Survival of the Sickest: A Medical Maverick Discovers Why We Need Disease - Sharon Moalem (2007)

NOTES

Much of the scientific foundation of this book was drawn from my research and that of my collaborators. I have also made liberal use of the work of other scientists, including unpublished research and personal interviews. I hope that the notes below will give you a detailed understanding of the sources, and also provide a launching point for you to find more information about the topics discussed.

INTRODUCTION

my grandfather and me

Ann McIlroy, “Teenager Sharon Moalem Suspected His Grandfather’s Alzheimer’s Was Linked to a Buildup of Iron in His Brain. Years Later, He Proved It,” Globe and Mail, January 31, 2004.

checking for hemochromatosis

The blood tests mentioned in the introduction as a screen for hemochromatosis include the following: total iron binding capacity (TIBC), serum iron, ferritin, and % transferrin saturation. There is also a commercial genetic test available (these can be quite expensive) for the presence of hemochromatosis mutations, but I would not recommend having the test done until there is robust legislation that protects individuals from genetic discrimination.

evolution and medicine

E. R. Stiehm. 2006. Disease versus disease: how one disease may ameliorate another. Pediatrics 117(1):184–191; Randolph M. Nesse and George C. Williams, “Evolution and the Origins of Disease,” scientific American, November 1998; R. M. Nesse. 2001. On the difficulty of defining disease: a Darwinian perspective. Med Health Care Philos 4(1):37–46; E. E. Harris and A. A. Malyango. 2005. Evolutionary explanations in medical and health profession courses: are you answering your students’ “why” questions? BMC Med Educ 5(1):16.

you are not alone

S. R. Gill, M. Pop, R. T. Deboy, et al. 2006. Metagenomic analysis of the human distal gut microbiome. Science 312(5778):1355–1359.

DNA isn’t destiny

See pages 183–198 in Lenny Moss, What Genes Can’t Do (Cambridge, MA: MIT Press, 2003); pages 8–47 in Michael Morange, The Misunderstood Gene (Cambridge, MA: Harvard University Press, 2001); H. Pearson. 2006. Genetics: what is a gene? Nature 441(7092):398–401.

CHAPTER I: IRONING IT OUT

Aran Gordon and hemochromatosis

Kathleen Johnston Jarboe, “Baltimore Business Executive Runs for His Life and Lives of Others,” The Daily Record, April 22, 2005. For a good resource book on hemochromatosis see C. D. Garrison, Iron Disorders Institute, The Iron Disorders Institute Guide to Hemochromatosis (Nashville, TN: Cumberland House, 2001). To watch an NBC news interview with Aran visit www.iron disorders.org/Aran/.

the Geritol Solution

F. M. Morel and N. M. Price. 2003. The biogeochemical cycles of trace metals in the oceans. Science 300(5621):944–947; D. J. Erickson III and J. L. Hernandez. 2003. Atmospheric iron delivery and surface ocean biological activity in the Southern Ocean and Patagonian region. GeoPhys Res Lett 30(12):1609–1612; J. H. Martin, K. H. Coale, K. S. Johnson, et al. 2002. Testing the iron hypothesis in ecosystems of the equatorial Pacific Ocean. Nature 371:123–129; Richard Monastersky, “Iron versus the Greenhouse,” Science News, September 30, 1995; Charles Graeber, “Dumping Iron,” Wired, November 2000.

Eugene D. Weinberg and his lifelong infatuation with iron

To get it directly from the source see E. D. Weinberg and C. D. Garrison, Exposing the Hidden Dangers of Iron: What Every Medical Professional Should Know about the Impact of Iron on the Disease Process (Nashville, TN: Cumberland House, 2004).

bubonic plague

N. E. Cantor, In the Wake of the Plague: The Black Death and the World It Made (New York: Perennial/HarperCollins, 2002); J. Kelly, The Great Mortality: An Intimate History of the Black Death, the Most Devastating Plague of All Time (New York: HarperCollins, 2005).

Alas! Our ships enter the port

Gabriele de’Mussi, Istoria de morbo siue mortalitate que fuit de 1348, page 76 in G. Deaux, The Black Death, 1347 (New York: Weybright and Talley, 1969). For more about the plague as literary motif see www.brown.edu/Departments/ Italian_Studies/dweb/plague/perspectives/de_mussi.shtml.

Passover and the plague

For an intriguing account of the possible connections between the Jewish observances of Passover and plague prevention see M. J. Blaser. 1998. Passover and plague. Perspect Biol Med 41(2):243–256.

Father abandoned child

Angelo di Tura, Seina Chronicle, 1354, pages 13–14 in W. M. Bowsky, The Black Death: A Turning Point in History (New York: Holt, 1971).

