NOTE
CHAPTER 1: DAWN OF THE BIOLOGICAL AGE
1. Name changed to protect patient’s privacy.
ACKNOWLEDGMENTS
It has been a privilege to work with Michael D’Antonio. Michael’s friendship, patience, and storytelling prowess have converted our conversations about medical science into this book that I hope will convey the purpose-driven creativity that is that process. Michael endured much with indomitable good cheer throughout. His enormous skills as writer and researcher are superseded only by his humanity; I am forever indebted to him and his friendship is much cherished.
A book is the product of every influence in an author’s life, and this is especially true for the people who provide love, friendship, inspiration, and guidance. Kathryn Scadden, the love of my life and my partner in every sense of the word, can be felt in every compassionate passage of this text. Margaret Scadden, Elizabeth Scadden, and Ned Scadden are all here in their distinctively inspiring and deeply virtuous ways: they make every day richer and worthy.
From an early age, I was instructed in matters of humanity and curiosity-driven pursuits by my parents, grandparents, sisters, friends, neighbors and classmates. My sisters encouraged me and while I never had brothers, four people became my brothers in all but blood: Tim Reynolds, Keith Mendelson, Bruce Walker, and Doug Melton. I am a better human because of them.
I am indebted to those who sparked my love of learning and gave me confidence that curiosity could turn to useful action. First and foremost are my parents, my teachers like George Walthoff, my family doctor, Salvatore Baldino, my professors at Bucknell like Michael Payne, John Murphy, and James Carens, my classmate and friend John Richard, my inspirations in medical school Adel Mahmoud, Charles Carpenter, Richard Graham, and George Bernier, and those extraordinary physicians who shaped my medical career like E. Franklin Bunn, David Rosenthal, Marshall Wolf, Eugene Braunwald, George Canellos, Robert Mayer, Robert Schwartz, Jerome Groopman, James Cunningham, John Potts, Kurt lsselbacher, and especially, Bruce Chabner.
It is impossible to pursue science without the material and emotional support of individuals and institutions. I am forever grateful to Gerald and Darlene Jordan for the honor of a Harvard Chair in their name, to John Hess, Wilber and Janet James, Craig and Tracey Huff, Susan and Michael Hazard, and the many donors who have given stem cell science at Harvard and MGH the opportunity to deliver benefit for patients. The leaders of the institutions I have been fortunate to be a part of make an often unsung, but enormous impact on the lives they shape and foster. I thank them and MGH, Harvard, BWH, Case Western Reserve and Bucknell for what they have given me.
Those who been my students or post-doctoral fellows have been an intellectual family whom I treasure and whose success is an ever-expanding source of joy. It has been a privilege to work with them. They include: Barbara Fuller, DVM, Anna Berardi, Ph.D., David Feder, M.D., Andrew Freedman, M.D., Ph.D., Lucia Columbyova, M.D., Michael Franken, M.D., Hongmei Shen, Ph.D., Tao Cheng, M.D., Nadia Carlesso, M.D., Ph.D., Antonio Daga, M.D., Ph.D., Tajiro Ishiyama, M.D., Jason Gardner, Ph.D., Byeong-Chel Lee, Ph.D., Christian Brander, Ph.D., Mark Poznansky, M.D., Ph.D., Richard Evans, M.D., Nobuyuki Miura, M.D., Ph.D., Neil Rodrigues, Ph.D., John Patrick Whelan, M.D., Ph.D., Zhengyu Wang, Ph.D., Paula O’Connor, M.D., Leonor Sarmento, Ph.D., Kenneth Cohen, M.D., Sebastian Stier, M.D., Gregor Adams, Ph.D., Yorikio Saito, M.D., Henry Dong, M.D., Ph.D., Zbigniew Szczepiorkowski, M.D., Ph.D., Robin Mayfield, M.D., Anna Gallazi, M.D., Dipti Patel, M.D., Randolf Forkert, M.D., Paul