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Genomics, Computing, Economics & Society. 10 AM Tue 20-Sep 2005. MIT-OCW Health Sciences & Technology 508 Harvard Biophysics 101 Economics , Public Policy , Business , Health Policy For more info see: http://karma.med.harvard.edu/wiki/Biophysics_101.
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Genomics, Computing, Economics & Society 10 AM Tue 20-Sep 2005 MIT-OCW Health Sciences & Technology 508 Harvard Biophysics 101 Economics, Public Policy, Business, Health Policy For more info see: http://karma.med.harvard.edu/wiki/Biophysics_101
Genomics, Computing, Economics & SocietyCourse plan Each student will participate in a class-wide project to provide decision-making tools for global/local technology development and deployment. Each will have a web page or wiki describing and updating their part of project going by the second class. Grades will be based on 1) participation (round robin) & project (cross-referenced pages) 2) critiques of each others components No prerequisites. But it is assumed that each of you brings some expertise to be integrated with the goals and talents of other team members. Each student should make this clear at the start of the project and update it as the course proceeds.
101: '99-'03 Simple to Complex '05 Complex to Simple • '03 5 problem sets & project • '05 Project starts on day 1 • '03 one 2 hr ppt lecture + 1.5 hr section per week • '05 two 1.5 hr discussion (may include 30' ppt) • '03 Project teams or 1 or two students • '05 Project team of all students & TFs • '03 Choice of two campuses & streaming video • '05 Less choice • '03 Tools: Perl & Mathematica • '05 Wiki (& anything else)
Previous class projects André Catic, Cal Collins, George Church, Hidde Ploegh, HL (2004) Preferred in vivo ubiquitination sites. Bioinformatics 20: 3302-7. Andrew Tolonen, Dinu Albeanu, Julia Corbett, Heather Handley, Charlotte Henson & Pratap Malik (2002) Optimized in situ construction of oligomers on an array surface. Nucleic Acids Research, 30: e107 Hui Ge, George Church, Marc Vidal (2001) Correlation between transcriptome and interactome data obtained from S. cerevisiae. Nature Genetics, 29:482-6. John Aach, Martha Bulyk, George Church, Jason Comander, Adnan Derti, Jay Shendure(2001) Computational comparison of two draft sequences of the human genome. Nature 409, 856-859.
Bio 101: Genomics & Computational Biology Tue Sep 16Integrate 1: Minimal “Systems”, Statistics, Computing Tue Sep 23 Integrate 2: Biology, comparative genomics, models & evidence, applications Tue Sep 30 DNA 1: Polymorphisms, populations, statistics, pharmacogenomics, databases Tue Oct 06 DNA 2: Dynamic programming, Blast, multi-alignment, HiddenMarkovModels Tue Oct 14 RNA 1: 3D-structure, microarrays, library sequencing & quantitation concepts Tue Oct 21 RNA 2: Clustering by gene or condition, DNA/RNA motifs. Tue Oct 28 Protein 1: 3D structural genomics, homology, dynamics, function & drug design Tue Nov 04 Protein 2: Mass spectrometry, modifications, quantitation of interactions Tue Nov 11 Network 1: Metabolic kinetic & flux balance optimization methods Tue Nov 18 Network 2: Molecular computing, self-assembly, genetic algorithms, neural-nets Tue Nov 25 Network 3: Cellular, developmental, social, ecological & commercial models Tue Dec 02 Project presentations Tue Dec 09 Project Presentations Tue Dec 16 Project Presentations
3 Exponential technologies(synergistic) Computation & Communication (bits/sec) E.coli operons Synthesis (daltons) tRNA urea B12 Analysis (bp/$) telegraph tRNA Shendure J, Mitra R, Varma C, Church GM, 2004 Nature Reviews of Genetics. Carlson 2003 ; Kurzweil 2002; Moore 1965
101: '99-'03 Simple to Complex '05 Complex to Simple • Common ground for conservative, liberal, religious & atheist? • What is life? Should we construct from scratch? • Did life evolve using intelligent design? • When does human life begin? • Stem cells & therapeutic cloning? • Can we compare Apples & oranges? • Should we buy iron-lungs • or polio-vaccine research? • Do we invest in anti-terrorism • or anti-malaria?