“Iron status mirror [edmortality”

In some of the most recent outbreaks of plague men and women seemed to be equally affected. This could possibly be attributed to our diets’ being more iron “rich” as a result of fortification of grains and processed foods. See S. R. Ell. 1985. Iron in two seventeenth-century plague epidemics. J Interdiscip Hist 15(3):445–457, which provides more on the epidemiology of bubonic plague and how young men seem to have been most susceptible.

plague in London

For a great article by Graham Twigg with maps of parishes during the plague in London see www.history.ac.uk/cmh/epitwig.html, originally published as Plague in London: Spatial and Temporal Aspects of Mortality, in Epidemic Disease in London, ed. J. A. I. Champion, Centre for Metropolitan History Working Papers Series, No. 1 (1993).

hemochromatosis and the plague

For the original paper describing the proposed connection between hemochromatosis and the plague see S. Moalem, M. E. Percy, T. P. Kruck, and R. R. Gelbart. 2002. Epidemic pathogenic selection: an explanation for hereditary hemochromatosis? Med Hypotheses 59(3):325–329. For more information on the importance of iron in bacterial infections see S. Moalem, E. D. Weinberg, and M. E. Percy. 2004. Hemochromatosis and the enigma of misplaced iron: implications for infectious disease and survival. Biometals 17(2):135–139.

the Bruce Lees of the immune system

Researchers have yet to test the fighting ability of macrophages of people who have hemochromatosis directly. Yet in a recent study researchers found that the microbe that causes tuberculosis (Mycobacterium tuberculosis) had a much more difficult time acquiring iron from cells of people who had hemochromatosis. Since most pathogenic bacteria (like Yersinia pestis, which is thought to have caused the bubonic plagues) and fungi depend upon iron for their infectivity, it is thought that this may in fact be the advantage that led hemochromatosis mutations to become so prevalent in Western Europe. The following reference is for the experiments mentioned: O. Olakanmi, L.S. Schlesinger, and B. E. Britigan. 2006. Hereditary hemochromatosis results in decreased iron acquisition and growth by Mycobacterium tuberculosis with human macrophages. J Leokoc Biol (Epub October 12, 2006, ahead of print); O. Olakanmi, L. S. Schlesinger, A. Ahmed, and B. E. Britigan. 2002. Intraphagosomal Mycobacterium tuberculosis acquires iron from both extracellular transferrin and intracellular iron pools: impact of interferon-gamma and hemochromatosis. J Biol Chem 277(51):49727–49734. Don’t think for one second that people who have hemochromatosis are completely immune to infectious predation. There is one organism in particular that can wreak havoc on those with iron overload, Vibrio vulnificus. This organism is usually found in seafood and seawater, and it has a unique way of acquiring iron that makes people who have hemochromatosis highly susceptible to infection. For more on Vibrio vulnificus see J. J. Bullen, P. B. Spalding, C. G. Ward, and J. M. Gutteridge. 1991. Hemochromatosis, iron and septicemia caused by Vibrio vulnificus. Arch Intern Med 151(8):1606–1609. For more fun vibrio facts see the following two websites of the CDC and FDA: www.cdc.gov/ncidod/dbmd/diseaseinfo/ vibriovulnificus_g.htm and www.cfsan.fda.gov/~mow/chap10.html.

the Vikings and hemochromatosis

For more information on the debate regarding the origins of hemochromatosis see N. Milman and P. Pedersen. 2003. Evidence that the Cys282Tyr mutation of the HFE gene originated from a population in Southern Scandinavia and spread with the Vikings. Clin Genet 64(1):36–47; A. Pietrangelo. 2004. Hereditary hemochromatosis—a new look at an old disease. N Engl J Med 350(23):2383–2397; G. Lucotte and F. Dieterlen. 2003. A European allele map of the C282Y mutation of hemochromatosis: Celtic versus Viking origin of the mutation? Blood Cells Mol Dis 31(2):262–267.

on the history of bloodletting

For a fun read on the science behind the ancient practice of bloodletting see chapter 6, “A Bloody Good Remedy,” in R. S. Root-Bernstein and M. Root-Bernstein, Honey, Mud, Maggots, and Other Medical Marvels: The Science behind Folk Remedies and Old Wives’ Tales (Boston: Houghton Mifflin, 1997); also see R. J. Weinberg, S. R. Ell, and E. D. Weinberg. 1986. Bloodletting, iron homeostasis, and human health. Med Hypotheses 21(4):441–443. For a paper covering a thorough history of bloodletting see G. R. Seigworth, 1980. Bloodletting over the centuries. N Y State J Med 80(13):2022–2028. To view a surgeon’s bloodletting kit from the U.S. War of Independence see http:// americanhistory.si.edu/militaryhistory/exhibition/flash.html?path=1.3.r_70.