Robertson, MRCP, Eyal Attar, M.D., Dojun Gohara, Ph.D., Todd Suscovich, Ph.D., Keith Orford, M.D., Ph.D., Dorothy Sipkins, M.D., Ph.D., Chou-Wen Lin, Ph.D., Tong Chen, M.D., Richard Haspel, M.D., Ph.D., Heather Fleming, Ph.D., Viktor Janzen, M.D., Jonas Larsson, M.D., Ph.D., Louise Purton, Ph.D., Siddhartha Mukherjee, M.D., Ph.D., Nathaniel Jeanson, Ph.D., Brian Garrison, Ph.D., Shangqin Guo, Ph.D., Cristina LoCelso, Ph.D., Stephanie Xie, Ph.D., Marc Raaijmakers, M.D., Ph.D., Andre Catic, M.D., Ph.D., Daniela Krause, M.D., Ph.D., Borja Saez, Ph.D., Dongsu Park, Ph.D., Vionnie Yu, Ph.D., Siyi Zhang, Ph.D., Rushdia Yousuf, M.D., Lev Silberstein, M.D., Ph.D., Stephen Sykes, Ph.D., Stephania Lymperi, Ph.D., Gerd Bungartz, Ph.D., Francesca Ferraro, M.D., Ph.D., Jorg Dietrich, M.D., Ph.D., Ying-Hua Wang, Ph.D., Andrew Lane, M.D., Ph.D., David Sykes, M.D., Ph.D., Francois Mercier, M.D., Christine Ragu, Ph.D., Youmna Kfoury, Ph.D., Dongjun Lee, Ph.D., Jonathan Hoggatt, Ph.D., Rahul Palchaudhuri, Ph.D., Julien Cobert, M.D., Ninib Baryawno, Ph.D., Nicolas Severe, Ph.D., Demetrios Kalatzidis, Ph.D., Toshihoko Oki, M.D., Ph.D., Karin Gustafsson, Ph.D., Nisarg Shah, Ph.D., Amir Schjanovich, Ph.D., Nick Van Gastel, Ph.D., Yiping Wang, Ph.D., Azeem Sharda, MS, Cheuk-Him Man, Ph.D., Catherine Rhee, Ph.D., Xiao-Jing Yan, M.D., Ph.D., Adrian Berg, B.S., Phillip Chea, B.S., and Ting Zhao, Ph.D.
It is not possible to thank enough the people who have been partners in making laboratory science and clinical care mesh without daily chaos. My assistant, Lisa Tramontozzi, has been heroic and ever cheerful in keeping the wheels turning. Those before her, including Ellen Kornell and Chris Pasker, also have my special thanks. The Center for Regenerative Medicine at MGH could not exist without the tireless effort, commitment and indefatigable good humor of Dave Machon. Brock Reeve has been a beacon of strength and creative drive for the Harvard Stem Cell Institute. Catherine Link, Willy Lensch, Ph.D. and now Heather Rooke, Ph.D. managed the Department of Stem Cell and Regenerative Biology at Harvard University with exceptional skill and personal touch. I am indebted to them and those they lead for their dedication and friendship.
Finally, colleagues and patients are the greatest source of inspiration and wisdom for anyone in medical research. I cannot name them all nor adequately express how I value their spirited engagement with our shared mission to improve health. Collectively, they are the true wellspring of ideas and motivation. My work in clinical cancer research was made possible by a team that was unparalleled in commitment to giving patients the best possible care. They are Jocelyn Bresnahan, R.N., Walter Howard, P.A., and Kathleen Shea. I would be remiss to not thank one patient in particular, Linda Allen, who has shown how joyful living and serendipity can mean everything, even in Cancerland.
BIBLIOGRAPHY
INTRODUCTION
Bero, Lisa A. “Tobacco Industry Manipulation of Research.” Public Health Reports 120, no. 2 (2005): 200–208.
Hartmaier, Ryan J., Jehad Charo, David Fabrizio, Michael E. Goldberg, Lee A. Albacker, William Pao, and Juliann Chmielecki. “Genomic Analysis of 63,220 Tumors Reveals Insights into Tumor Uniqueness and Targeted Cancer Immunotherapy Strategies.” Genome Medicine 9, no. 1 (2017): 16.
Mukherjee, Siddhartha. The Emperor of All Maladies: A Biography of Cancer. New York: Scribner, 2011.
Nightingale, Stuart L. “Laetrile: The Regulatory Challenge of an Unproven Remedy.” Public Health Reports 99, no. 4 (1984): 333–338.
Public Papers of the Presidents of the United States, Richard Nixon, 1971: Containing the Public Messages, Speeches, and Statements of the President. Washington, D.C.: General Services Administration, 1999. 406–410.
