George M. Church

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George McDonald Church
Church 8-Jul-2010.jpg
George Church during the Presidential Commission for the Study of Bioethical Issues 8-Jul-2010
Born (1954-08-28) August 28, 1954 (age 60)[1]
MacDill Air Force Base, Florida[1]
Residence Boston, Massachusetts
Citizenship United States
Nationality United States
Fields Genetics
Institutions Harvard University
Massachusetts Institute of Technology (MIT)
Alma mater Duke University (BA in Chemistry, BA in Zoology)
Harvard University (PhD in biochemistry and molecular biology)
Thesis Genetic Elements within Yeast Mitochondrial and Mouse Immunoglobulin Introns (1984)
Doctoral advisor Walter Gilbert
Notable awards Bower Award and Prize for Achievement in Science of the Franklin Institute
Website
arep.med.harvard.edu/gmc

George McDonald Church (born August 28, 1954) is an American geneticist, molecular engineer, and chemist. He is Professor of Genetics[2] at Harvard Medical School, Professor of Health Sciences and Technology[3] at Harvard and MIT, and founding core member[4] of the Wyss Institute for Biologically Inspired Engineering at Harvard University.[5][6][7] He is widely regarded as a pioneer in personal genomics and synthetic biology.[8] He is married[9] to fellow Harvard Medical School faculty in genetics, Ting Wu.[10]

Training and career[edit]

Church attended high school at the Phillips Academy from 1968 to 1972. He then studied at Duke University and completed undergraduate BA degrees in Chemistry and Zoology in two years. During this time he began working with Sung-Hou Kim, continuing this work into graduate school at Duke, while co-authoring five research publications on models for DNA-protein interactions and the first 3D structure of a folded nucleic acid. During his graduate studies, he transferred to Harvard University, graduating with a PhD in biochemistry and molecular biology in 1984 for work with Walter Gilbert on Genetic Elements within Yeast Mitochondrial and Mouse Immunoglobulin Introns.[11][12] In 1984 he was one of the first employees at Biogen and then an LSRF fellow at UCSF with Gail R. Martin. He joined the Harvard Medical School Faculty in 1986. He is a senior editor[13] for Molecular Systems Biology. Church has co-authored more than 290 publications and 50 patents.[14] He is director of the U.S. Department of Energy Center on Bioenergy Technology at Harvard[15] and director of the National Institutes of Health (NHGRI) Center of Excellence in Genomic Science (CEGS) at Harvard.[16]

Genome sequencing and interpretation technologies[edit]

With Walter Gilbert, Church published the first direct genomic sequencing method in 1984.[17][18] Described in that publication were the cyclic application of fluids to a solid phase alternating with imaging, plus avoidance of bacterial cloning, strategies that are still used in today's dominant Next-Generation Sequencing technologies. These technologies began to have an impact on genome-scale sequencing 2005.[19] Church also helped initiate the Human Genome Project in 1984.[20] He invented the broadly applied concepts of molecular multiplexing and barcode tags.[21] Technology transfer from his Harvard laboratory of automated sequencing & software to Genome Therapeutics Corp. resulted in the first bacterial genome sequence and first commercial genome (the human pathogen Helicobacter pylori) in 1994.[22] Church was also co-inventor of nanopore sequencing in 1995, which are now commercially available (e.g. Oxford Nanopore Technologies), but not in the form embodied in Church's contribution to the original patents.[23][broken citation]

To aid in the interpretation and sharing of genomes, Church, in 2005, initiated the Personal Genome Project (PGP),[24] which provides the world’s only open-access human genome and trait data sets.[25][26][27] Eight trios (mother, father, and child) from the Personal Genome Project are in the process of being chosen to act as the primary genome standards (Reference Materials) for the NIST+FDA genomeinabottle.org program.[28]

Synthetic biology and genome engineering[edit]

Image of Church portraying his role in the Personal Genome Project.