To learn more about bloodletting and fever reduction see N. W. Kasting, 1990. A rationale for centuries of therapeutic bloodletting: antipyretic therapy for febrile diseases. Perspect Biol Med 33(4):509–516.

iron, infection, Maori babies, and botulism

M. J. Murray, A. B. Murray, M. B. Murray, and C. J. Murray. 1978. The adverse effect of iron repletion on the course of certain infections. Br Med J 2(6145):1113–1115; R. J. Cantwell. 1972. Iron deficiency anemia of infancy: some clinical principles illustrated by the response of Maori infants to neonatal parenteral iron administration. Clin Pediatr (Phila) 11(8):443–449; S. S. Arnon, K. Damus, B. Thompson, et al. 1982. Protective role of human milk against sudden death from infant botulism. J Pediatr 100(4): 568–573.

CHAPTER II: A SPOONFUL OF SUGAR HELPS THE TEMPERATURE GO DOWN

How many people have diabetes?

For an updated account of the worldwide prevalence of diabetes see the World Health Organization website at www.who.int.

Chinese medicine

For a historical view of ancient Chinese medical practices and beliefs see J. Veith and Ti Huang, The Yellow Emperor’s Classic of Internal Medicine (Berkeley: University of California Press, 1966); for a current overview of how ancient Chinese medical practices continue in China see V. Scheid, Chinese Medicine in Contemporary China: Plurality and Synthesis (Durham, NC: Duke University Press, 2002).

Pima Indians

For more information on the Pima Indians of the southwestern United States see diabetes.niddk.nih.gov/dm/pubs/pima/obesity/obesity.htm. For a personal account of the state of health of Pima Indians see G. P. Nabhan, Why Some Like It Hot: Food, Genes, and Cultural Diversity (Washington, DC: Island Press/Shearwater Books, 2004).

climate change and global warming

Two good books on the subject: B. M. Fagan, The Little Ice Age: How Climate Made History, 1300–1850 (New York: Basic Books, 2000); T. F. Flannery, The Weather Makers: How Man Is Changing the Climate and What It Means for Life on Earth (New York: Atlantic Monthly Press, 2005).

Younger Dryas

S. Bondevik, J. Mangerud, H. H. Birks, et al. 2006. Changes in North Atlantic radiocarbon reservoir ages during the Allerod and Younger Dryas. Science 312(5779):1514–1517; National Research Council (U.S.), Committee on Abrupt Climate Change, Abrupt Climate Change: Inevitable Surprises (Washington, DC: National Academies Press, 2002); L. Tarasov and W. R. Peltier. 2005. Arctic freshwater forcing of the Younger Dryas cold reversal. Nature435(7042):662–665; T. Correge, M. K. Gagan, J. W. Beck, et al. 2004. Inter-decadal variation in the extent of South Pacific tropical waters during the Younger Dryas event. Nature 428(6986):927–929; C. Singer, J. Shulmeister, and B. McLea. 1998. Evidence against a significant Younger Dryas cooling event in New Zealand. Science 281(5378):812–814; Richard B. Alley, “Abrupt Climate Change,” scientific American, November 2004.

Through most of the 20th century

S. R. Weart, The Discovery of Global Warming (Cambridge, MA: Harvard University Press, 2003). To read about the implications of a breakdown in the Atlantic conveyer see Fred Pearce, “Faltering Currents Trigger Freeze Fear,” New Scientist, December 3, 2005.

on ice cores

R. B. Alley, The Two-Mile Time Machine: Ice Cores, Abrupt Climate Change, and Our Future (Princeton, NJ: Princeton University Press, 2000).

for a peek at Europeans: before and after the Younger Dryas

C. Gamble, W. Davies, P. Pettitt, and M. Richards. 2004. Climate change and evolving human diversity in Europe during the last glacial. Philos Trans R Soc Lond B Biol Sci 359(1442):243–253; discussion 253–254.

baseball legend Ted Williams

Tom Verducci, “New Details Fuel Controversy Surrounding Williams’ Remains,” Sports Illustrated, August 12, 2003. If you’d like to join the “Save Ted Williams” club see www.saveted.net.

