1. DNA Computing Computation with the Code of Life Michael Ang <m@michaelang.com> Interactive Telecommunications Program New York University February 16, 2007

2. What is it? Invented by Len Adleman (1994) Invented by Len Adleman (1994) Realized combinatorial properties of DNA could be used to solve problems encoded as strings of DNA Realized combinatorial properties of DNA could be used to solve problems encoded as strings of DNA

3. Why is it interesting? Cross-discipline (CS meets Molecular Biology) Cross-discipline (CS meets Molecular Biology) High data density High data density Data and computation happens at molecular level Data and computation happens at molecular level Each base of DNA is 0.35nm Each base of DNA is 0.35nm Massively parallel Massively parallel 10 12 or more copies of DNA in a test tube 10 12 or more copies of DNA in a test tube Use biological enzymes to make these copies Use biological enzymes to make these copies Energy efficient Energy efficient Potential to perform computation inside the body Potential to perform computation inside the body Though big challenges before a reality Though big challenges before a reality

4. What is DNA? Source code to life Source code to life Instructions for building and regulating cells Instructions for building and regulating cells Data store for genetic inheritance Data store for genetic inheritance Cellular machinery (enzymes) translates DNA into proteins, duplicates, repairs, etc. Cellular machinery (enzymes) translates DNA into proteins, duplicates, repairs, etc. Think of enzymes as hardware, DNA as software Think of enzymes as hardware, DNA as software

5. What is DNA made of? Composed of four nucleotides (+ sugar- phosphate backbone) Composed of four nucleotides (+ sugar- phosphate backbone) A – Adenine A – Adenine T –Thymine T –Thymine C – Cytosine C – Cytosine G – Guanine G – Guanine Bond in pairs Bond in pairs A – T A – T C – G C – G

6. How does it work? Use specially coded DNA as initial conditions for biological reaction Use specially coded DNA as initial conditions for biological reaction Natural enzymes duplicate DNA Natural enzymes duplicate DNA Matching DNA base pairs attach to each other Matching DNA base pairs attach to each other Find answer in resulting soup of DNA strands Find answer in resulting soup of DNA strands

7. Travelling Salesman Simple problem (at small scale) Simple problem (at small scale) Complexity scales exponentially Complexity scales exponentially

8. Algorithm  Generate all possible routes  Select routes that start with the initial city and end with the destination city  Select itineraries with the correct number of cities  Select itineraries that contain each city once

9. Algorithm  Generate all possible routes  Select routes that start with the initial city and end with the destination city  Select itineraries with the correct number of cities  Select itineraries that contain each city once

10. City Encoding

11. Annealing Use “a lot” (10 13 ) copies of each city and path Use “a lot” (10 13 ) copies of each city and path

12. We’ve made all the routes

13. Algorithm  Generate all possible routes  Select routes that start with the initial city and end with the destination city  Select itineraries with the correct number of cities  Select itineraries that contain each city once

14. Polymerase Chain Reaction

15. And repeat…

16. Algorithm  Generate all possible routes  Select routes that start with the initial city and end with the destination city  Select itineraries with the correct number of cities  Select itineraries that contain each city once

17. Gel electrophoresis “Race” the DNA through a gel “Race” the DNA through a gel Shorter lengths go faster Shorter lengths go faster

18. Algorithm  Generate all possible routes  Select routes that start with the initial city and end with the destination city  Select itineraries with the correct number of cities  Select itineraries that contain each city once

19. Affinity purify Pull out strands matching one city at a time Pull out strands matching one city at a time

20. We have our answer Sequence result or perform more PCR reactions to determine combinatorically Sequence result or perform more PCR reactions to determine combinatorically Took Adleman 7 days to run through the steps Took Adleman 7 days to run through the steps Actual “computation” took minutes Actual “computation” took minutes

21. Problems/Challenges Relatively high error rate in DNA Relatively high error rate in DNA Sometimes bases don’t align properly Sometimes bases don’t align properly Problem complexity still scales exponentially Problem complexity still scales exponentially 200 city problem might take DNA weighing more than Earth 200 city problem might take DNA weighing more than Earth Many people doubtful… Many people doubtful…

