

Synthetic Biology: Engineering Open-Source Software with DNA - mgh2
http://blog.drchrono.com/2012/06/11/synthetic-biology-enginnering-software-with-dna/

======
stiff
First, DNA is not software and second, before we all get too excited about
"Arudino for organisms", have a look at the actual parts:

<http://partsregistry.org/Catalog>

The biological world is very different from the world of man-made devices and
you cannot expect to easily engineer, and even more so, to "program" things
using DNA the way you build something from NAND gates or computer instructions
- in engineering we strive very hard to make parts independent and abstract
away low-level details, in biology everything is interacting all the time
(even physically the molecules clash hundreds of times per second) and every
low-level physical/chemical effect might be used to serve some purpose.
Evolutionary "design" does not have any limits to the intellectual complexity
of its results like our limited human intelligence forces us to have in our
"purposeful" design process.

Even predicting the outcome of a single gene being expressed is very
complicated, protein folding is now a separate field putting our knowledge of
physics, chemistry, biology and computer science to a test, and what to say
about predicting the interactions of those proteins inside the human body. I
wish people would take a good university-level biology 101 course before
making nonsensical simplifications and spreading those as "science news".

By the way, I do not doubt this is an interesting initiative and that some
useful things will come out of it, I just strongly oppose the notion that we
can all now "play with nature’s design".

~~~
jostmey
I totally agree with this! I wish we could "play with nature's design" like we
can program computers. But alas, our technology is woefully inadequate for the
task, and our understanding of the natural world is still sadly primitive.
What is needed is a generation of people willing to commit themselves to basic
science research.

Working in basic science is perhaps not as glamorous as working as an
entrepreneur, a programmer, or whatever else. But over the course of a
lifetime, the work is infinitely more satisfying.

~~~
tempuser007
"our understanding of the natural world is still sadly primitive" You are
talking for yourself ? For humanity ? For scientists you never met ? I
honestly don't know who you are and how well suited are you (you're a
specialist in bioengineering ?) to tell us how much "we" know or we don't. I'm
just a software engineer with some basic understanding of genetic engineering,
but my wife is a genetic technician in a lab, and it's amazing what operations
they performed on a daily basis as part of their university classes and
recently in research projects in real labs (and this didn't start yesterday or
only with my wife's generation). So I'm very tempted to believe that you just
woke up speaking about some limitations you don't personally know and it's not
even in your area of expertise. This does not mean that today "everything" is
possible or that we achieved the grand mastery of DNA. It's just that for the
"right people" the understanding of the natural world is more advanced than
you have ever dreamed (unless you are one of the "right people").

~~~
refurb
Let me give you the best example I can.

Computation chemistry has been going on for decades. Attempts at modeling how
molecules behave is still quite primitive. We're talking about modelling the
behavior of a object that is comprised of a few dozen atoms. That's it, pretty
simple right? We'll the models aren't that good at predicting molecular
behavior.

Let's move up a step now. Computation chemistry is used heavily by the drug
industry. Get an x-ray structure of a protein (maybe a few hundred to a few
thousand atoms) and see if it binds to a drug. Wow, now it's getting
complicated. How successful is it? Not very. I can remember a computational
chemist saying "oh hey, the model say if you replace X with Y, you'll increase
binding by 10x". So we try and guess what? The binding was worse.

Now we move up to a biological system. Now we have hundreds (if not thousands)
of proteins floating in a matrix of water and ions. We have a DNA strands of
millions of base pairs, of which maybe 10% we actually know what they do. We
also have small signalling molecules that do something we understand, but
probably also do 10 other things we have no idea about.

It is very impressive how far biological "design" (genomics) has come so far,
but right now the tools are incredibly blunt and the analysis is incredibly
crude. I have no doubt our understanding will improve immensely over the
coming decades, but I would guess we understand less than 1% of what's going
on inside of complex living organisms.

~~~
tempuser007
You see, my feeling is that trying to guess the progress of genetics by
extrapolating the complexity and insecurity of the computation chemistry is
wrong. As far as I understood, genetics today is a lot about (but not only)
identifying which genes (portions of DNA) are responsible of which phenotype
(en.wikipedia.org/wiki/Phenotype).Therefore a lot of resources are and were
allocated to create a dictionary with genes as keys and phenotype as values.
This dictionary is being populated at a quite fast pace and this combined with
the possibility to take genes from some organisms and implant them in the DNA
of a cell of other organisms and see the resulting phenotype is already a
great achievement (imagine undergrads cutting and pasting DNA daily). They are
not inventing new proteins and worry that they will not "bind" enough. They
just take the DNA known to produce proteins in some organisms and place it in
other organisms and suddenly proteins which have a known effect in different
organisms, appear in a new organism. Yes, there is a long way from here to
engineering genes that will produce and deliver a medicine inside an organism
but I wouldn't call this primitive at all. Sorry for the simplification and
possible errors.

~~~
refurb
OK, I see your perspective now. I agree that our understanding of how genes
encode for proteins is well developed, as are our techniques for
"transplanting" a gene from one organism to another.

What we have very little handle on is gene regulation. All those "non-coding"
genes that scientists used to think were junk? They are actually used to
control gene transcription.

Controlling this is infinitely easier in a simple organism like a hookworm,
but the complexities of in human borders on obscene.

------
samirahmed
Synthetic Biology is in great need for computational tools and expertise to
help advance the field.

Platforms like ClothoCAD are great places for those interested in open-source
software and syn-bio applications.

<http://www.clothocad.org/>

~~~
jostmey
Don't deceive yourself into thinking that you can program your way into
biological research. Biological research has very little to do with
apps/programming/web-development.