Alcor Life Extension cryonics lab

If you’re interested in the latest and greatest in cryogenics at Alcor see www.alcor.org.

brown fat

See the following research papers for the magic of brown fat and cold tolerance: B. Cannon and J. Nedergaard. 2004. Brown adipose tissue: function and physiological significance. Physiol Rev 84(1):277–359; A. L. Vallerand, J. Zamecnik, and I. Jacobs. 1995. Plasma glucose turnover during cold stress in humans. J Appl Physiol 78(4):1296–1302; J. Watanabe, S. Kanamura, H. Tokunaga, et al. 1987. significance of increase in glucose 6-phosphatase activity in brown adipose cells of cold-exposed and starved mice. Anat Rec 219(1):39–44; A. L. Vallerand, F. Perusse, and L. J. Bukowiecki. 1990. Stimulatory effects of cold exposure and cold acclimation on glucose uptake in rat peripheral tissues. Am J Physiol 259(5, Pt 2):R1043–R1049; A. Porras, S. Zuluaga, A. Valladares, et al. 2003. Long-term treatment with insulin induces apoptosis in brown adipocytes: role of oxidative stress. Endocrinology144(12):5390–5401.

cold diuresis

For the controversy, history, and science behind urinating when you’re cold, and the Sunderland quote, see pages 161–176 in B. M. Marriott and S. J. Carlson, Institute of Medicine (U.S.), Committee on Military Nutrition Research, Nutritional Needs in Cold and in High-Altitude Environments: Applications for Military Personnel in Field Operations (Washington, DC: National Academies Press, 1996).

the frogsicle (Rana sylvatica)

Elizabeth Svoboda, “Waking from a Dead Sleep,” Discover, February 2005; K. B. Storey and J. M. Storey. 1999. Lifestyles of the cold and frozen. The Sciences 39(3), 32–37; David A. Fahrenthold, “Looking to Frozen Frogs for Clues to Improve Human Medicine,” Seattle Times, December 15, 2004. For more information on applications of cold tolerance to medical practice see Cold Cures, by Dr. Boris Rubinsky, at www.pbs.org/wgbh/nova/sciencenow/ 3209/05-cures.html.

diabetes and evolution

Sandra Blakeslee, “New Theory Places Origin of Diabetes in an Age of Icy Hardships,” New York Times, May 17, 2005. For the original paper describing the proposed diabetes–cold tolerance link see S. Moalem, K. B. Storey, M. E. Percy, et al. 2005. The sweet thing about Type 1 diabetes: a cryoprotective evolutionary adaptation. Med Hypotheses 65(1):8–16. For more reading on the subject of climate change and human evolution see W. H. Calvin, A Brain for All Seasons: Human Evolution and Abrupt Climate Change (Chicago: University of Chicago Press, 2002).

fibrinogen and the cold

R. C. Hermida, C. Calvo, D. E. Ayala, et al. 2003. Seasonal variation of fibrinogen in dipper and nondipper hypertensive patients. Circulation 108(9):1101–1106; V. L. Crawford, S. E. McNerlan, and R. W. Stout. 2003. Seasonal changes in platelets, fibrinogen and factor VII in elderly people. Age Ageing 32(6):661–665; R. W. Stout and V. Crawford. 1991. Seasonal variations in fibrinogen concentrations among elderly people. Lancet 338(8758):9–13.

American veterans with diabetes

This very large study tracked 285,705 American veterans for almost two years looking at blood levels of hemoglobin A1c, which is clinically used as a marker for glucose levels over an extended period of time. The hemoglobin A1c test is based on the behavior of glucose, which binds to hemoglobin irreversibly (once glucose is bound, hemoglobin is then called glycated hemoglobin or hemoglobin A1c). Since red blood cells that house hemoglobin hang on for at least two to three months before being replaced, measuring glycated hemoglobin gives clinicians and scientists a much better window into how well the diabetes is being controlled in the individual over time. For the study mentioned in the chapter see C. L. Tseng, M. Brimacombe, M. Xie, et al. 2005. Seasonal patterns in monthly hemoglobin A1c values. Am J Epidemiol 161(6):565–574.

CHAPTER III: THE CHOLESTEROL ALSO RISES

sunlight and vitamin D

Ingfei Chen, “Sunlight, a Cancer Protector in the Guise of a Villain?” New York Times, August 6, 2002; M. F. Holic. 2004. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 80(6 Suppl):1678S–1688S; J. M. Pettifor, G. P. Moodley, F. S. Hough, et al. 1996. The effect of season and latitude on in vitro vitamin D formation by sunlight in South Africa. S Afr Med J 86(10):1270–1272; Anne Marie Owens, “Second-Guessing the Big Cover-up,” National Post, February 14, 2005; V. Tangpricha, A. Turner, C. Spina, et al. 2004. Tanning is associated with optimal vitamin D status (serum 25-hydroxyvitamin D concentration) and higher bone mineral density. Am J Clin Nutr 80(6):1645–1649; P. T. Liu, S. Stenger, H. Li, et al. 2006. Toll-like receptor triggering of a vitamin D–mediated human antimicrobial response. Science311(5768):1770–1773; A. Zitterman. 2003. Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr 89(5):552–572; R. Roelandts. 2002. The history of phototherapy: something new under the sun? J Am Acad Dermatol 46(6):926–930.