Sinkovics, J. G., R. J. Pienta, J. M. Trujillo, and M. J. Ahearn. “An Immunological Explanation for the Starry Sky Histological Pattern of a Malignant Lymphoma.” Journal of Infectious Diseases 120, no. 2 (1969): 250–254.
CHAPTER 1: DAWN OF THE BIOLOGICAL AGE
Campisi, J. “Aging, Cellular Senescence, and Cancer.” Annual Review of Physiology 75 (2013): 685–705. http://doi.org/10.1146/annurev-physiol-030212-183653.
“Cancer May Be Infectious.” Life, July 22, 1962.
Chedd, Graham. “Threat to U.S. Genetic Engineering.” New Scientist, July 1, 1978, 14.
De Chadarevian, Soraya. “Sequences, Conformation, Information: Biochemists and Molecular Biologists in the 1950s.” Journal of the History of Biology 29, no. 3 (1996): 361–386.
Edelson, Edward. Francis Crick and James Watson: And the Building Blocks of Life. New York: Oxford University Press, 1998.
Falkow,
S. “The Lessons of Asilomar and the H5N1 ‘Affair.’” mBio 3, no. 5 (2012): e00354-12. doi:10.1128/mBio.00354-12.
Goodell, Rae S. “Public Involvement in the DNA Controversy: The Case of Cambridge, Massachusetts.” Science, Technology, & Human Values 4, no. 27 (1979): 36–43.
Jones, James. Bad Blood: The Tuskegee Syphilis Experiment. New and expanded edition. New York: Free Press, 1993.
McCall, Matt. “The Secret Lives of Cadavers: How Lifeless Bodies Become Life-Saving Tools.” National Geographic, July 29, 2016.
McLaughlin-Drubin, Margaret E., and Karl Munger. “Viruses Associated with Human Cancer.” Biochimica et Biophysica Acta 1782, no. 3 (2008): 127–150. doi:10.1016/j.bbadis.2007.12.005.
von Boehmer, Harald. “Thoracic Thymus, Exclusive No Longer.” Science 312, no. 5771 (2006): 206–207.
Weisz, George. “The Emergence of Medical Specialization in the Nineteenth Century.” Bulletin of the History of Medicine 77 (2003): 536–575.
Wiernik, Peter H., John M. Goldman, Janice P. Dutcher, and Robert A. Kyle, eds. Neoplastic Diseases of the Blood. New York: Springer, 2013. 825.
CHAPTER 2: SEEING CANCER
Aptowicz, Cristin O’Keefe. “The Dawn of Modern Anesthesia.” Atlantic, September 4, 2014.
Gill, P. S., et al. “Paclitaxel is safe and effective in the treatment of advanced AIDS-related Kaposi’s sarcoma.” Journal of Clinical Oncology 17, no. 6 (1999): 1876–1883.
Grimes, Jack, et al. “The Roles of Water, Sanitation, and Hygiene in Reducing Schistosomiasis: A Review.” Parasites & Vectors 8 (2015): 156.
Hollingham, Richard. Blood and Guts: A History of Surgery. New York: St. Martin’s Griffin, 2009.
Imber, Gerald. Genius on the Edge: The Bizarre Double Life of Dr. William Stewart Halsted. New York: Kaplan Publishing, 2010.
Sakorafas, G. H. “Breast Cancer Surgery—Historical Evolution, Current Status and Future Perspectives.” Acta Oncologica 40, no. 1 (2001): 5–18.
Strain, Daniel. “Crushing Cancer’s Defenses: Vaccine Approval Offers Hope While Other Armies Muster.” Science News 179, no. 10 (2011): 20–23. www.jstor.org/stable/41332337.
Teng, Michele W. L., et al. “From Mice to Humans: Developments in Cancer Immunoediting.” Journal of Clinical Investigation 125, no. 9 (2015): 3338–3346.
Tilney, Nicholas L. Invasion of the Body: Revolutions in Surgery. Cambridge, MA: Harvard University Press, 2011.
Villa, Nancy Y., et al. “Therapeutics for Graft-versus-Host Disease: From Conventional Therapies to Novel Virotherapeutic Strategies.” Viruses 8, no. 3 (2016): 85.