He has co-developed numerous "genome engineering" technologies since 1997 via either general homologous recombination (recA and lambda-red) [29] or via sequence-specific nucleases.[30] Since 2004, his team has developed use of DNA array (aka DNA chip) synthesizers for combinatorial libraries and assembling large genome segments.[31] He co-developed Multiplex Automated Genome Engineering (MAGE) and optimized CRISPR/Cas9 discovered by Jennifer Doudna and Emanuelle Charpentier for engineering a variety of genomes ranging from yeast to human.[30] His laboratory's use of CRISPR in human induced pluripotent stem cells (hiPS) is the latest contender for precise gene therapy.[32]

His team is the first to tackle a genome-scale change in the genetic code.[33] This was done in a 4.7 million basepair genome of an industrially useful microbe (E. coli) with the goal of making a safer and more productive strain; this strain uses non-proteinogenic amino acids in proteins and is metabolically and genetically isolated from other species.

He has co-invented several novel uses for DNA, including detectors for dark matter -- Weakly interacting massive particles (WIMPs),[34] anti-cancer "nano-robots",[35] and strategies for digital data storage that are over a million times denser than conventional disk drives.[36] Together with polymerase, DNA can be used to sense and store variation in photons, nucleotides, or ions.[37]

The BRAIN initiative[edit]

He was part of a team of six[37] who, in a 2012 scientific commentary, proposed a Brain Activity Map, later named BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies).[38] They outlined a variety of specific experimental techniques that might be used to achieve what they termed a "functional connectome", as well as new technologies that will have to be developed in the course of the project,[37] including wireless, minimally invasive methods to detect and manipulate neuronal activity, either utilizing microelectronics or synthetic biology. In one such proposed method, enzymatically produced DNA would serve as a "ticker tape record" of neuronal activity.[37][39]

Technology transfer and translational impact[edit]

Church has co-founded 9 companies, including Warp Drive Bio (natural products, 2011, with Greg Verdine and James Wells), Alacris (cancer systems therapeutics, 2010, with Hans Lehrach, Bernhard Herrmann, and Shahid Imran), Knome (human genomics, 2007, with Jorge Conde and Sundar Subramaniam),[40] Pathogenica (microbe and viral NGS diagnostics, 2009, with Yemi Adesokan),[41] AbVitro (immunomes, 2010, with Francois Vigneault), Gen9 Bio (synthetic biology, 2009, with Joseph Jacobson and Drew Endy), EnEvolv (Genome Engineering), Joule Unlimited (SolarFuels, 2007, with Noubar Afeyan and David Berry), and LS9 (green chemistry, 2005, with Chris Somerville, Jay Keasling, Vinod Khosla, Noubar Afeyan, and David Berry)[8][42][43]

He has participated in technology development, licensing patents and advising most of the Next-Generation Sequencing companies, including Complete Genomics, Life Technologies, Illumina, Danaher Corporation, Roche Diagnostics, Pacific Biosciences, Genia, and Nabsys.[43]

Bioethics, education, and public policy[edit]

Support of open consent[edit]

Church spearheaded the concept and implementation of open access sequencing hardware[44] and shareable human medical data.[27] He has noted the potential for re-identification of human research participants and the tendency for consent forms to be opaque – proposing an alternative "open consent" mechanism.[25][26] He has participated in the Presidential Commission for the Study of Bioethical Issues,[45] cautioning about the risk of synthetic DNA and proposing risk-reduction via licensing and surveillance.[46][47] His laboratory has a major bio-safety engineering focus.[33]

Church at TED 2010, picture by Steve Jurvetson.

Support of open education[edit]

He has been an early advocate of online, open education since 2002.[3] He is advisor to the Personal Genetics Education Project[48] and has spent a day teaching at The Jemicy School.[49] He has championed citizen science, especially in the fields of synthetic biology and personal genomics.[26] Since 2008, his team has been hosting an annual Genomes, Environments and Traits (GET) Conference with free online videos.[50]

Support of vegan lifestyle[edit]

Church follows a vegan lifestyle for reasons concerning health, environmental and moral issues surrounding factory farming. When asked about his dietary choice Church replied,

"I've been vegan off-and-on since 1974 when I was inspired by participating in an MIT nutritional study, and quite strictly since 2004. My four reasons have been: medical (cholesterol in fish & dairy), energy conservation (up to 20-fold impact), cruelty ("organic" animals are deprived of medicines that humans use), and risks of spreading pathogens (not just the flu)...Veganism is an issue for which personal and global love of life, health and wealth align. It's a pity to lose parts of our humanity and planet just due to a lack of recipes."[51]

In popular culture[edit]

