DNA Machine Language & Biological Computing

CS 301 Lecture, Dr. Lawlor

Consider, if you will, water.  Water is composed of molecules of hydrogen and oxygen.  A *lot* of molecules: one mole of water weighs about 18 grams (a little over one tablespoon), but contains 6.02 x 1023 water molecules.   (For comparison, the total count of all the bits on all the hard disks ever made comes to about 1022 bits.)

Water is also very fast.  Its molecular orientations change in around 50 femtoseconds (10-15 seconds, millionths of a nanosecond).  So in one second, while bouncing around each water molecule explores 2 x 1013 random orientations with the other molecules in its immediate neighborhood.  You can watch this sort of wriggling in any atomic-level simulation, like this biomolecule in super-slow-mo, or this potassium channel still billions of times slower than realtime!

So the molecules in one tablespoon of water are rated at 1.2 x 1037 orientations/second.  That's a ridiculous amount of potential computational horsepower, if we could figure out how to harness it!

Here's a good tour of various nano-scale sizes.

Mass (hydrogens)
Mass (Kg)
1 ... 200 Da
1.6 ... 300 × 10−27Kg
2 ... 6nm
10k ... 100k Da
1.6 ... 16 × 10−23 Kg
3.75 x 1012Da
6 x 10-15 Kg  (for 750MB of data!)
10 ... 100um
6 x 1014 Da
1 x 10-12 Kg

How to Harness It

Rather than compute with just plain water, biological systems use various interesting chemicals dissolved in the water.  Information is encoded in a long linear polymer called DNA, made of a sequence of Nucleotide "bases": adenine, guanine, cytosine, and thymine (which is switched to uracil in RNA).  In the "coding" region of DNA, these nucleotides A, G, C, and T/U are "expressed" into proteins, the giant molecules that get stuff done in your cells.  There are also long stretches of DNA that do not code for proteins; formerly called "junk DNA" because we didn't understand its function, these segments now appear to be crucial in determining how often a given stretch of DNA "executes" into a protein.  DNA is typically stored in an inactive, coiled-up orientation called a chromosome.

Amazingly, every known living entity uses the same basic coding scheme to get from DNA to proteins: the Universal Genetic Code.  The seqence of DNA that encodes a protein is composed of three-letter "codons", similar to machine code: each protein begins with an "ATG" sequence, and subsequent codons represent amino acids to be added to the protein, until the protein is ended with one of the three stop sequences, TAA, TAG, or TGA.  A typical protein forms from a chain of between one hundred and one thousand amino acids--similar to the length of many real functions in a computer program! 

Binary bits
Nucleotide bases
8-bit bytes of x86 machine code three-base codons in Universal Genetic Code
Stored on disk (stable version)
Stored in DNA (double-stranded helix)
Used from RAM (loaded copy)
Used from (m)RNA (single-stranded)
CPU: executes machine code in RAM
Ribosome: transcribes RNA to protein
One function
One protein
One program
One cell
Many programs working together
(parallel program)
One organism
Configuration file (written by installer)
Methylation sequence
Exit condition
Self-destruct sequence, like telomere

Not only does natural DNA work like a computer program, you can *build* a computational system using DNA, called "biological computing".  The advantage of biological computing is density--since the bits in your problem data be represented by a single molecule, and the computation proceeds in parallel and in 3D, you can search enormous search spaces quickly. 

For example, the human immune system fabricates antibodies, which have two sticky ends: both ends are designed to stick to a particular type of virus, bacteria, or parasite.  The middle of the antibody flags the pathogen for disposal by the immune system, and in the meantime the pathogens start sticking together due to the two sticky ends on the antibody.

Leonard Adleman demonstrated how to use DNA to quickly perform an exhaustive search in parallel.  The idea is to dump all the input molecules into a well-mixed test tube.  The inputs stick together in various ways, some of which represent the outputs you're looking for.  You then have to use chemistry to winnow out the (huge number of) incorrect outputs until you're left with the correct outputs, which you can read off.  Specifically, Adleman used the travelling salesman problem.  He represented each city with a short sequence of DNA, call the sequences A through  Z.  The routes between each each city were represented by a piece of DNA that will stick to ("bind") to one city and the next, where the length of the strand corresponds to the distance between the cities.  He then mixed all the cities and routes together, where they stuck together randomly.  Now, a solution to the salesman problem is encoded as a strand of cities and routes.  A solution has two features:
Other folks have recently built Turing machines with DNA, and "DNA nanofabrication" is a huge research field nowdays.

You can get companies online that will synthesize custom genes for you.  For example, $100 will buy you 10 nano-mols of flourescent probe molecules to tag a particular protein or sequence you're interested in.  1 mol is 6.022 x 1023 molecules.  So your 10 nano-mols is actually 6.022 x 1015 molecules.  That's 60 trillion molecules per dollar!  (For comparison, a $100 billion-transistor chip has just 10 million transistors per dollar.)

Biologically Inspired Computing

As components get smaller and faster, ordinary computers are getting more and more sensitive to small disturbances.  Already, cosmic rays can impact server uptimes. Anecdotally, there's a curious fact about space travel.  Due to the higher radiation:
Human brain cells can be killed in large absolute numbers by chemicals such as alcohol and a variety of viruses and bacteria (e.g., meningitis).  Yet the brain remains operational (at degraded efficiency) despite such abuse, and rarely suffers significant permanent damage from these injuries.  That is, the human brain is a suprisingly fault-tolerant computer.  Unfortunately, we have no idea how the human brain operates (see Gerstner's online neuron reverse-engineering attempts).  But we can infer that it's at least as smart as the reactions of a single cell.

Ecosystem Design

A single cell uses a number of interesting design principles.  Many of these same principles are shared by healthy ecosystems, economic markets, functioning democracies, and piles of gravel.  I've come to call these principles "ecosystem design":
As an example, I claim an automobile, CPU, dictatorship, and orderly stack of bricks use "machine design", not ecosystem design: these systems have crucial decisionmaker parts (e.g., the braking system, control unit, dictator, or middle brick) whose failure can dramatically change the entire system.   Machine design requires somebody to go in and fix these crucial parts now and then, which is painful.

All modern programming languages encourage machine-style design (for example, what happens to a for loop if the variable "i" freaks out?).  At the moment, nobody knows what an ecosystem-design language would look like!