22. Can I do it? If you have access to a lab, yes If you have access to a lab, yes DIY seems possible ( <$500 ) DIY seems possible ( <$500 ) Personal Biocomputing Personal Biocomputing – Eugene Thacker

23. Further Research Use to break DES (1995) Use to break DES (1995) Turing Machine (at least… “similar to”) (2001) Turing Machine (at least… “similar to”) (2001) Play tic-tac-toe (2003) Play tic-tac-toe (2003) DNA computer to detect and treat cancer (2004) DNA computer to detect and treat cancer (2004) Use enzymes and DNA to create state machine using mRNA as input Use enzymes and DNA to create state machine using mRNA as input Output DNA sequence to suppress disease causing gene Output DNA sequence to suppress disease causing gene In vitro (petri dish) so far In vitro (petri dish) so far Much harder in vivo (living cell) Much harder in vivo (living cell)

24. Maya II – Tic Tac Toe

25. Maya II – Logic Gates

26. Maya II – Fluorescent Output

27. DNA Automata

28. 10 12 automata run independently and in parallel on potentially distinct inputs in 120  l at room temperature at combined rate of 10 9 transitions per second with accuracy greater than 99.8% per transition, consuming less than 10 -10 Watt. A nanoscale programmable computing machine with input, output, software and hardware made of biomolecules Nature 414, 430-434 (2001)

29. (Video from Weizmann Institute)Video from Weizmann Institute

30. So what? Computation at molecular level Computation at molecular level Computation (potentially) within cells Computation (potentially) within cells Operate with cellular messages as input and output Operate with cellular messages as input and output Operate near theoretical power limits Operate near theoretical power limits Computer Science implemented in Biology Computer Science implemented in Biology Practical applications still a dream… Practical applications still a dream…

31. To correctly gauge the practicality of molecular computing will require inputs from experts in a wide variety of fields including: biology, chemistry, computer science, engineering, mathematics and physics. - Len Adleman (1995)

32. References “What is DNA” - Genetics Home Reference “What is DNA” - Genetics Home ReferenceWhat is DNAWhat is DNA “DNA Computer Could Target Cancer” – Nanotech Web “DNA Computer Could Target Cancer” – Nanotech WebDNA Computer Could Target CancerDNA Computer Could Target Cancer “DNA Computing: A Primer” – Arstechnica “DNA Computing: A Primer” – ArstechnicaDNA Computing: A PrimerDNA Computing: A Primer “On Constructing a Molecular Computer” – Len Adleman “On Constructing a Molecular Computer” – Len AdlemanOn Constructing a Molecular ComputerOn Constructing a Molecular Computer “Breaking DES using a molecular computer” - D. Boneh, C. Dunworth, and R. Lipton “Breaking DES using a molecular computer” - D. Boneh, C. Dunworth, and R. LiptonBreaking DES using a molecular computerBreaking DES using a molecular computer “Injectable Medibots: Programmable DNA could diagnose and treat cancer” - Alexandra Goho “Injectable Medibots: Programmable DNA could diagnose and treat cancer” - Alexandra GohoInjectable Medibots: Programmable DNA could diagnose and treat cancerInjectable Medibots: Programmable DNA could diagnose and treat cancer “First game-playing DNA computer revealed” – New Scientist “First game-playing DNA computer revealed” – New ScientistFirst game-playing DNA computer revealedFirst game-playing DNA computer revealed “ “Programmable and autonomous computing machine made of biomolecules” - Benenson, Paz-Elizur, Adar, Keinan, Livneh & ShapiroProgrammable and autonomous computing machine made of biomolecules “Personal Biocomputing” – Eugene ThackerPersonal Biocomputing “Biological Nanocomputer” – Weizman InstituteBiological Nanocomputer “Computer Made from DNA and Enzymes” – National Geographic NewsComputer Made from DNA and Enzymes

33. Thanks Michael Ang <m@michaelang.com> Interactive Telecommunications Program New York University February 16, 2007