Safety for the environment is probably implicit here as well, but the focus should be on the people who may come in contact with large amounts of synthetic DNA used to encode information as a data storage medium.

The idea of using DNA as a digital storage medium is not new. Two papers are listed below but there are many others.

Recently the concept has been further highlighted by the news of a "movie" being encoded using CRISPR-Cas. A Harvard University video explains the process:

In this video, Wyss Institute and Harvard Medical School researchers George Church and Seth Shipman explain how they engineered a new CRISPR system-based technology that enables the chronological recording of digital information, like that representing still and moving images, in living bacteria. Credit: Wyss Institute at Harvard University

For more information, please visit: https://wyss.harvard.edu/taking-cells...

below: a GIF showing the original data, and the "movie" interpreted from the recording in DNA. From the Los Angeles Times:

enter image description here

DNA DVR? Scientists have uploaded a short movie of a galloping horse into the DNA of living bacteria and were able to retrieve it with a 90% success rate. (Seth Shipman)

The immediate application in the Harvard Wyss Institute work seems to be (based on my understanding of the video) in-situ data logging, where information relevant to an experiment is recorded in the DNA of cells involved in the experiment. So the use of a moving image is a way to bring home the key point of "chronological recording of digital information".

Other uses involve the DNA itself, stored outside of living cells, as simply a mass storage medium.

QUESTION: I'm wondering if there are sequences that are likely to become algorithmically avoided as standard practice for safety reasons (or should be) when using DNA as a digital storage medium. The DNA may be handled by IT personnel rather than trained biologists, or shipped, or otherwise not be treated with the same diligence to safety that synthetic DNA is handled by researchers today.

Some other discussions of DNA as a storage medium:

Next-Generation Digital Information Storage in DNA, Church, Gao, Kosari, 2012. doi: 10.1126/science.1226355

Towards practical, high-capacity, low-maintenance information storage in synthesized DNA, Goldman et al. 2013. doi:10.1038/nature11875

For further background on the temporally encoded data work, see the excellent answers to the question What does it mean to “write an image and GIF into the DNA of bacteria”?

edit: I'll quote a comment here just to make sure that the word safety isn't misinterpreted as data integrity or the safety of the bacteria:

When speaking of safety issues related to the handling of biological or biomolecular samples, it's the safety of people that we worry about. Safety rules, safety procedures, safety courses, safety glasses, these are for the safety of the human, not the safety of the sample.

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    $\begingroup$ An identical or near-identical question to this has been posted before, but I can't find it, maybe it was deleted. Just a reminder in case anyone else can find it... $\endgroup$ – Bryan Krause Jul 12 '17 at 21:49
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    $\begingroup$ @BryanKrause I seem to remember that there is one sentence in this one five year old paper. The field of molecular biology moves quickly, so that doesn't make it the last word on the subject going forward. Is there something about this question you find unsettling? Can you let it go for a day or two and see if some informative answers are posted? Possibly post one yourself? Stackexchange is about getting answers for ones self, but also the generation of answers that can be read by many. $\endgroup$ – uhoh Jul 12 '17 at 22:24
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    $\begingroup$ I'll try to write an answer when I have more time, but the two answers here are examples of why I was asking you about Church. Neither of the writers of these answers seem to have read Church, because they are ignoring all of the issues that paper raises. If you included that information in your question and made clear what about those issues you are interested in, you would get better quality answers. $\endgroup$ – Bryan Krause Jul 13 '17 at 23:06
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    $\begingroup$ You might br interested in this $\endgroup$ – another 'Homo sapien' Jul 16 '17 at 8:08
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    $\begingroup$ @another'Homosapien' Lots of goodies to read there - I'll add a reference to that in my question. Thanks!! $\endgroup$ – uhoh Jul 16 '17 at 9:03

Yes, there could be sequences that a DNA based system could not store handle/very well: repetitive DNA sequences.

Not only do such sequences make a lot of problems during the sequencing ('reading of data'), but they are also more prone to form secondary structure elements like loops, since repetitive DNA can bind to itself in various different ways. This means that similar to natural occuring repeats they are more likely to mutate during DNA amplicifation (the number of 'copies' can quite easily change), which makes the 'data' more instable.

A possible way to solve this problem would be to use specialised data formats that avoid as much Repetition of data as possible (similar to how zip or jpg files work)

Otherwise I agree with Nathan, that DNA by itself is not dangerous (since it won't do anything outside of cells, and the bacteria used in molecular biology are generally harmless unless you start eating them in large quantities or otherwise getting them in your body). The possibility that the DNA could somehow code for toxic proteins is very very low, and you could just check that the 'data' in the DNA does not form a protein by chance anyway.