CHAPTER 3: CANCERLAND
Ward, R. M. “The Criminal Corpse, Anatomists and the Criminal Law: Parliamentary Attempts to Extend the Dissection of Offenders in Late Eighteenth-Century England.” Journal of British Studies 54, no. 1 (2015): 63–87. doi:10.1017/jbr.2014.167.
“A Failure Led to Drug Against AIDS.” New York Times. September 20, 1986. http://www.nytimes.com/1986/09/20/us/a-failure-led-to-drug-against-aids.html.
Albritton, Lorraine, Lena Tseng, David Scadden, and James M. Cunningham. “A Putative Murine Ecotropic Retrovirus Receptor Gene Encodes a Multiple Membrane-Spanning Protein and Confers Susceptibility to Virus Infection.” Cell 57, no. 4 (1989): 659–666. doi:10.1016/0092-8674(89)90134-7.
Chapple, A., et al. “Stigma, Shame, and Blame Experienced by Patients with Lung Cancer: Qualitative Study.” British Medical Journal 328, no. 7454 (2004): 1470–1473. http://www.jstor.org/stable/41708038.
de la Morena, M. T., and R. A. Gatti. “A History of Bone Marrow Transplantation.” Hematology/Oncology Clinics of North America 25, no. 1 (2011): 1–15. doi:10.1016/j.hoc.2010.11.001.
Engel, Jonathan. The Epidemic: A Global History of AIDS. Washington, D.C.: Smithsonian Press, 2006.
Goodman, Jordan, and Vivien Walsh. The Story of Taxol. Cambridge, UK: Cambridge University Press, 2001.
Greenberg, Daniel S. Science for Sale. Chicago: University of Chicago Press, 2008. 73–80.
“GSS General Social Survey.” NORC at the University of Chicago. http://gss.norc.org.
Hamburg, N. “Emil ‘Tom’ Frei III.” British Medical Journal 347, no. 7920 (2013): 26.
Holland, James F., and Emil Frei III, eds. Cancer Medicine. Philadelphia: Lea & Febiger, 1973.
Kolata, Gina, and Kurt Eichenwald. “Hope for Sale: A Special Report; Business Thrives on Unproven Care, Leaving Science Behind.” New York Times, October 3, 1999. http://www.nytimes.com/1999/10/03/us/hope-for-sale-special-report-business-thrives-unproven-care-leaving-science.html.
Kuhn, Thomas. The Structure of Scientific Revolutions. Chicago: University of Chicago Press, 1962.
“Medicines from Nature.” Harvard T. H. Chan School of Public Health. http://www.chgeharvard.org/topic/medicines-nature.
Newman, D. J., and G. M. Cragg. “Natural Products as Sources of New Drugs over the 30 Years from 1981 to 2010.” Journal of Natural Products 75, no. 3 (2012): 311–335.
Pavlů, Jiří, Richard M. Szydlo, John M. Goldman, and Jane F. Apperley. “Three Decades of Transplantation for Chronic Myeloid Leukemia: What Have We Learned?” Blood 117 (2011): 755–763. https://doi.org/10.1182/blood-2010-08-301341.
Rettig, Richard A., et al. False Hope: Bone Marrow Transplantation for Breast Cancer. New York: Oxford University Press, 2007. 28–29.
Roush, W. “Dana-Farber Death Sends a Warning to Research Hospitals.” Science 269, no. 5222 (1995): 295–296.
Scadden, D. T., Fuller, R., and J. M. Canningham. “Human cells infected with retrovirus vectors acquire an endogenous murine provirus.” Journal of Virology 64, no. 1 (1990): 407–427.
Sibbald, B. “Death but One Unintended Consequence of Gene-Therapy Trial.” Canadian Medical Association Journal 164, no. 11 (2001): 1612.
“Technology Transfer: NIH–Private Sector Partnership in the Development of Taxol.” Washington, D.C.: Government Accounting Office, June 2003.
Yu, Nancy, Zachary Helms, and Peter Bach. “R&D Costs for Pharmaceutical Companies Do Not Explain Elevated U.S. Drug Prices.” Health Affairs, March 7, 2017.
CHAPTER 4: CHEMICALS IN CONVERSATION
Berardi, A. C., Wang, A., Levine, J. D., Lopez, P., and D. T. Scadden. “Functional isolation and characterization of human hematopoietic stem cells.” Science 267, no. 5194 (1995): 104–108.
