MIT-OCW Health Sciences & Technology 508 Harvard Biophysics 101 EconomicsEconomics, Public Policy, Business, Health PolicyPublic PolicyBusinessHealth Policy For more info see: 10 AM Tue 20-Sep 2005 Genomics, Computing, Economics & Society

Genomics, Computing, Economics & Society Course 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 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: 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: 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,

Tue Sep 16 Integrate 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 Bio 101: Genomics & Computational Biology

3 Exponential technologies (synergistic) Shendure J, Mitra R, Varma C, Church GM, 2004 Nature Reviews of Genetics. Carlson 2003 ; Kurzweil 2002; Moore 1965 urea E.coli B12 tRNA operons telegraph Computation & Communication (bits/sec) Synthesis (daltons) Analysis (bp/$) tRNA

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 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 2005The Climate Of Man Widescale Biodiesel Production from Algae by Michael Briggs,Widescale Biodiesel Production from Algae Synthetic Life by WW Gibbs 2004Synthetic Life Personalized medicine by Francis S. Collins 2005 Personalized medicine

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

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' 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 Act Wisdom Knowledge Information Intelligence Memory Capacity Transcendence : need to help others find fulfillment Thirst for knowledge & aesthetical order

Priorities List

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Potential slides for subsequent classes

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

Past Locomotion50 Ocean depth75m Visible.4-.7  Temperature Memory years20 Memory bits10 9 Cell therapy Current km/h 10,912 m pm-Mm o K most tissues

Humans consume 2kW per person = kW. Sunlight hits the earth at 40,000 times that rate (70% ocean). CO ppm = 730 x10 15 g globally, increase ~3 x10 15 /yr. Ocean productivity = ~100 x10 15 g CO 2 /yr … due to Autotrophs: Prochlorococcus cells globally (10 8 per liter) Sequestration v. respiration v. use: heterotrophs (Pelagibacter), phages, predators (Maxillopoda, Malacostraca, herring) Energy & CO 2 Sequestration Morris et al. Nature 2002 Dec 19-26;420(6917):  0.1 mm 6 cm

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

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."

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 see: arep.med.harvard.edu/SBP difficulty

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

Anonymity, privacy, disclosure, identity

"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% SiO 2 ) 110 C at 4 km Diameter = 1.3e6 m = 5e22 g (5000 species / g soil) BiosphereBiosphere 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

CO ppmv increase 4x10 13 kW of sunlight hits earth per year. We consume 2kW per person* 6x10 9 = kW. CO 2 >370 ppm = 730 x10 15 g globally, increase ~3 x10 15 /yr. Ocean productivity = ~100 x10 15 g/yr. s/earthsci/terra/earths_energy_balance.htm Morris et al. Nature 2002 Dec ;420(6917): s/carbon.html

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 Kellert & Wilson 1993 The Biophilia Hypothesis.The Biophilia Hypothesis. E. O. Wilson Consilience: The Unity of KnowledgeConsilience: The Unity of Knowledge 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? Biophilia -- the connections that human beings subconsciously make with other living beings. (Cute animals, snake dreams, therapeutic greenery & natural sounds …) How might genomics & computational biology contribute?

Prediction & supercomputers Weather Evolution /pg_3