Hot buttons Evolution Stem Cells Life extension Eugenics, race Privacy Security, Terrorism Genetically modified organisms - GMOs Intelligent machines Replicating machines Witholding experimental drugs (e.g. HIV & Cancer) Gender Do no harm, abortion
Initial Reading • Limits to Growth, The 30-Year Update by Donella H. Meadows, • Jorgen Randers & Dennis L. Meadows 2004 • Freakonomics by Levitt & Dubner 2005 • As the Future Catches You by Juan Enriquez 2000 • Genetic Programming IV: Routine Human-Competitive Machine • Intelligence by John R. Koza et al. 2003 • Consilience by E.O. Wilson 1998 • Redesigning Humans by Gregory Stock 2002 • Scientific Conquest of Death 2004 • Collapse by Jared Diamond 2005 • The Tipping Point by Malcolm Gladwell 2000 • The Wisdom of Crowds by James Surowiecki 2004 • The Climate Of Man by Elizabeth Kolbert 2005 • Widescale Biodiesel Production from Algae by Michael Briggs, • Synthetic Life by WW Gibbs 2004 • Personalized medicine by Francis S. Collins 2005
It seemed like a good idea at the time. Crops River life Grain trade Livestock Hygeine Insecticides Fertilizer Nuclear Power Tankers Pets Malaria Cholera Yersinia Flu & HIV Polio Silent Spring Anoxic fish TMI, Chernobyl Mussels & sea snakes Australian herbicide http://www.primitivism.com/easter-island.htm
Yucky Leon Kass, chairs the US President's Council on Bioethics, opposes therapeutic cloning and stem cell research via 'yuck' reactions, which he terms 'the wisdom of repugnance' http://groups.msn.com/DebateCriticalThinkingandPhilosophy/killingimmortality.msnw Interracial-marriage: Perez v. Sharp, CA 1948, Loving v. Virginia, U.S. Supreme Court 1967 The Wisdom of Crowds by James Surowiecki 2004
Tacky Not Wicked, Perhaps, but Tacky "First place goes to the regrettable tendency of some groups or institutions to bolster their stock by making extravagant claims in the media .. Refusal to share materials .. Anything that has the look of a publicity stunt or of self-interest --Donald Kennedy Science 297:1237 (2002) "Opinions are like genomes: Everyone has one. I want to show the world that we do not need to fear our genetic information but, rather, that it can be a powerful new tool" --J. Craig Venter Science 299: 1183 (2003) The Washington Post reported on Jun 18, 2005 that Chinese farmers, with the knowledge and support of government officials, used amantadine on chickens as long ago as the late 1990s. The report called the drug use a violation of international livestock guidelines.
The Maslow pyramid, 1943 Transcendence : need to help others find fulfillment Thirst for knowledge & aesthetical order Act Wisdom Knowledge Information Intelligence Memory Capacity
Priorities List 1. 2. 3. 4. 5. 6.
Net3: Global integration • Multi-cellular models -- e.g. sensory integration • Systems biology, simulation & integration • Organ systems • Multi-organism - Ecological modeling • predator/prey - host/parasite - HIV • Global & socioeconomic considerations • Education • Model evaluation & sharing
Inheritance is not just DNA Current 26720 km/h 10,912 m pm-Mm 3-1900oK 5000 1017 most tissues Past Locomotion 50 Ocean depth 75m Visible l .4-.7 m Temperature 275-370 Memory years 20 Memory bits 109 Cell therapy 0 http://www.techworld.com/opsys/features/index.cfm?fuseaction=displayfeatures&featureid=467&page=1&pagepos=5 http://www.merkle.com/humanMemory.html
Energy & CO2 Sequestration Humans consume 2kW per person = 1010 kW. Sunlight hits the earth at 40,000 times that rate (70% ocean). CO2 370 ppm = 730 x1015 g globally, increase ~3 x1015 /yr. Ocean productivity = ~100 x1015 g CO2/yr … due to Autotrophs: 1026 Prochlorococcus cells globally (108 per liter) Sequestration v. respiration v. use: heterotrophs (Pelagibacter), phages, predators (Maxillopoda, Malacostraca, herring) 0.1 mm 0.1 m 6 cm http://www.gsfc.nasa.gov/gsfc/service/gallery/fact_sheets/earthsci/terra/earths_energy_balance.htm http://clear.eawag.ch/models/optionenE.html http://en.wikipedia.org/wiki/Copepod Morris et al. Nature 2002 Dec 19-26;420(6917):806-10. http://hosting.uaa.alaska.edu/mhines/biol468/pages/carbon.html http://www.aeiveos.com/~bradbury/Papers/PhotosyntheticEfficiency.html
