Tag: DNA computation

Computational (DNA) storage – end of evolution part 4

Posted on by Ray in Storage density, Strategic Inflection Points

We were at a recent Storage Field Day (SFD26) where there was a presentation on DNA storage, a new SNIA technical affiliate. The talk there was on how far DNA storage has come and is capable of easily storing GB of data. But I was perusing PNAS archives the other day and ran across an interesting paper Parallel molecular computation on digital data stored in DNA, essentially DNA computational storage.

Computational storage are storage devices (SSDs or HDDs) with computational cores that can be devoted to outside compute activities. Recently, these devices have taken over much of the hyper-scalar grunt work of video/audio transcoding and data encryption activities which are both computationally and data intensive activities.

DNA strand storage and computers

The article above discusses the use of DNA “strand displacement” interactions as micro-code instructions to enable computation on DNA strand storage. The use of DNA strands for storage reduces the storage density of DNA information that currently use nucleotides to encode bits (theoretically, 2 bits per nucleotide) to 0.03 bits per nucleotide. But as DNA information density (using nucleotides) is some 6 orders of magnitude greater than current optical or magnetic storage, this shouldn’t be a concern.

A bit is represented by 5 to 7 nucleotides in DNA strand storage, which they called a domain, these are grouped into a 4 or 5 bit cells, with one or more cells arranged in a DNA strand register which is stored on a DNA plasmid.

They used a common DNA plasmid (M13mp18, 7.2k bases long) for their storage ring (which had many registers on it). M13mp18 is capable of storing several hundred bits, but for their research they used it to store 9 DNA strand registers.

The article discusses the (wet) chemical computational methods necessary to realize DNA strand registers and programing that uses that storage.

The problem with current DNA storage devices is that read out is destructive and time consuming. With current DNA storage, data has to be read out and then computation occurs electronically and then new DNA has to be re-synthesized with any results that need to be stored.

With a computational DNA strand storage device, all this could be done in a single test tube, with no need to do any work outside the test tube.

How DNA strand computer works

They figure shows a multi cell DNA strand register, with nic’s or mismatched nucleotides representing the value of 0 or 1. They use these strands, nic’s and toeholds (attachment points) on DNA strands to represent data. They attach magnetic beads to the DNA strands for manipulation.

DNA strand displacement interactions or the micro-code instructions they have defined include

  • Attachment, where an instruction can be used to attach a cell of information to a register strand.
  • Displacement, where an instruction can be used used to displace an information cell in a register strand.
  • Detachment, where an instruction can be used to a cell present in a register strand to be detach it from the register.

Instructions are introduced, one at a time, as separate DNA strands, into the test tube holding the DNA strand registers. DNA strand data can be replicated 1000s or millions of times in a test tube and the instructions could be replicated as well allowing them to operate on all the DNA strands in the tube.

Creating a SIMD (single instruction stream operating on multiple data elements) computational device based on strand DNA storage which they call SIMDDNA. Note: GPUs and CPUs with vector instructions are also SIMD devices

Using these microcoded DNA strand instructions and DNA strand register storage, they have implemented a bit counter and a Turing Rule 110, sort of like life, program. Turing Rule 110 is Turing Complete and as such, can, with enough time and memory, simulate any program calculation. Later in the a paper they discuss their implementation of a random access device where they go in and retrieve a piece of data and erase it.

Program for bit counting, information in solid blue boundary are the instructions and information in dotted boundary are the impacts to the strand data.

The process seems to flow as follows, they add magnetic beads to each register strand, add an instruction at a time to the test tube, wait for it to complete, wash out the waste products and then add another. When all instructions have been executed the DNA strand computation is done and if needed, can be read out (destructively). Or perhaps pass off to the next program for processing. An instruction can take anywhere from 2 to 10 minutes to complete (it’s early yet in the technology).

They also indicated that the instruction bath added to the test tube need not contain all the same instructions which means that it could create a MIMD (multi-instruction stream operations on multiple data elements) computational device.

The results of the DNA strand computations weren’t 100% accurate but they show that it’s 70-80% accurate at the moment. And when DNA data strands are re-used, for subsequent programs, their accuracy goes down.

There are other approaches to DNA computation and storage which we discuss in parts-1, -2 and -3 in our End of Evolution series. And if you want to learn more about current DNA storage please check out the SFD26 SNIA videos or listen to our GBoS podcast with Dr. J Metz.

Where does evolution fit in

Evolution seems to operate on mutation of DNA and natural selection, or selection of the fittest. Over time this allows good mutations to accumulate and bad mutations to die off.

There’s a mechanism in digital computing called ECC (error correcting codes) which, for example, add additional “guard” bits to every 64-128 bit word of data in a computer memory and using the guard bits, is able to detect 2 or more bit errors (mutations) and correct 1 or 2 bit errors.

If one were to create an ECC algorithm for human DNA strands, say encoding DNA guard bits in junk DNA and an ECC algorithm in a DNA (strand)computer, and inject this into a newborn, the algorithm could periodically check the accuracy of any DNA information in every cell of a human body, and correct it, if there were any mutations. Thus ending human evolution.

We seem a ways off from doing any of this but I could see something like ECC being applied to a computational DNA strand storage device in a matter years. And getting this sort of functionality into a human cell maybe a decade or two. Getting it to the point where it could do this over a lifetime maybe another decade after that.

Comments?

