires,
to use a gaming slang, "grinding", but are a magnitude easier than good video
compression, instead they are all extremely out of reach for the casual
practitioner. Just google "basal cell media". It is bread and butter of many
labs but cost more than caviar. Think of bio instrumentation being like
obscure fintech time series databases. They are not necessarily more difficult
to build or engineer than anything else but are simply constrained by demand
hence ridiculous pricing.

As for legitimacy of hackerspaces, I will frame it through your lens (from
your username I am guessing that you are a quant). The FDA is essentially the
SEC of anything biomed related. However it is not a true free market in the
sense that anyone can enter. Hence legitimacy is a problem. The equivalent of
FINRA accreditation is a PhD and/or medical school. Small independent traders
are very much not a thing when it comes to biotech (which is what the various
movements mentioned in the article is trying to change). Also people like
Josiah Zayner are very unpopular because they upset the usual narrative about
biohackers being unaccredited "they know not what they do" and merely
attention-seeking stunt people.

If you want some reading resources that are hacker friendly, try this O'Reilly
book:

[http://shop.oreilly.com/product/0636920033783.do](http://shop.oreilly.com/product/0636920033783.do)

------
atemerev
I bought myself a used Stratagene MX4000 (а qPCR machine), found the drivers
and software (it is quite old), and now learning to run qPCR experiments,
particularly for coronavirus RNA detection (the primers, master mixes and
other consumables are available everywhere now — I am always telling every
biochemical supplier that I am a hobbyist researcher — no problems so far). It
is super fun.

~~~
rramadass
Nice! As a Software guy who is bored with "normal" software, i would be
interested in learning Biotech and the usage of Embedded Computing for the
same. Can you elaborate a little bit on what the machine is, what you do with
it and its potentialities for a total noob? Any books or other resources that
you would recommend?

------
ampdepolymerase
It sounds easy in theory but most people hate the idea of messing with
biology, believing that it should be regulated and professionalised as much as
possible. Even on this very forum, the mere suggestion that a PCR machine
(basically a glorified slow cooker) can be built with off the shelf parts is
enough to invite a flood of downvotes -
[https://news.ycombinator.com/item?id=22578216](https://news.ycombinator.com/item?id=22578216)

The lack of easy commercialisation of biotechnology and regulatory capture in
the name of "move fast break things and people die" has resulted in very poor
understanding of biochemistry among the general population (most advocates and
detractors of vaccines cannot explain how they work or don't work at the
chemical level, one of the reasons for the whole Thiomersal controversy). The
top minds who do go into this field often do so for the sake of medical
school, where the number of places are limited by politics and gatekeeping
rather than any practical meritocratic reason. The lack of money and
opportunity is a fundamental problem. Currently large numbers of the general
population have a damn good understanding of how computers work, thanks in
part due to web dev bootcamps and the rise of FAANG driving the industry. The
same cannot be said for biology or even organic chemistry. Bill Gates has
famously said that he would study biology if he was to go back to school
again, but in the current environment it would be doubtful any unicorn-level
of fast financial gains/reward can be achieved in biotechnology. He will most
likely end up as one of the numerous healthcare workers whose ultimate reward
after each day of dealing with a pandemic is orchestrated clapping instead of
spearheading vaccine research through his foundation (assuming of course he
had not already switched to working as a McKinsey consultant given his family
connections). Global pharmaceutical and healthcare research is still currently
led by the United States; FDA-approval being the universal standard. Sure
there are a couple EU-only projects and some attempts in Asia too, but the
world's biotech research and development still operates fundamentally within
the system of American capitalism. The dearth of opportunities due to
politics, regulatory capture, and general lack of appreciation of biology is
as much a tragedy as lack of health insurance. Most people would immediately
identify with or quote the various media talking points when it comes to
healthcare pricing, but hardly anyone would question why there are such
tremendous gatekeeping and lack of competition.

I will also link to my previous comment on this:
[https://news.ycombinator.com/item?id=22471482](https://news.ycombinator.com/item?id=22471482)

Giving up in the face of ignorance is not good policy so I will continue my
advocacy of more open biology and medical education even if my comments
succumb to the ego of software engineer hordes.

~~~
xkcd-sucks
All these points are correct.

But, to be fair, the state of the art in biology is still full of Magic and
other nonreproducible effects.

Computery people get annoyed if a compilation takes 10 minutes and fails with
a cryptic error message. Compare this to an experiment where (for example) you
spend a full day harvesting fetal rat hippocampus cells, cultivate them for
weeks, and then finally run your experiment which "fails". Did you fail the
rat prep? It worked for the wizard postdoc but she has been dissecting tiny
little hippocampi for years -- maybe the cells aren't what you think they are.
Or maybe, due to some unknown factor (temperature? feeding schedule? co2?
mycoplasma? ...), the cells are "unhappy" for... some reason . Etc. More of
the same, another month, another year, another replication which may or may
not be sufficient to quit the experiment altogether. The systems are not
understood well enough to debug; the systems which are easily debuggable are
not relevant to the real world. But, it is not difficult to do at home what
one does in an academic lab. (corporate labs have a bit more money which
shortens the iteration loop a bit but doesn't make it less cryptic)

Anecdotally, I got a life science PhD and went into a softwarey career because
the iteration loop of biology just plain sucks. When I was in grad school, I
had free reign to do absolutely whatever with no oversight (if the bills
looked normal) -- and did, for a while. All those cool ideas I had, I am
content to let other people have and realize them. I am content to read their
papers and to hire them.

~~~
dnautics
>But, to be fair, the state of the art in biology is still full of Magic and
other nonreproducible effects

No, it's not. It's full of things that have week long design cycles (instead
of a 200 ms compile loop) and are a pain, and lots of grad students that have
either never heard of design of experiments, or know about it and are
overeager to apply it. A friend worked at BP biofuels. The team kept waving
off irreproducibility as 'biology being strange'. For months she kept saying
"hey guys our feedstocks aren't defined". Then finally after a half a year
they caved and let her do her experiments, and sure enough there was a
limiting nutrient in the feedstock that correlated with the fluctuations. Then
a few months later the supreme court ruled against BP and the biofuel project
got cancelled.

I had a similar experience, and switching model organisms took my design cycle
from 2 weeks to two days, and got huge results out of it. We then put the
results back in the original organism and recapitulated the improvement. Then
my project got cancelled.

In the end though, it seems I'm better at software and it pays better.

~~~
highfrequency
> I had a similar experience, and switching model organisms took my design
> cycle from 2 weeks to two days, and got huge results out of it. We then put
> the results back in the original organism and recapitulated the improvement.
> Then my project got cancelled.

Very cool. If you care to elaborate on this: what were the two organisms, what
made the second amenable to much faster design cycles, and how did you know
that the results would likely carry over to the original organism?

~~~
dnautics
Slow organism was synechococcus, fast organism was E. Coli, original results
were highly likely to carry over since it was a fundamental alteration to the
enzyme function.

[https://pubmed.ncbi.nlm.nih.gov/23819621/](https://pubmed.ncbi.nlm.nih.gov/23819621/)

If you use the right tools and live in the right place you can get an e coli
design cycle down to 48 hours. In San Diego, i could design primers in the
afternoon, have them on my desk in the morning, do a pcr/Gibson assembly that
was done by lunch, pick colonies in the evening, miniprep and retransform
early the next day and have phenotypes soon after.

It's also robust. I trained an intern with only classroom experience in
molecular biology and he made 50 mutations and biochemically tested half over
the course of 10 weeks.

[https://pubmed.ncbi.nlm.nih.gov/24934472/](https://pubmed.ncbi.nlm.nih.gov/24934472/)