More on global carbon 7.6 g of C m^-2 year^-1 If multiplied by the Ocean area (3.6e8 km2) = 2.7E15 g C = 1E16 g CO2 Giant Larvacean Houses: Rapid Carbon Transport to the Deep Sea Floor Bruce H. Robison,* Kim R. Reisenbichler, Rob E. Sherlock http://www.planktos.com/oceanscience.htm http://www.fisherycrisis.com/strangelove.html
Responsible Conduct In Research "If scientists find that their discoveries have implications for some important aspect of public affairs, they have a responsibility to call attention to the public issues involved .. A good example is the response of biologists to the development of recombinant DNA technologies -- first calling for a temporary moratorium on the research and then helping to set up a regulatory mechanism to ensure its safety." http://www.aaes.org/membership/index.asp http://www.nap.edu/readingroom/books/obas/
Safer biology via synthetic biology • Systems modeling • HiFi gene replacement • Inexpensive bio-weather-map custom biosensors • (airborne & medical fluids), • International bio-supply-chain licensing • (min research impact, max surveillance) • Metabolic dependencies prevent survival • outside of controlled environments • Multi-epitope vaccines & biosynthetic drugs. • Cells resistant to most existing viruses • via codon changes difficulty see: arep.med.harvard.edu/SBP
Genome Analysis Policy • Insurance/employment: What probability & level of advantage can be hidden/examined? • Individual/group stigma • Choice, stem cells, cloning • Privacy & transparency NHGRI/DOE ELSI, Genetic Screening Study Group
"Open-source" Genome-Phenome Project • Are information-rich resources (e.g. facial imaging & • genome sequence) really anonymous? • What are the risks and benefits of "open-source"? • Prototypes for integrating biomedical data. • What level of training is needed to give informed consent on • open-ended studies? • Harvard Medical School IRB Human Subjects protocol • submitted 16-Sep-2004.
Think globally; act locally Lithosphere (0.2% C, 75% SiO2) 110 C at 4 km Diameter = 1.3e6 m = 5e22 g (5000 species / g soil) Biosphere 3e15 g (dry wt. marine); 2e18 g (land) Microbial hydrosphere 1.4e21 ml = 1e27 cells = 4e33 bp Anthrosphere (23% C) = 6e23 cells = 4e32 bp. fig
CO2 100 ppmv increase 4x1013 kW of sunlight hits earth per year. We consume 2kW per person* 6x109 = 1010 kW. CO2 >370 ppm = 730 x1015 g globally, increase ~3 x1015 /yr. Ocean productivity = ~100 x1015 g/yr. www.gsfc.nasa.gov/gsfc/service/gallery/fact_sheets/earthsci/terra/earths_energy_balance.htm http://clear.eawag.ch/models/optionenE.html Morris et al. Nature 2002 Dec 19-26;420(6917):806-10. http://hosting.uaa.alaska.edu/mhines/biol468/pages/carbon.html http://jan.ucc.nau.edu/~doetqp-p/courses/env470/Lectures/lec41/Lec41.htm
Models for education & decision-making Improve our ability to deal with: Uncertainty Complexity Quantitation Exceptions (collect and cherish) Comparisons of diverse entities Translation & integration Continuity over time
Biophilia & Consilience Biophilia -- the connections that human beings subconsciously make with other living beings. (Cute animals, snake dreams, therapeutic greenery & natural sounds …) Consilience - Long-separated fields come together and create new insights; e.g. chemistry & genetics created the powerful new science of molecular biology. Is all human endeavor, from religious feeling to financial markets to fine arts, ripe for explaining by hard science? How might genomics & computational biology contribute? Kellert & Wilson 1993 The Biophilia Hypothesis. E. O. Wilson 1999 - Consilience: The Unity of Knowledge
Prediction & supercomputers Weather http://www.top500.org/ Evolution http://www.leaderu.com/common/colson-kansas.html http://www.findarticles.com/p/articles/mi_m2843/is_2_29/ai_n13628921/pg_3 http://www.millerandlevine.com/km/evol/Moths/moths.html