Technology and the future of medicine

1. Technology and the future of medicine The promise and perils of nanotechnology Michael T. Woodside National Institute for Nanotechnology and Department of Physics

2. Outline 1. Introduction, definitions, background 2. Promise and peril at the level of science fiction and hype/doom 3. Constraints on the vision imposed by scientific realities 4. Specific examples of promising, realistic, near-term nanotechnology applications: computation with quantum-dot cellular automata single-molecule tests for drug discovery 4. Specific examples of realistic, near-term concerns with nanotechnology

3. What is “nanotechnology”? Many possible definitions “Nanoscience is the study of phenomena and manipulation of materials at atomic, molecular and macromolecular scales, where properties differ significantly from those at a larger scale.” “Nanotechnologies are the design, characterisation, production and application of structures, devices and systems by controlling shape and size at nanometre scale.” Royal Society (2004) Nanoscience and nanotechnologies: opportunities and uncertainties http://www.nanotec.org.uk/finalReport.htm Drexler-Merkle differential gear (model), 1995

4. Richard Feynman: “There’s plenty of room at the bottom” Address to American Physical Society, 1959: I would like to describe a field, in which little has been done, but in which an enormous amount can be done in principle. This field is not quite the same as the others in that it will not tell us much of fundamental physics (in the sense of, "What are the strange particles?") but it is more like solid-state physics in the sense that it might tell us much of great interest about the strange phenomena that occur in complex situations. Furthermore, a point that is most important is that it would have an enormous number of technical applications. What I want to talk about is the problem of manipulating and controlling things on a small scale. I will not now discuss how we are going to do it, but only what is possible in principle – in other words, what is possible according to the laws of physics. I am not inventing anti-gravity, which is possible someday only if the laws are not what we think. I am telling you what could be done if the laws are what we think; we are not doing it simply because we haven't yet gotten around to it. How do we write small? Information on a small scale The marvelous biological system Problems of lubrication and waste heat Rearranging atoms …

5. Popularisation: Eric Drexler Inspired by Feynman, molecular biology Influenced by ideas of “limits to growth” in a finite world Controversial reception in scientific community Drexler-Smalley debates 2001-2003 Impact on public perception 1986

6. Nanotechnology: Promise Many possibilities have been conceived: • New materials with enhanced properties: strength, durability, functionality,… invisibility cloak diamandoid carbon nanotube space elevator coloured nanoparticles

7. Nanotechnology: Promise Many possibilities have been conceived: Quantum computers Smartdust Assemblers wirelessly networked nanosensors Assemble anything from atomic constituents Combination with AI: swarm of intelligent computation Use “quantum wierdness” to solve intractable problems “molecular nanotechnology” Also energy storage, transmission, ...

8. Nanotechnology: Promise Many possibilities have been conceived: Medical “nanobots” • Drug delivery • Distributed sensing and real-time monitoring • Enhanced physical capabilities: strength, • endurance, … • Enhanced immune system • Cure diseases in real-time • Interface with neurons: expand • mental capabilities Combine with AI and synthetic biology • Cellular repair • Longevity

9. The motivation for molecular nanotechnology 1. Biology provides proof of the feasibility of nanotechnology, supplies a fully functional model 2. Structures that are able to self-replicate exist in Nature 3. Nanoscale machines do not violate any laws of physics, in principle 4. We can conceive of “bottom-up” fabrication, even starting from the atomic level 5. Structures where atoms are arranged precisely exist in Nature Hence we should be able to build nanoscale, self-replicating, programmable “assemblers” capable of manufacturing arbitrary objects from atomic constituents

10. The basic concept Molecular nanotechnology: “Thorough, inexpensive control of the structure of matter based on molecule-by-molecule control of products and byproducts of molecular manufacturing.” Unbounding the Future, Drexler et al., 1991 Based on: The concept of the molecular “assembler”: pick up and manipulate atoms, establish chemical bonds between arbitrary atoms Incorporation of assemblers into self-replicating machines Molecular-scale computation, programming, data storage, and integration

11. The Promise of Molecular Nanotechnology “Imagine a manufacturing technology capable of making trillions of tiny machines — each the size of a bacteria. Each machine could contain an onboard device programmed to control a set of molecular scale tools and manipulators. An individual machine could be designed to manufacture superior materials, convert solar energy to electricity, or even, ultimately, enter the body to fight disease and aging at the cellular and molecular level. Materials hundreds of times better than today’s best materials, vastly more powerful computers, precise machinery that doesn’t wear out, and a revolution in clean manufacturing are but a few of the predicted benefits of applying these new machines.” source: Zyvex home page www.zyvexlabs.com/Publications2010/WhitePapers/MolecularNanotech.html …but many potential dangers lurk!