seasonal variation in cholesterol levels

I. S. Ockene, D. E. Chiriboga, E. J. Stanek III, et al. 2004. Seasonal variation in serum cholesterol levels: treatment implications and possible mechanisms. Arch Intern Med 164(8):863–870; M. Bluher, B. Hentschel, F. Rassoul, and V. Richter. 2001. influence of dietary intake and physical activity on annual rhythm of cholesterol concentrations. Chronobial Int 18(3):541–557.

Crohn’s and suntanning

P. Koutkia, Z. Lu, T. C. Chen, and M. F. Holick. 2001. Treatment of vitamin D deficiency due to Crohn’s disease with tanning bed ultraviolet B radiation. Gastroenterology 121(6):1485–1488.

folic acid and folate

L. D. Botto, A. Lisi, E. Robert-Gnansia, et al. 2005. International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working? BMJ 330(7491):571; D. B. Shurtleff. 2004. Epidemiology of neural tube defects and folic acid. Cerebrospinal Fluid Res 1(1):5; B. Kamen. 1997. Folate and antifolate pharmacology. Semin Oncol 24(5 Suppl 18):S18-30–S18-39. For the report mentioned in the chapter about three mothers who gave birth to children who had neural tube defects after they had tanned during pregnancy see P. Lapunzina. 1996. Ultraviolet light–related neural tube defects? Am J Med Genet 67(1):106.

skin color

N. G. Jablonski and G. Chaplin. 2000. The evolution of human skin coloration. J Hum Evol 39(1):57–106; H. Y. Thong, S. H. Jee, C. C. Sun, and R. E. Boissy. 2003. The patterns of melanosome distribution in keratinocytes of human skin as one determining factor of skin colour. Br J Dermatol 149(3):498–505; R. L. Lamason, M. A. Mohideen, J. R. Mest, et al. 2005. SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science 310(5755):1782–1786; A. J. Th ody, E. M. Higgins, K. Wakamatsu, et al. 1991. Pheomelanin as well as eumelanin is present in human epidermis. J Invest Dermatol 97(2):340–344; Saadia Iqbal, “A New Light on Skin Color,” National Geographic Magazine, November 2002; Nina G. Jablonski and George Chaplin, “Skin Deep,” scientific American, October 2002; Adrian Barnett, “Fair Enough,” New Scientist, October 12, 2002.

skin cancer

For facts and figures regarding the many different types of skin cancers see the following excellent website: www.cancer.org/docroot/PED/content/ped_7_ 1_What_You_Need_To_Know_About_Skin_Cancer.asp. See also pages 57–72 in R. Ehrlich, Nine Crazy Ideas in Science: A Few Might Even Be True (Princeton, NJ: Princeton University Press, 2001).

red hair

P. Valverde, E. Healy, I. Jackson, et al. 1995. Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nat Genet 11(3):328–330; Robin L. Flanigan, “Will Rare Redheads Be Extinct by 2100?” Seattle Times, May 9, 2005; T. Ha and J. L. Rees. 2001. Melanocortin 1 receptor: what’s red got to do with it? J Am Acad Dermatol 45(6):961–964.

cod liver oil

See pages 10–11 in the wonderful book, R. S. Root-Bernstein and M. Root-Bernstein, Honey, Mud, Maggots, and Other Medical Marvels: The Science Behind Folk Remedies and Old Wives’ Tales (Boston: Houghton Mifflin, 1997); K. Rajakumar. 2003. Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective. Pediatrics 112(2):e132–e135; M. Brustad, T. Sandanger, L. Aksnes, and E. Lund. 2004. Vitamin D status in a rural population of northern Norway with high fish liver consumption. Public Health Nutr 7(6):783–789; D. J. Holub and B. J. Holub. 2004. Omega-3 fatty acids from fish oils and cardiovascular disease. Mol Cell Biochem 263(1–2):217–225.

the benefits of ACHOO syndrome

H. C. Everett. 1964. Sneezing in response to light. Neurology 14:483–490. For more see R. Smith. 1990. Photic sneezes. Br J Ophthalmol 74(12):705; S. J. Peroutka and L. A. Peroutka. 1984. Autosomal dominant transmission of the “photic sneeze reflex.” N Engl J Med 310(9):599–600; J. M. Forrester. 1985. Sneezing on exposure to bright light as an inherited response. Hum Hered 35(2):113–114; E. W. Benbow. 1991. Practical hazards of photic sneezing. Br J Ophthalmol 75(7):447.