In October 2012, Church published a book that he wrote with Ed Regis entitled Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves.[52] This was on a top ten Science book list.[53] He has participated in over 500 news interviews and 50 videos including TED, TEDx, TEDMED, PopSci, EG, and popular television programs including The Colbert Report, Charlie Rose, Faces of America, and PBS NOVA.[54] He is a regular contributor to Edge.org publications and videos.[55]

In response to a question from Der Spiegel, Church speculated that it could be technically possible to make a Neanderthal by reconstructing the DNA of a Neanderthal and modifying living human cells accordingly.[56] Other media such as The Daily Mail fabricated a "Want-Ad" and quote for Church as having said: "Now I need an adventurous female human." [57] Church pointed out that he was not working on such a project.[58][59]

In the context of the Personal Genome Project, journalists at Forbes and Wired have noted Church's openness about his health issues, including dyslexia, narcolepsy, and high cholesterol (one of the motivations for his vegan diet).[60][61]

Honors[edit]

In 2011, Church was awarded the Bower Award and Prize for Achievement in Science of the Franklin Institute (awarded once every 7 years in Life Sciences).[62] Other honors include the American Society for Microbiology Promega Biotechnology Research Award in 2009, the Triennial International Steven Hoogendijk Award in 2010, the Scientific American Top 50 twice (for “Designing artificial life” in 2005 and "The $1000 genome" in 2006).[63][64] Newsweek picked Church for their 2008 “Power of Ideas” recognition in the category of Medicine (for the Personal Genome Project).[65] In September 2010, Dr Church was honored for his work in Genetics with the Mass High Tech All-Star Award.[66]

He was elected to both the National Academy of Sciences (in 2011) [67] and the National Academy of Engineering (in 2012).[68] He is a member of the Research Advisory Board of SENS Research Foundation.[69]

References[edit]