Photo Credit(s):

  • Section B from Figure 2 in the paper
  • Figure 1 from the paper
  • Section A from Figure 2 in the paper
  • Section C from Figure 2 in the paper
  • Section A from Figure 3 in the paper

Living forever – the end of evolution part-3

Posted on by Ray in Data consistency, Data integrity, Data precision, data protection, Data retention, Storage longevity, Storage reliability, Strategic Inflection Points

Read an article yesterday on researchers who had been studying various mammals and trying to determine the number of DNA mutations they accumulate at about the time they die. The researchers found that after about 800 mutations for mole rats, they die, see Nature article Somatic mutation rates scale with lifespan across mammals and Telegraph article reporting on the research, Mystery of why humans die around 80 may finally be solved.

Similarly, at around 3500 mutations humans die, at around 3000 mutations dogs die and at around 1500 mutations mice die. But the real interesting thing is that the DNA mutation rates and mammal lifespan are highly (negatively) correlated. That is higher mutation rates lead to mammals with shorter life spans.

C. Linear regression of somatic substitution burden (corrected for analysable genome size) on individual age for dog, human, mouse and naked mole-rat samples. Samples from the same individual are shown in the same colour. Regression was performed using mean mutation burdens per individual. Shaded areas indicate 95% confidence intervals of the regression line. A shows microscopic images of sample mammalian cels and the DNA strands examined and B shows the distribution of different types of DNA mutations (substitutions or indels [insertion/deletions of DNA]).

The Telegraph article seems to imply that at 800 mutations all mammals die. But the Nature Article clearly indicates that death is at different mutation counts for each different type of mammal.

Such research show one way on how to live forever. We have talked about similar topics in the distant past see …-the end of evolution part 1 & part 2

But in any case it turns out that one of the leading factors that explains the average age of a mammal at death is its DNA mutation rate. Again, mammals with lower DNA mutation rates live longer on average and mammals with higher DNA mutation rates live shorter lives on average.

Moral of the story

if you want to live longer reduce your DNA mutation rates.

c, Zero-intercept LME regression of somatic mutation rate on inverse lifespan (1/lifespan), presented on the scale of untransformed lifespan (x axis). For simplicity, the y axis shows mean mutation rates per species, although rates per crypt were used in the regression. The darker shaded area indicates 95% CI of the regression line, and the lighter shaded area marks a twofold deviation from the line. Point estimate and 95% CI of the regression slope (k), FVE and range of end-of-lifespan burden are indicated.

All astronauts are subject to significant forms of cosmic radiation which can’t help but accelerate DNA mutations. So one would have to say that the risk of being an astronaut is that you will die younger.

Moon and Martian colonists will also have the same problem. People traveling, living and working there will have an increased risk of dying young. And of course anyone that works around radiation has the same risk.

Note, the mutation counts/mutation rates, that seem to govern life span are averages. Some individuals have lower mutation rates than their species and some (no doubt) have higher rates. These should have shorter and longer lives on average, respectively.

Given this variability in DNA mutation rates, I would propose that space agencies use as one selection criteria, the astronauts/colonists DNA mutation rate. So that humans which have lower than average DNA mutation rates have a higher priority of being selected to become astronauts/extra-earth colonists. One could using this research and assaying astronauts as they come back to earth for their DNA mutation counts, could theoretically determine the impact to their average life span.

In addition, most life extension research is focused on rejuvenating cellular or organism functionality, mainly through the use of young blood, other select nutrients, stem cells that target specific organs, etc. For example, see MIT Scientists Say They’ve Invented a Treatment That Reverses Hearing Loss which involves taking human cells, transform them into stem cells (at a certain maturity) and injecting them into the ear drum.

Living forever

In prior posts on this topic (see parts 1 &2 linked above) we suggested that with DNA computation and DNA storage (see or listen rather, to our GBoS podcast with CTO of Catalog) now becoming viable, one could potentially come up with a DNA program that could

  • Store an individuals DNA using some very reliable and long lived coding fashion (inside a cell or external to the cell) and
  • Craft a DNA program that could periodically be activated (cellular crontab) to access the stored DNA for the individual(in the cell would be easiest) and use this copy to replace/correct any DNA mutation throughout an individuals cells.

And we would need a very reliable and correct copy of that person’s DNA (using SHA256 hashing, CRCs, ECC, Parity and every other way to insure the DNA as captured is stored correctly forever). And the earlier we obtained the DNA copy for an individual human, the better.

Also, we would need a copy of the program (and probably the DNA) to be present in every cell in a human for this to work effectively. .

However, if we could capture a good copy of a person’s DNA early in their life we could, perhaps, sometime later, incorporate DNA code/program into the individual to use this copy and sweep through a person’s body (at that point in time) and correct any mutations that have accumulated to date. Ultimately, one could schedule this activity to occur like an annual checkup.

So yeah, life extension research can continue along the lines they are going and you can have a bunch of point solutions for cellular/organism malfunction OR it can focus on correctly copying and storing DNA forever and creating a DNA program that can correct DNA defects in every individual cell, using the stored DNA.

End of evolution

Yes mammals and that means any human could live forever this way. But it would signify the start of the end of evolution for the human species. That is whenever we captured their DNA copy, from that point on evolution (by mutating DNA) of that individual and any offspring of that individual could no longer take place. And if enough humans do this, throughout their lifespan, it means the end of evolution for humanity as a species

This assumes that evolution (which is natural variation driven by genetic mutation & survival of the fittest) requires DNA variation (essentially mutation) to drive the species forward.

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So my guess, is either we can live forever and stagnate as a species OR live normal lifespans and evolve as a species into something better over time. I believe nature has made it’s choice.

The surprising thing is that we are at a point in humanities existence where we can conceive of doing away with this natural process – evolution, forever.

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