Asian flush: the genetics of alcohol consumption

T. L. Wall, S. M. Horn, M. L. Johnson, et al. 2000. Hangover symptoms in Asian Americans with variations in the aldehyde dehydrogenase (ALDH2) gene. J Stud Alcohol 61(1):13–17; M. Yokoyama, A. Yokoyama, T. Yokoyama, et al. 2005. Hangover susceptibility in relation to aldehyde dehydrogenase-2 genotype, alcohol flushing, and mean corpuscular volume in Japanese workers. Alcohol Clin Exp Res 29(7):1165–1171; K. A. Veverka, K. L. Johnson, D. C. Mays, et al. 1997. Inhibition of aldehyde dehydrogenase by disulfiram and its metabolite methyl diethylthiocarbamoyl-sulfoxide. Biochem Pharmacol 53(4):511–518; Janna Chan, “Asian Flush: The Silent Killer,” AsianAvenue.com, November 18, 2004.

the Cohan gene

See pages 140–165 in M. Z. Wahrman, Brave New Judaism: When Science and Scripture Collide (Hanover, NH: University Press of New England for Brandeis University Press, 2002); K. Skorecki, S. Selig, S. Blazer, et al. 1997. Y chromosomes of Jewish priests. Nature 385(6611):32; M. G. Thomas, K. Skorecki, H. Ben-Ami, et al. 1998. Origins of Old Testament priests. Nature 394(6689):138–140. This recent paper challenges the previous findings: A. Zoossmann-Diskin. 2006. Ashkenazi Levites’ “Y modal haplotype” (LMH)—an artificially created phenomenon? Homo 57(1):87–100.

“population clusters”

For more on Dr. Henry Louis Gates see www.pbs.org/wnet/aalives/science_ dna2.html. See also Editorial. 2001. Genes, drugs and race. Nat Genet 29(3):239–240; Emma Daly, “DNA Tells Students They Aren’t Who They Th ought,” New York Times, April 13, 2005; Marek Kohn, “This Racist Undercurrent in the Tide of Genetic Research,” Guardian, January 17, 2006; Richard Willing, “DNA Tests to offer Clues to Suspect’s Race,” USA Today, August 17, 2005.

African slave trade and hypertension

See R. Cooper and C. Rotimi. 1997. Hypertension in blacks. Am J Hypertens 10(7 Pt 1):804–812; M. P. Blaustein and C. E. Grim. 1991. The pathogenesis of hypertension: black-white differences. Cardiovasc Clin 21(3):97–114. For more information regarding “how being black affects your blood pressure” see www.mayoclinic.com/health/high-blood-pressure/HI00067. For more information on the “Middle Passage” see page 33 of N. I. Painter, Creating Black Americans: African-American History and Its Meanings, 1619 to the Present (New York: Oxford University Press, 2006); also see J. Postma, The Atlantic Slave Trade (Gainesville: University Press of Florida, 2005); Harold M. Schmeck Jr., “Study of Chimps Strongly Backs Salt’s Link to High Blood Pressure,” New York Times, October 3, 1995; Richard S. Cooper, Charles N. Rotimi, and Ryk Ward, “The Puzzle of Hypertension in African-Americans,” Scientific American, February 1999. For specific racial/ethnic statistics see the U.S. government’s Office of Minority Health website at www.omhrc.gov.

mortality during the Middle Passage

See pages 43–59 in J. Postma, The Atlantic Slave Trade (Gainesville: University Press of Florida, 2005).

BiDil

Stephanie Saul, “F.D.A. Approves a Heart Drug for African-Americans,” New York Times, June 24, 2005; Kai Wright, “Death by Racism,” Dallas Morning News, June 25, 2006; for more on this controversial drug see www.bidil. com.

fast versus slow drug metabolizers

I. Johansson, E. Lundqvist, L. Bertilsson, et al. 1993. Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultra-rapid metabolism of debrisoquine. Proc Natl Acad Sci U S A 90(24):11825–11829.

multiple copies of genes

For more on this topic see Bob Holms, “Magic Numbers,” New Scientist, April 8, 2006; R. Tubbs, J. Pettay, D. Hicks, et al. 2004. Novel bright field molecular morphology methods for detection of HER2 gene amplification. J Mol Histol 35(6):589–594.

overdosing on cough syrup: the CYP2D6 connection

Y. Gasche, Y. Daali, M. Fathi, et al. 2004. Codeine intoxication associated with ultrarapid CYP2D6 metabolism. N Engl J Med 351(27):2827–2831.