  1. ^ a b "Church, George". Biography Reference Bank. The H. W. Wilson Company. 2010. Retrieved 2011-12-10. 
  2. ^ "Harvard Medical School Genetics Faculty". Retrieved 25 May 2013. 
  3. ^ a b "OCW HST.508 Genomics and Computational Biology". 2002. 
  4. ^ "Wyss Institute Core Faculty". Retrieved 25 May 2013. 
  5. ^ "Harvard Molecular Technology Group & Lipper Center for Computational Genetics". Retrieved 2011-07-05. 
  6. ^ "George M. Church Personal History & Interests (Unauthorized autobiography & Infrequently Asked Questions)". Retrieved 2011-07-05. 
  7. ^ Nair P (2012). "Profile of George M. Church". Proceedings of the National Academy of Sciences. doi:10.1073/pnas.1204148109. PMID 22474375. 
  8. ^ a b Duncan, David (7 Jun 2010). "Scientist at Work: George M. Church - On a Mission to Sequence the Genomes of 100,000 People". The New York Times. Retrieved 2010-08-18. 
  9. ^ "Do inventors get enough respect in science?". The Boston Globe. 2013-02-07. 
  10. ^ "Ting (C-ting) Wu, Ph.D.". Department of Genetics, Harvard Medical School. 
  11. ^ Church, George (1984). Genetic Elements within Yeast Mitochondrial and Mouse Immunoglobulin Introns (Sequence, Enhancer, Technique) (PhD thesis). Harvard University. 
  12. ^ Speaker Biography - George M. Church
  13. ^ "About the editors: Molecular Systems Biology". Retrieved 2011-07-05. 
  14. ^ "Church lab: publications and patents". Harvard Medical School. Retrieved July 18, 2012. 
  15. ^ "DOE Genomes to Life Center". Retrieved 25 May 2013. 
  16. ^ "NIH NHGRI Centers of Excellence in Genomic Science Awards (CEGS)". 1 Aug 2011. 
  17. ^ Church GM, Gilbert W (1984). "Genomic sequencing". Proceedings of the National Academy of Sciences of the United States of America 81 (7): 1991–1995. doi:10.1073/pnas.81.7.1991. PMC 345422. PMID 6326095. 
  18. ^ Saluz HP, Jiricny J, Jost JP (1986). "Genomic sequencing reveals a positive correlation between the kinetics of strand-specific DNA demethylation of the overlapping estradiol/glucocorticoid-receptor binding sites and the rate of avian vitellogenin mRNA synthesis". Proc. Natl. Acad. Sci. U.S.A. 83 (19): 7167–71. doi:10.1073/pnas.83.19.7167. PMC 386676. PMID 3463957. "Direct genomic sequencing, first described by Church and Gilbert (15) and further developed in our laboratory (16), overcomes the disadvantages inherent to the use of restriction enzymes." 
  19. ^ Shendure J, Porreca GJ, Reppas NB, Lin X, McCutcheon JP, Rosenbaum AM, Wang MD, Zhang K, Mitra RD, Church GM (2005). "Accurate Multiplex Polony Sequencing of an Evolved Bacterial Genome". Science 309 (5741): 1728–32. doi:10.1126/science.1117389. PMID 16081699. 
  20. ^ Cook-Deegan RM (1989). "The Alta summit, December 1984". Genomics 5 (3): 661–663. doi:10.1016/0888-7543(89)90042-6. PMID 2613249. 
  21. ^ Church GM, Kieffer-Higgins S (1988). "Multiplex DNA sequencing". Science 240 (4849): 185–188. doi:10.1126/science.3353714. PMID 3353714. 
  22. ^ "Capitalizing on the genome". Nature Genetics 13 (1): 1–5. 1996. doi:10.1038/ng0596-1. PMID 8673083. 
  23. ^ "Genia Technologies Collaborates with Professors Jingyue Ju at Columbia and George Church at Harvard to Develop a Nanopore-based Sequencing Platform". 3 Oct 2012. 
  24. ^ Church GM (2005). "The Personal Genome Project". Molecular Systems Biology 1 (1): E1–E3. doi:10.1038/msb4100040. PMC 1681452. PMID 16729065. 
  25. ^ a b Ian L. Marpuri (8 Apr 2013). "Researchers explore genomic data privacy and risk (NIH NHGRI)". 
  26. ^ a b c Angrist M (Nov 2009). "Eyes wide open: the Personal Genome Project, citizen science and veracity in informed consent". Personalized Medicine 6 (6): 691–699. doi:10.2217/pme.09.48. PMC 3275804. PMID 22328898. 
  27. ^ a b "Personal Genome Project". Retrieved 25 May 2013. 
  28. ^ "Okay, You've Sequenced My Genome: Are You Sure You Got it Right?". NGS Leaders. 
  29. ^ Link AJ, Phillips D, Church GM (1997). "Methods for generating precise deletions and insertions in the genome of wild-type Escherichia coli: Application to open reading frame characterization". Journal of bacteriology 179 (20): 6228–6237. PMC 179534. PMID 9335267. 
  30. ^ a b Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM (Feb 15, 2013). "RNA-guided human genome engineering via Cas9". Science 339 (6121): 823–6. doi:10.1126/science.1232033. PMC 3712628. PMID 23287722. 