Synthetic biology requires an understanding of chemistry, molecular biology,
and genetic structure.

~~~
McGinness
DNA manipulation would be orders of magnitude more difficult and time
consuming with out computers as would anything involving chemistry, molecular
biology and understanding genetic structure.

Apps and programming/automation have everything to do with the future of the
field, its not just test tubes.

~~~
jostmey
True, but from what I've seen biologist for the most part can get along just
fine with only a basic knowledge of REGEX and spreadsheet software.

The biologist I've worked with tend to be a resourceful bunch, capable of
solving difficult problems with simple tools.

EDIT: Granted, there is a growing need for data-scientist who can help sort
through mountains of data for relevant information. But I don't think there is
much need for pre-built software solutions. Each lab faces unique problems,
and their software development needs, if any, are unique.

------
jostmey
How do they prevent the E. Chromi bacteria from eventually being displaced by
other non color coding poo bacteria? It seems to me that even if the E. Chromi
did work as advertised, that the bacteria would quickly (within days)
disappear from your intestinal track.

If anything, I would suspect that the E. Chromi would be at an evolutionary
disadvantage in the gut. This is because the E. Chromi would be expending
effort trying to color code poo, while their neighboring bacteria would just
be focused on digesting and reproduction. Based on the principles of
evolution, I would expect the E. Chromi bacteria to disappear entirely from
the gut with a few thousand generations of bacteria.

~~~
madhadron
Very important point. E. coli describes a range of organisms that share about
14% of their genome. For comparison, all of primates share over 99%. The
strains everyone uses for genetic engineering are derived from strains
isolated many decades ago and are incapable of colonizing hosts. They've also
been selected over the years to be hysterical (they over respond to any
stimulus, since when you're picking colonies to study response, you select the
bright, clear one...and if you do it again and again over the years, you
select for hysteria).

Poking around, I couldn't find the strain they used. They might have
engineered a gut isolate. They might not. Doesn't appear to say anywhere.

------
jergosh
Past participant of iGEM (International Genetically Engineered Machine, the
competition mentioned in the article) here. Infuriatingly, this writeup fails
to mention that the E. chromi (and all the other projects) was carried out by
undergraduate students (this is the team:
<http://2009.igem.org/Team:Cambridge/Team>), perhaps because it makes it sound
less trustworthy and sellable. According to the same website, the "designer
Daisy Ginsberg" was involved peripherally, at best.

------
madhadron
Others have already said this, but let's get it out in the open once and for
all:

Biochemistry has no relation to computation.

Neuroscience has no relation to computation.

Anatomy has no relation to computation.

Ecology has no relation to computation.

Someone using an computational image in any of these fields is trying to
impart a sense of familiarity for his audience. If you actually want to learn
any of these fields, you need to build your thought processes from scratch. No
part of you works like a computer.

------
corwinbad
Hi, My name is Omri and I'm the founder of Genome Compiler
(genomecompiler.com) - we built a free app for designing and ordering of
synthetic DNA - check it out!

also gave a talk at Google "solve for <X>":
<http://www.youtube.com/watch?v=F8qcDQaY8Mw> and at Leo Laporte Twit.tv:
<http://www.youtube.com/watch?v=BLhU1RGTHN4>

~~~
terangdom
Very cool idea! I think you should think carefully about the use cases.

Is it for someone who wants to take a gene from one organism, move it to
another and then order that organism? Is it for people wanting to manually
tweak genes to improve efficiency, slightly change function? What kinds of
manual tweaks? Is it for someone who wants to understand how an organism
works?

When /I/ look at it, I think it could benefit from being more abstract, but I
am not your target audience, so take this with a grain of salt. I don't think
looking at individual base pairs is useful. Amino acids might be, but are
still too emphasized in the interface. The most abstract view, showing genes
in order is not abstract enough. I want to see genes grouped by function (e.g.
reproductory system, energy production, acidity regulation etc). For each gene
I want to see:

a) High level description of function (already there, but in a single line
text field. Give more screen estate).

b) What activates the gene? i) Directly (e.g high concentration of Na+) ii)
Indirectly (e.g. genes a, b, c) iii) Very Indirectly (environmental stress)

c) As exact specification as possible of what happens when it is activated: i)
What does it activate in turn? ii) What does it catalyze?

------
gms7777
This may be nit-picking but in their diagram the color chart, portrayed
visually as a venn-diagram, is rather misleading. It seems to imply that if
you have colitis and worms, you have colorectal cancer. And if you have
everything, you're A-OK. Really, a color wheel would have been a far better
choice of diagram.

------
cdi
Make Anthrax/Bird Flu at home! Kill billions!