immunity to HIV: CCR5-?32

For more on the total absence of CCR5-?32 in other populations, specifically the Indian population, and the increased risk of HIV infection, see Seema Singh Bangalore, “‘Wrong’ Genes May Raise AIDS Risk for Millions,” New Scientist, April 16, 2005; Julie Clayton, “Beating the Odds,” New Scientist, February 8, 2003; J. Novembre, A. P. Galvani, and M. Slatkin. 2005. The geographic spread of the CCR5-Delta32 HIV-resistance allele. PLoS Biol 3(11): e339.

pharmacogenomics

T. A. Clayton, J. C. Lindon, O. Cloarec, et al. 2006. Pharmaco-metabonomic phenotyping and personalized drug treatment. Nature 440(7087):1073–1077; S. K. Tate and D. B. Goldstein. 2004. Will tomorrow’s medicines work for everyone? Nat Genet 36(11 Suppl):S34–S42; I. Roots, T. Gerloff, C. Meisel, et al. 2004. Pharmacogenetics-based new therapeutic concepts. Drug Metab Rev 36(3–4):617–638; R. E. Cannon. 2006. A discussion of gene-environment interactions: fundamentals of ecogenetics. Environ Health Perspect 114(6):a382; C. G. N. Mascie-Taylor, J. Peters, and S. McGarvey, Society for the Study of Human Biology, The Changing Face of Disease: Implications for Society (Boca Raton, FL: CRC Press, 2004); Jo Whelan, “Where’s the Smart Money Going in Biotech?” New Scientist, June 18, 2005; for more information see the Centers for Disease Control and Prevention website at www.cdc.gov/PCD/ issues/2005/apr/04_0134.htm.

personalized medicine: pharmacogenomics or pharmacogenetics

For a “future model of cancer care,” see the special May 26, 2006, issue of the journal Science 312(5777):1157–1175.

CHAPTER IV: HEY, BUD, CAN YOU DO ME A FAVA?

fava beans aka broad beans

See pages 40–41 in M. Toussaint-Samat, A History of Food (Cambridge, MA: Blackwell Reference, 1993); D. Zohary and M. Hopf, Domestication of Plants in the Old World: The Origin and Spread of Cultivated Plants in West Asia, Europe, and the Nile Valley (New York: Oxford University Press, 2000); J. Golenser, J. Miller, D. T. Spira, et al. 1983. Inhibitory effect of a fava bean component on the in vitro development of Plasmodium falciparum in normal and glucose-6-phosphate dehydrogenase deficient erythrocytes. Blood 61(3): 507–510.

Pythagoras and fava beans

J. Meletis and K. Konstantopoulos. 2004. Favism—from the “avoid fava beans” of Pythagoras to the present. Haema 7(1):17–21.

One should abstain

Quoted in R. Parsons, “The Long History of the Mysterious Fava Bean,” Los Angeles Times, May 29, 1996.

favism

K. Iwai, A. Hirono, H. Matsuoka, et al. 2001. Distribution of glucose 6-phosphate dehydrogenase mutations in Southeast Asia. Hum Genet 108(6):445–449; A. K. Roychoudhury and M. Nei. Human Polymorphic Genes: World Distribution (New York: Oxford University Press, 1988); S. H. Katz and J. Schall. 1979. Fava bean consumption and biocultural evolution. Med Anthro 3:459–476; S. A. Tishkoff, R. Varkonyi, N. Cahinhinan, et al. 2001. Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science 293(5529):455–462.

Korean War and favism

For more on this topic see pages 70–91 in G. P. Nabhan, Why Some Like It Hot: Food, Genes, and Cultural Diversity (Washington, DC: Island Press/ Shearwater Books, 2004); C. F. Ockenhouse, A. Magill, D. Smith, and W. Milhous. 2005. History of U.S. military contributions to the study of malaria. Mil Med 170(4 Suppl):12–16; A. S. Alving, P. E. Carson, C. L. Flanagan, and C. E. Ickes. 1956. Enzymatic deficiency in primaquine-sensitive erythrocytes. Science 124(3220):484–485.

G6PD and malaria

See pages 92–94 in E. Barnes, Diseases and Human Evolution (Albuquerque: University of New Mexico Press, 2005); H. Ginsburg, H. Atamna, G. Shalmiev, et al. 1996. Resistance of glucose-6-phosphate dehydrogenase deficiency to malaria: effects of fava bean hydroxypyrimidine glucosides on Plasmodium falciparum growth in culture and on the phagocytosis of infected cells. Parasitology 113(Pt 1):7–18.

sexy chromosomes

When it comes to sex chromosome numbers there are other possible combinations, including Turner’s syndrome, which results from having only one fully functional X chromosome (X,O), or Klinefelter syndrome, where a male has an extra X chromosome (XXY).