  • $\begingroup$ Have you read the discussion of safety issues in the paper the OP cites? This answer suggests you haven't. Biology.SE prefers researched and cited answers. Although you have a couple links in your answer, neither are directly related to the issue at hand. $\endgroup$ – Bryan Krause Jul 13 '17 at 23:07
  • $\begingroup$ Thanks for taking the time to post. You've actually answered an interesting question that I didn't ask but wish I did! I've asked about safety and you've discussed data integrity or stability, which is probably a more interesting topic. $\endgroup$ – uhoh Jul 14 '17 at 4:13
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    $\begingroup$ Given the quantity of storage, with no avoidance system, you will eventually encode toxic or dangerous proteins. But the system would have no molecular machinery to even transcribe it into proteins, let alone what may be necessary for proper secondary processing so that the protein would be active. Now if they started somehow storing data into proteins as a final form, we'd have to be a lot more careful. $\endgroup$ – Nathan Jul 14 '17 at 13:46
  • $\begingroup$ Data written on a discarded floppy disk (remember those?) or hard drive or thumb drive in a landfill has no hope of its data getting into the bacteria in the landfill, but the fate of data stored in DNA is less certain. In DNA written without safety rules, there may be sequences that bacteria or phages could find not necessarily toxic, but instead "very interesting" or even helpful. That's one random scenario. $\endgroup$ – uhoh Jul 14 '17 at 15:17

Even if DNA drives (to give it a name) are being handled by IT professionals instead of trained biologists, we can still expect the environment to be clean enough so that no organism would tend to be affected by it. Also, as @nathan points out in the other answer, free DNA cannot do anything on its own. Its just like an open book, you can't get anything from it unless you have a reader (protein) for it. There have been no reports claiming that foriegn DNA (called cell-free DNA or cf-DNA for humans) has ever caused any health issues. In fact, there are no reports of cf-DNA even being transcribed by humans. You might also want to have a look at this to find out more. However, as pointed out by @AlanBoyd in comments, organisms residing inside humans can take up free floating DNA from their surroundings. For example, Heliobacter pylori has been shown by Stingl et al, 2009 to take up free DNA from its surroundings. Keeping that in mind, there are chances that DNA drives could be harmful (if, by chance, the drive contains some genes that might provide some antibiotic resistance to the pathogen). Some microbes show a phenomenon known as natural competence i.e. they simply take up plasmid DNA from their environment, break it into parts by restriction enzymes and add it into their genome. These organisms, which generally possess sex pilli for DNA take up, can be a major threat to the use of DNA drive if the users of DNA drives show carelesness while handling and mainpulating DNA since some of this DNA might provide them with antibiotic resistance or capability to infect humans. However, we can prevent this from happening by making sure there are no restriction enzyme recognition sites in the DNA of the drive, so that the organism cannot cut the DNA for ligation into its own genome.

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    $\begingroup$ This looks like the beginning of a fascinating answer! As I mentioned in this comment (and obliquely in this comment) sequences that might be avoided for data integrity might be a more interesting question, but I've asked about safety. Maybe you can divide these various items into data integrity and safety categories or somehow make it clear which would need to be avoided for reasons of safety? $\endgroup$ – uhoh Jul 16 '17 at 13:17
  • $\begingroup$ @another'Homosapien' my understanding of the question is that DNA sequences created solely for data storage might inadvertently contain elements that are biologically unsafe - is this so, and what precautions would need to be taken to avoid this? $\endgroup$ – Alan Boyd Jul 16 '17 at 13:30
  • $\begingroup$ When talking about safety issues related to the handling of biological or biomolecular samples, it's the safety of the person that we worry about. Safety rules, safety procedures, safety courses, safety glasses, these are for the safety of the human, not the safety of the sample. There may be a bias that DNA is "safe" so the word must be talking about something else, and of course data integrity is more interesting and easier to answer. I can clone this question and re-ask specifically about safety, and change this one to data-integrity if it works with all the answers here, what do you think? $\endgroup$ – uhoh Jul 16 '17 at 13:32
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    $\begingroup$ 'none of the organisms that I know tend to just take up free DNA from their environment' many bacteria do this such as Helicobacter - see this paper for example $\endgroup$ – Alan Boyd Jul 16 '17 at 13:55
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    $\begingroup$ Comments are not for extended discussion; this conversation has been moved to chat. $\endgroup$ – WYSIWYG Jul 18 '17 at 14:01

I would say no for two reasons.

The first is I don't know of any DNA sequences that are in themselves infectious. You'd need the proper cellular machinery to make anything out of them. If I'm not mistaken even most prokaryotes have varied defenses against random pieces of DNA getting incorporated into their systems. Otherwise they'd never have stable cores. Viruses and bacteria etc have to use strategies to get around those defense systems.

The second reason, even if I'm wrong on the first, is that this system must be designed to be as free as possible from outside influence. A system designed to minimize external influence also inherently minimizes influence to the outside, at least in this case.

This wouldn't be handled by IT people unless it was somehow massively automated. Again no clue on the final form, so hard to say.

  • $\begingroup$ Have you read the discussion of safety issues in the paper the OP cites? This answer suggests you haven't. Biology.SE prefers researched and cited answers. $\endgroup$ – Bryan Krause Jul 13 '17 at 23:07
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    $\begingroup$ Thanks for your thoughts. Infectious proteins took science by complete surprise decades ago, and it took a while for people to agree it was happening. However, as you point out, since DNA is primarily information, it probably doesn't have much ability to induce molecular changes on its own. Instead, it usually needs to be accepted into, or forced into a transcripting environment. $\endgroup$ – uhoh Jul 14 '17 at 4:29
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    $\begingroup$ @uhoh Exactly. If you've never tried to transfect e. coli in a lab, I can tell you that it is nontrivial, at least for an undergrad who only does it a couple of times. I wasn't able to access the Nature paper so if there is a list of other safety concerns I did not consider, my apologies. Infection was just the first thing that popped into my mind as far as safety. I guess other than that I would think all the other safety issues would be related to standard DNA sequencing work, which is pretty well OSHA'd up. $\endgroup$ – Nathan Jul 14 '17 at 13:42

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