The most amazing science paper you can read this year! Synthetic embryos grown ex-utero (no sperm/no eggs/no utero needed) - the scientific basis for renewal.bio
Using Twist Bioscience DNA - interesting data points:
215Pb/Gram
~1,300 copies per unique oligo enough to get a 100% data back
Almost unlimited coping of recoverable data using PCR
Now only need to increase the throughput and price of DNA synthesis by 4-6 orders of magnitude
What possibilities are opened up when 215Pb/Gram with good I/O and price is reality?
With computing power increasing 1 order of magnitude around every 5 years (Moore's law), this might be reality by 2027.
An antecedental story is computer graphics, it only took 20 years for to go from idea to reality. Learned a lot listening to a talk at work by Alvy Ray Smith a couple years back. The true poineers are building now not for what is possible now but for what will be possible tomorrow. This article gives some context https://www.forbes.com/asap/2001/0528/052.html
> What possibilities are opened up when 215Pb/Gram with good I/O and price is reality?
The data storage is almost totally irrelevant. When you improve DNA synthesis by 3-4 orders of magnitude, you make it dirt-cheap to synthesize whole custom genomes, hyper-optimized for anything you wish. (Currently, the state of the art is synthesizing an E coli genome takes multiple years and a large international collaboration.) CRISPR only lets you do a few edits at a time at most, in some parts of the genome; imagine being able to do tens of thousands of edits as easily as 1 edit. At that point, you're hardly even 'editing', you're designing organisms as a whole. The Church lab has some astounding proposals for things you can do when you are able to synthesize a whole genome, like cleaning out all the retrovirals, movable elements, recoding the genome for total viral immunity, on top of the obvious stuff like eliminating all mutation load or increasing specific traits by dozens or hundreds of standard deviations. The mind boggles.
Craig Venter, Clyde Hutchison and Daniel Gibson produced a minimal genome in a relatively short period of time and even transplanted it. This was a "bottom up" approach in which all of the DNA was synthetic. This is a trivial thing for this team now. As you mentioned, when synthesis costs drop dramatically, things will get interesting!
Another viewpoint is that in an academic setting, there is no reality-check, professors rarely loose their jobs, students are free, and operating budgets are small enough to be overlooked. The only people judging are your peers, who often have the same kind of nonsense scheme. Even if it doesn't work, and is completely useless, the idea of DNA storage is guaranteed to never die.
Are you sure you understand the concept AND the limitations of PCR? I predict: No.
There are many forms of DNA. Single stranded, double stranded, circular etc. etc.
I assume we were talking about non-circular DNA. ds/ss does not matter, for PCR you would have to go ds anyway. You realize that strand shortening would be a problem? I could think about ways to correct this but it is not trivial.
This is Omri (founder of Genomecompiler.com). I'm always amazed about how many biologists think their work is pipetting small amounts of liquids and performing massively low productivity experiments rather then their real work of increasing our understanding of nature and finding solution to real world problems (like disease, hunger, aging, running out of civilization critical commodities, etc) using the best available tools.
Robots aren't taking our jobs - they help us be more productive so a biologist Ph.D. might in the future get paid like a CS undergrad!
Hehe funny that you mention phiX174 in the context of programming, that virus is amazing... Part of the reason phiX174 is so small is that it is "compressed" by having overlapping genes; in one area, three genes overlap in the same place! This is possible because there are 6 valid reading frames (direction and start point) for reading DNA: {forward or backward} x {address % 3 == 0, 1, or 2}.
In college I actually got to take part in refactoring that virus' genome into a decompressed version with no gene overlaps. And it worked! The decompressed version is still a functioning phage, and since there are no longer gene overlaps, future genetic engineers will have a much easier time modifying the phage as they see fit.
I have no doubt that viruses of the computer kind also have made use of such techniques; and overlapping for obfuscation, not size-optimisation, is also a commonly seen trick in malware.
Hm, I used to work for Clyde Hutchison (and Ham Smith)... They told me that it didn't work when they made a naive decompression. Was there something they missed?
Did their naive decompression make the genome longer? If so, it probably didn't fit in the capsid. In our version, we had to provide one of the genes (gene F) in a plasmid in the host cell, in order to reduce the length of the decompressed genome to fit inside the capsid. See this section of our paper:
[The naive] decompression added 909 nucleotides to the wild-type genome. We next addressed practical constraints arising from the length of DNA that can be physically packaged within a øX174 capsid without impacts to reproductive fitness. Previous work has shown that the length of a øX174 genome, when packaged in vitro, must be kept within a few percent of the 5386 nucleotide wild-type length in order to avoid any significant fitness decrease ( Aoyama and Hayashi, 1985). Similar results were shown in vivo ( Russell and Muller, 1984). To reduce the decompressed genome length we removed the first 916 nucleotides of gene F, encoding the coat protein ( Air et al., 1978). We chose gene F because a plasmid containing a restriction fragment encoding wild-type gene F was able to complement two conditional gene F mutations ( Avoort et al., 1983). Additionally, the gene F coding sequence is greater than the total of the combined increases needed to implement the øX174.1 genome design. The truncated gene F version of the decompressed genome was named øX174.1f. To complement øX174.1f when transformed into host cells we designed a medium copy vector expressing gene F under control of a rhamnose-inducible promoter ( Fig. S1).
That's pretty amazing. I'm guessing DNA compactness is a survival advantage for viruses, and that's how this emerged? Is gene overlap common in other species?
Gene overlap is extremely rare actually! When phiX174 was first discovered, some researchers wondered if such a complexly intertwined system could even have evolved naturally, or if it might suggest that the virus was hand-engineered: http://adsabs.harvard.edu/abs/1979Icar...38..148Y