12. Nanotechnology: Perils Again, many possibilities have been conceived: New toxic materials, easily spread and hard to contain competition from ETC group Tiny, invisible weapons Weapons control impossible: hard to embargo, hard to verify Self-replicating weapons “GI Joe” (2009)

13. Nanotechnology: Perils More insidious dangers: Undetectable and pervasive surveillance: totalitarian nightmare Neural interfaces: thought control/possession Medical nanobots: remote control of health Consequences of system crashes in enhanced bodies and minds Change in the economic basis of society

14. Nanotechnology: Perils Higher-level dangers: Societal fragility: consequences of network crashes in complex systems run by pervasive smartdust mesh Emergent complexity Swarm intelligence 2002 2000

15. Nanotechnology: Perils Ultimate nightmare scenarios: Self-replication of assemblers, “grey goo” Self-replicating disassemblers

16. (Un)Fortunately reality intrudes… No obvious way forward for many of the dreams Simple example: carbon nanotubes as ideal electrical nanowire • 1 nm wide • up to mm long • very low electrical • resistance • can be metal or • semiconductor Carbon-based electronics! But: 15 years on, still can’t grow them to order—so how can they form the basis of a technology to replace Si (purity of 99.9999999% is routine)?

17. (Un)Fortunately reality intrudes… No obvious way forward for many of the dreams Simple example: carbon nanotubes (CNT) as ideal electrical nanowire Suppose we could make CNTs to order… …circuits would be 10,000- 1,000,000 denser! • How do we connect to the • outside (“macro”) world? Practical problems that are “just engineering”… but are very hard and have no obvious solution! • How do we check that it’s • built properly? fault-tolerant architectures…

18. (Un)Fortunately reality intrudes… More basically: flawed philosophical premise for molecular nanotechnology Is it even possible to build today anything that we can conceive, provided it does not violate physical laws? NO And it never has been! Consider dream of human-powered flight: First human-powered flight, 1977 400 years later Leonardo’s ornithopter, 1485

19. The laws of physics must still be respected Issues ranging from the mundane to the fundamental: • Heat dissipation: as physical size decreases and density of components • increases, waste heat becomes a problem just as in computers today • Friction: as parts scale down to near-atomic dimensions, what acts as • a lubricant? How do we control inter-atomic interactions so precisely • that some atoms stick together whereas others slide/move freely? • Fluctuations become relatively more important as size decreases • Quantum phenomena become • inescapable at atomic scales: • wave/particle duality, tunneling, • probabilistic vs deterministic • behaviour,…

20. Many pieces of basic science missing Atomic-level control over manufacturing is chemistry! Combinations of atoms and geometries are constrained by properties of elements and chemical bonding We cannot make arbitrary structures and compositions —even relatively simple structures can be very hard to make! cubane (explosive)

21. Biology as a template Biological systems are most effective and efficient manufacturing systems known: DNA polymerase: reliable replication, with error rate ~ 1 in 10,000,000,000 F1F0 ATP synthase: most efficient motor known (~90-100%)

22. Biology as a template Based on simple processes (e.g. polymerisation) Create one basic geometry (linear chains) Rely on self-interactions to generate functional structures automatically (“self-assembly”, “folding” in biology) But we still can’t reliably predict folding for known structures after decades of intensive research! How do we design, de novo, both novel chemistries or functions, and the folds protein folds to achieve them?

23. Yet another fundamental roadblock: heterogeneity How can one manufacture complex assemblies efficiently and reliably without uniform, quality parts? One can’t! As in regular manufacturing, heterogeneity inhibits complexity—need standardised, interchangeable parts Self-assembly is statistical, not deterministic: will always yield mixtures and distributions of products Complex processes with multiple steps: need reliable yield above all 1 step: 97% correct yield 20 steps: 50% worthless junk!

24. Comparisons of heterogeneity Boltzmann entropy (disorder): Shannon entropy (information): Define generalised negentropy: Taq polymerase optimised PCR nanoparticle size dispersion transcription crystal purity DNA replication 0 5 10 15 20 25 30 digital computing (> 50) polymer dispersion precision machining book typesetting telescope mirror integrated circuit components human typing

25. Solutions 1. Do it right in the first place Strong driving force (thermodynamics) 2. Fix it up later Error correction mechanism (kinetics) 3. Ignore it Fault-tolerant architectures

26. What is “nanotechnology”? Encompasses

27. Current areas of research

29. Current applications