1. Beyond Silicon: Tackling the Unsolvable with DNA

2. What is a DNA Computer? Stores information using sequences of the four nucleic acids that comprise the DNA: A, T, C, G. Does calculation via Chemical reactions are the actual calculation DNA melting and annealing, etc. and, Lab procedures narrow down the answers: extraction, amplification, etc.

3. How does it work? Example: The first DNA computer. Creator: Leonard Adleman, USC, 1994 The problem he solved with DNA: Hamiltonian Path Problem with 7 nodes

4. How does it work? Hamiltonian Path Problem Definition of the question” In a Graph (connected), is there a path from a given starting vertex to a given ending vertex that visits all the vertices in the graph once and only once. The problem is NP-complete: With any existing algorithm, even a computer that runs at 1 trillion operations per second takes too long to solve the problem with 50 nodes.

5. How does it work? Adleman’s protocol: 1. Create unique 20-nucleotide sequences to represent vertices. Create edges like this: V1: ATT|CGG V2: TAG|ACT E(V1, V2): GCC|ATC 2. Throw many copies of vertex and edge sequences in the same solution. “Cap off” the beginning and ending nodes. Paths will form. Add ligase to fix gaps. AGTCCA……ATTCGG{}TAGACT……GTACTC TCA………………GCCATC ……………… GAG

6. How does it work? Adleman’s protocol: 3. Amplify with polymerase chain reaction (PCR) to extract the double-stranded DNA sequences starting with the V_start sequence and ending with the V_end sequence. 4. Run a gel electrophoresis on the results of Step 3 to separate out the DNA strands that are 140-nucleotide long.

7. How does it work? Adleman’s protocol: 5. Melt the resulting solution from Step 4 down to single- stranded DNA. Use the magnetic bead technique to extract the sequences that contain all 7 vertices. 6. Detect if there are any DNA sequences in the remaining solution with PCR and gel electrophoresis.

8. How does it work? Models of Computation: Adleman’s: Generate and Test Brute-force DNA material required is exponential to the number of vertices in the graph. Programmed Chain Reaction: controls a cascade of chain reactions that results in the answer to a desired computation. Guarnieri et al. (1996) implemented this model to add two non- negative binary numbers through a chain reaction The amount of DNA material required by their design is linear to the number of bits

9. Pros and Cons Disadvantages: Slow lab procedure Can’t compare to conventional computers in terms of operations per unit of time Low usability Pretty interfaces seem remote and inconceivable. It is easier to to arithmetic with a regular calculator. Material involved is unstable DNA can hydrolyze in water after a long time Random experimental failures.

10. Pros and Cons Advantages: Massive Parallelism Outweighs the disadvantage of slow unit speed. Information Density 1 liter of water holds 10 20 molecules, enabling massive parallelism Energy efficiency Some reactions generate energy

11. Pros and Cons Advantages: Massive Parallelism and Information Density Can solve problems that conventional computers can’t solve in a reasonable amount of time. NP problems Cryptography : Boneh et al (1995) describe an algorithm for breaking the Data Encryption Standard (DES); Can break <=57-bit key DES in 4 months with reasonable amount of resources and perfect operations

12. Pros and Cons Advantages: Energy Efficiency Self-sufficient systems are possible. Researchers at Weizmann Institute of Science in Israel devised a molecular computer that ran at over 100,000 times the speed of the fastest existing PC. In this new device, energy is released as the enzyme FokI breaks bonds in the DNA double helix, providing energy for the system.

13. Conclusion DNA computers have the potential to solve problems that can’t be solved by conventional computers, though they are still in early development stages. Combining the technology of the two will be meaningful.