Thirty Essential Nanotechnology Studies - #9
Overview of all studies: Because of the largely 
unexpected transformational power of molecular manufacturing, it is urgent to 
understand the issues raised. To date, there has not been anything approaching 
an adequate study of these issues. CRN's recommended series of
thirty essential studies 
is organized into five sections, covering fundamental theory, possible 
technological capabilities, bootstrapping potential, product capabilities, and 
policy questions. Several preliminary conclusions are stated, and because our 
understanding points to a crisis, a parallel process of conducting the studies 
is urged.  
CRN is actively looking for researchers interested in 
performing or assisting with this work. Please contact CRN Research Director
Chris Phoenix if you would like more information or if you have comments on 
the proposed studies. 
  
    | Study #9 | What 
    will be required to develop biological programmable manufacturing and 
    products? | 
  
    |  | This study would 
    explore the various steps involved in harnessing biology to produce 
    engineered products. [Answers in italics are provided by
    Robert Bradbury.]
 | 
  
    | Subquestion | How much 
    time and effort would be required to develop the ability to design 
    predictable protein folding, possibly by introducing novel amino acids? | 
  
    | Preliminary answer | Unknown, but a 
    novel protein fold has been successfully designed and tested. Increasing 
    computer power will make this rapidly easier. | 
  
    | It would not 
    be difficult to integrate novel amino acids using a standard protein 
    synthesis robot. It is more difficult to integrate to integrate them into 
    bacteria, but it has been done. | 
  
    | Subquestion | How 
    difficult would it be to automate all steps of new-protein synthesis? How 
    long would a fully automated system need to produce and characterize a new 
    protein? | 
  
    | Preliminary answer | New protein 
    synthesis is already automated (its a volume/cost issue that can be a 
    hang-up -- which is why bacteria are used to produce things like insulin, 
    antibiotics, etc.). The NSF is pushing rapidly on the automation of the 
    characterization problem (everything from X-ray crystallography to computers 
    figuring out the structure). I've read that they are trying to push it to 
    30,000 structures per year. Though I'm not sure if I can believe that number 
    -- if you look at the growth of the contents of PDB it may be a reality in 
    the near future. | 
  
    |  | There are 
    structures that are difficult to characterize -- these are usually proteins 
    that normally reside in cell membranes of one form or another. So it's a 
    limited subset -- perhaps 20-30% of all proteins. Some novel techniques have 
    been reported for dealing with this but this is ultimately just going to 
    require a lot of work and clever ideas. | 
  
    | Subquestion | What 
    software support must be developed to allow design and testing of novel 
    protein-based machines? | 
  
    | Preliminary answer | Tough question 
    -- we already have the software to design proteins (and the machines to 
    manufacture at least the smaller ones). Testing isn't really a problem. The 
    problem is the creation of a 'novel' machine design. | 
  
    | Subquestion | How much 
    time and/or research will be required before we know how cell 
    signaling/differentiation/gene expression works? | 
  
    | Preliminary answer | We know how 
    gene expression works reasonably well (something like three classes of 
    transcription factors, the structures of which tend to be very standardized, 
    etc.). We also know a lot about signaling and differentiation. We've 
    got hundreds of extracellular molecules and receptors pinned down at this 
    point. The problem is the molecules involved within the cell from the 
    membrane to the nucleus. These are very complex. There is a company in 
    Germany that has worked out much of this in yeast and the #1 priority on the 
    NIH Nanomedicine goal list is to extend this to determine all of the protein 
    complexes in humans. | 
  
    | Subquestion | How can cell 
    toxicity or metabolic interference from novel chemicals be predicted and 
    avoided? | 
  
    | Preliminary answer | This is relevant 
    because one method of protein synthesis involves using gene-spliced cells to 
    synthesize the protein. However, there are ways of manufacturing proteins 
    that do not require cells. | 
  
    | The simple 
    answer is knowledge of the structures of most if not all of the enzymes, 
    receptors, etc. in the body, knowledge of the structure of the novel 
    chemicals and a heck of a lot of computer power to see when/how the 
    structures can interfere. A more complex answer would involve actual 
    toxicity tests at a MEMS scale level to determine when chemicals interfere 
    with the functioning of a protein. (This isn't too different from the work 
    that has been done to synthesize large chemical/drug libraries -- but 
    requires that one understand the metabolic pathways involved and devise 
    individual tests to see when there is interference.) | 
  
    | Conclusion | This deserves further investigation. 
 | 
  
    | Other studies | 1. 
    Is 
    mechanically guided chemistry a viable basis for a manufacturing technology? 2. To what extent is molecular manufacturing counterintuitive and 
    underappreciated in a way that causes underestimation of its importance?
 3. What is 
    the performance and potential of diamondoid machine-phase chemical 
    manufacturing and products?
 4. What is the performance and potential of biological programmable 
    manufacturing and products?
 5. What is the performance and potential of nucleic acid 
    manufacturing and products?
 6. What other chemistries and options should be studied?
 7. What 
    applicable sensing, manipulation, and fabrication tools exist?
 8. What will be required to develop diamondoid machine-phase chemical 
    manufacturing and products?
 
 10. What will be required to develop nucleic acid manufacturing and 
    products?
 11. How rapidly will the cost of development decrease?
 12. How could an effective development program be structured?
 13. What is 
    the probable capability of the manufacturing system?
 14. How capable will the products be?
 15. What will the products cost?
 16. How rapidly could products be designed?
 17. Which 
    of today's products will the system make more accessible or cheaper?
 18. What new products will the system make accessible?
 19. What impact will the system have on production and distribution?
 20. What effect will molecular manufacturing have on military and 
    government capability and planning, considering the implications of arms 
    races and unbalanced development?
 21. What effect will this have on macro- and microeconomics?
 22. How can proliferation and use of nanofactories and their products 
    be limited?
 23. What effect will this have on policing?
 24. What beneficial or desirable effects could this have?
 25. What effect could this have on civil rights and liberties?
 26. What are the disaster/disruption scenarios?
 27. What effect could this have on geopolitics?
 28. What policies toward development of molecular manufacturing does 
    all this suggest?
 29. What policies toward administration of 
    molecular manufacturing does all this suggest?
 30. How can appropriate policy be made and implemented?
 
 | 
  
    | Studies should begin 
    immediately. | The situation is 
    extremely urgent. The stakes are unprecedented, and the world is unprepared. 
    The basic findings of these studies should be verified as rapidly as 
    possible (months, not years). Policy preparation and planning for 
    implementation, likely including a crash development program, should begin 
    immediately. |