  31. ^ Tian J, Gong H, Sheng N, Zhou X, Gulari E, Gao X, Church G (2004). "Accurate Multiplex Gene Synthesis from Programmable DNA Chips". Nature 432 (7020): 1050–4. doi:10.1038/nature03151. PMID 15616567. 
  32. ^ Matthew Herper (19 Mar 2013). "This Protein Could Change Biotech Forever". Forbes. 
  33. ^ a b Isaacs FJ, Carr PA, Wang HH, Lajoie MJ, Sterling B, Kraal L, Tolonen AC, Gianoulis TA, Goodman DB, Reppas NB, Emig CJ, Bang D, Hwang SJ, Jewett MC, Jacobson JM, Church GM (2011). "Precise Manipulation of Chromosomes in vivo Enables Genome-wide Codon Replacement". Science 333 (6040): 348–53. doi:10.1126/science.1205822. PMID 21764749. 
  34. ^ "Revolutionary 'DNA Tracking Chamber' Could Detect Dark Matter". Technology Review. 2 Jul 2012. 
  35. ^ Belle Dumé (17 Feb 2012). "DNA nanorobot delivers drugs". Physics World. 
  36. ^ Robert Lee Hotz (16 Aug 2012). "Future of Data: Encoded in DNA". Wall Street Journal. 
  37. ^ a b c d Alivisatos AP, Chun M, Church GM, Greenspan RJ, Roukes ML, Yuste R (June 2012). "The Brain Activity Map Project and the Challenge of Functional Connectomics". Neuron 74 (6): 970–974. doi:10.1016/j.neuron.2012.06.006. PMID 22726828. Retrieved February 22, 2013. 
  38. ^ John Markoff (17 Feb 2013). "Obama Seeking to Boost Study of Human Brain". NY Times. 
  39. ^ Zamft BM, Marblestone AH, Kording K, Schmidt D, Martin-Alarcon D, Tyo K, Boyden ES, Church G (August 2012). "Measuring Cation Dependent DNA Polymerase Fidelity Landscapes by Deep Sequencing". PLOS ONE 7 (8): e43876. doi:10.1371/journal.pone.0043876. PMID 22928047. Retrieved February 27, 2013. 
  40. ^ Dickinson, Boonsri (2010-06-10). "Geneticist George Church: Sequencing human genome ‘high priority’ for China". Smart Planet. Retrieved 2010-08-18. 
  41. ^ Julia Karow (2010-07-06). "Pathogenica Bets on Next-Gen Sequencing for Fast, Multiplexed Pathogen Detection". GenomeWeb. Retrieved 2011-09-06. 
  42. ^ "Biofuel startup raises $5 million". San Francisco Business Times. 12 Mar 2007. 
  43. ^ a b "Tech Transfer, Advisory Roles, and Funding Sources". 
  44. ^ "Open, Affordable Sequencing". Retrieved 25 May 2013. 
  45. ^ "Presidential Commission for the Study of Bioethical Issues". 8 Jul 2010. 
  46. ^ "A Synthetic Biohazard Non-proliferation Proposal". Retrieved 25 May 2013. 
  47. ^ Church G (Nov 24, 2005). "Let us go forth and safely multiply". Nature 438 (7067): 423. doi:10.1038/438423a. PMID 16306966. 
  48. ^ "Personal Genetics Education Project". Retrieved 25 May 2013. 
  49. ^ "Jemicy School for Dyslexia, David Malin Lecture". 11 Nov 2010. 
  50. ^ "Genomes, Environments and Traits (GET) Conference". Retrieved 25 May 2013. 
  51. ^ "George Church". Retrieved 17 June 2013. 
  52. ^ Church George (2012). Regenesis. New York: Basic Books. ISBN 0-465-02175-1. 
  53. ^ "The top 10 science books of 2012". NewScientist. 
  54. ^ "Church Lab News". Retrieved 2010-09-08. 
  55. ^ "Church Writings, Master Class and Videos on Edge.org". Retrieved 25 May 2013. 
  56. ^ "How DNA will be construction material of the future". Der Spiegel. 18 Jan 2013. 
  57. ^ "Wanted: 'Adventurous woman' to give birth to Neanderthal man". London: Daily Mail. 20 Jan 2013. 
  58. ^ Gary J. Remal (22 Jan 2013). "Harvard professor blasts Neanderthal clone baby rumor on Web". Boston Herald. 
  59. ^ "Spiegel responds to brouhaha over neanderthal clone". Der Spiegel. 23 Jan 2013. 
  60. ^ Herper, Matthew (27 April 2009). "Going To Church". Forbes Magazine. 
  61. ^ Thomas Goetz (2008-07-08). "How the Personal Genome Project Could Unlock the Mysteries of Life". Wired. 
  62. ^ "Bower Award and Prize for Achievement in Science". Franklin Institute. 2011. Retrieved December 23, 2011. 
  63. ^ "American Society for Microbiology honors George M. Church". 8 Jun 2009. 
  64. ^ "International Steven Hoogendijk Award". 2010. 
  65. ^ "The Power of Ideas". Newsweek. 19 Dec 2008. 
  66. ^ "All-Star Awards". Mass High Tech. 2010-09-08. Retrieved 2010-09-08. 
  67. ^ "National Academy of Sciences Members and Foreign Associates Elected". National Academies. 2011. Retrieved February 17, 2012. 
  68. ^ "National Academy of Engineering Elects 66 Members and 10 Foreign Associates". National Academies. 2012. Retrieved February 17, 2012. 
  69. ^ Zealley, Ben (March 7, 2013). "SRF's Research Advisory Board Welcomes Dr. George Church". Retrieved 18 August 2014.