Berman, Mark, and Elliot Lander. The Stem Cell Revolution. Bloomington, IN: AuthorHouse, 2015.
Bonnicksen, Andrea L. In Vitro Fertilization: Building Policy from Laboratories to Legislatures. New York: Columbia University Press, 1989.
Collins, Nick. “Sir John Gurdon, Nobel Prize Winner, Was ‘Too Stupid’ for Science at School.” Telegraph, October 8, 2012. http://www.telegraph.co.uk/news/science/science-news/9594351/Sir-John-Gurdon-Nobel-Prize-winner-was-too-stupid-for-science-at-school.html.
Davis, Rebecca, and Joe Palca. “A Scientist’s Dream Fulfilled: Harnessing the Immune System to Fight Cancer.” NPR. June 9, 2016. http://www.npr.org/sections/health-shots/2016/06/09/480435066/a-scientists-dream-fulfilled-harnessing-the-immune-system-to-fight-cancer.
Dick, J. “Breast Cancer Stem Cells Revealed.” Proceedings of the National Academy of Sciences of the United States of America 100, no. 7 (2003): 3547–3549.
Grady, Denise. “They Got Breast Implants, Then a Rare Cancer.” New York Times, May 15, 2017.
Jacobsen, Eric. “Anaplastic Large-Cell Lymphoma, T-/Null-Cell Type.” Oncologist 11, no. 7 (2006): 837–840. http://theoncologist.alphamedpress.org/content/11/7/831.full.
McElheny, Victor K. Drawing the Map of Life: Inside the Human Genome Project. New York: Basic Books, 2010.
Shen, H., et al. “CXCR4-desensitization is associated with tissue localization of hematopoietic progenitor cells.” Journal of Immunology, 166, no. 8 (2001): 5027–5033.
Venter, J. Craig. “Taking Genomics into the Environment.” BioScience 56, no. 3 (2006): 197–201. doi:10.1641/0006-3568(2006)056[0197:jcvtgi]2.0.co;2.
Wade, Nicholas. “Genome Analysis Show
s Humans Survive on Low Number of Genes.” New York Times, February 11, 2001.
Yanai, Itai, and Martin Lercher. The Society of Genes. Cambridge, MA: Harvard University Press, 2016.
CHAPTER 5: STEM CELLS AND A RENEWABLE YOU
Carnes, Bruce A., and S. Jay Olshansky. The Quest for Immortality: Science at the Frontiers of Aging. New York: W. W. Norton, 2002.
Druker, B. J. “Janet Rowley (1925–2013).” Nature 505, no. 7484 (2014): 484.
Grens, Kerry. “Amy Wagers: Setting the Record Straight.” Scientist, January 1, 2008. http://www.the-scientist.com/?articles.view/articleNo/25891/title/Amy-Wagers—Setting-the-record-straight/.
Lawler, A. “Steering Harvard toward Collaborative Science.” Science 321, no. 5886 (2008): 190–192.
Lin, H., M. Otsu, and H. Nakauchi. “Stem Cell Therapy: An Exercise in Patience and Prudence.” Philosophical Transactions of the Royal Society B: Biological Sciences 368, no. 1609 (2013): 1–14.
Maehr, R., S. Chen, M. Snitow, T. Ludwig, L. Yagasaki, R. Goland, R. Leibel, and D. Melton. “Generation of Pluripotent Stem Cells from Patients with Type 1 Diabetes.” Proceedings of the National Academy of Sciences of the United States of America 106, no. 37 (2009): 15768–15773.
Marx, J. “Cancer Fighter’s Modus Operandi Revealed.” Science 289, no. 5486 (2000): 1857–1859.
Melton, D., and H. Lodish. “Stem Cell Challenges in Biology and Public Policy.” Bulletin of the American Academy of Arts and Sciences 60, no. 4 (2007): 6–12.
Sinatra, Roberta, Dashun Wang, Pierre Deville, Chaoming Song, and Albert-László Barabási. “Quantifying the Evolution of Individual Scientific Impact.” Science 354, no. 6312 (2016). http://science.sciencemag.org/content/354/6312/aaf5239.
Cancerland Page 30