“natural” poisons and protectants in the food we eat

For the original studies see A. Fugh-Berman and F. Kronenberg. 2001. Red clover (Trifolium pratense) for menopausal women: current state of knowledge. Menopause 8(5):333–337; H. W. Bennetts, E. J. Underwood, and F. L. Shier. 1946. A specific breeding problem of sheep on subterranean clover pastures in Western Australia. Aust J Agric Res 22:131–138; S. M. Heinonen, K. Wahala, and H. Adlercreutz. 2004. Identification of urinary metabolites of the red clover isoflavones formononetin and biochanin A in human subjects. J Agric Food Chem 52(22):6802–6809; M. A. Wallig, K. M. Heinz-Taheny, D. L. Epps, and T. Gossman. 2005. Synergy among phytochemicals within crucifers: does it translate into chemoprotection? J Nutr 135(12 Suppl): 2972S–2977S. For more information on “natural” toxins in the foods we eat see the following: K. F. Lampe, M. A. McCann, and American Medical Association, AMA Handbook of Poisonous and Injurious Plants (Chicago: American Medical Association, distributed by Chicago Review Press, 1985); M. Stacewicz-Sapuntzakis and P. E. Bowen. 2005. Role of lycopene and tomato products in prostate health. Biochim Biophys Acta 1740(2):202–205; National Research Council (U.S.), Food Protection Committee, Toxicants Occurring Naturally in Food (Washington, DC: National Academy of Sciences, 1973); D. R. Jacobs Jr. and L. M. Steffen. 2003. Nutrients, foods, and dietary patterns as exposures in research: a framework for food synergy. Am J Clin Nutr 78(3 Suppl):508S–513S; J. M. Kingsbury, Poisonous Plants of the United States and Canada (Englewood Cliff s, NJ: Prentice-Hall, 1964). For cassava toxicity see M. Ernesto, A. P. Cardoso, D. Nicala, et al. 2002. Persistent konzo and cyanogen toxicity from cassava in northern Mozambique. Acta Trop 82(3):357–362; M. L. Mlingi, M. Bokanga, F. P. Kavishe, et al. 1996. Milling reduces the goitrogenic potential of cassava. Int J Food Sci Nutr 47(6):445–454. For chickpea poisons see P. Smirnoff, S. Khalef, Y. Birk, and S. W. Applebaum. 1976. A trypsin and chymotrypsin inhibitor from chick peas (Cicer arietinum). Biochem J 157(3):745–751.

Carl Djerassi and the Pill

For a personal account of the birth of the “Pill” see C. Djerassi, This Man’s Pill: reflections on the 50th Birthday of the Pill (New York: Oxford University Press, 2001) and C. Djerassi, The Pill, Pygmy Chimps, and Degas’ Horse: The Autobiography of Carl Djerassi (New York: Basic Books, 1992).

Indian vetch

Leigh Dayton, “Australia Exports Poisonous ‘Lentils,’” New Scientist, October 3, 1992; for more information see www.cropscience.org.au/icsc2004/ poster/3/2/1/769_vetch.htm.

the deadly nightshade family

J. L. Muller. 1998. Love potions and the ointment of witches: historical aspects of the nightshade alkaloids. J Toxicol Clin Toxicol 36(6):617–627.

Some of them ate plentifully

R. Beverley and L. B. Wright, The History and Present State of Virginia (Charlottesville, VA: Dominion Books, 1968); S. Berkov, R. Zayed, and T. Doncheva. 2006. Alkaloid patterns in some varieties of Datura stramonium. Fitoterapia 77(3):179–182.

the ethnicity of capsaicin

There is considerable variation in the P450 class of enzymes in different ethnic groups, most likely the result of having lived in very different “chemical environments.” This cytochrome system is what is used by the body to process or “detoxify” chemicals including prescription drugs. The following article is important in that it looks at the metabolism of capsaicin, the molecule that puts the fire in hot peppers by cytochrome P450: C. A. Reilly, W. J. Ehlhardt, D. A. Jackson, et al. 2003. Metabolism of capsaicin by cytochrome P450 produces novel dehydrogenated metabolites and decreases cytotoxicity to lung and liver cells. Chem Res Toxicol 16(3):336–349. These differences are also the basis of the proposed future of personalized medicine based on the genes you might have called pharmacogenomics or pharmacogenetics. See P. Gazerani and L. Arendt-Nielsen. 2005. The impact of ethnic differences in response to capsaicin-induced trigeminal sensitization. Pain 117(1–2):223–229.

capsaicin: the spice that can cause neurodegeneration and stomach cancer

A. Mathew, P. Gangadharan, C. Varghese, and M. K. Nair. 2000. Diet and stomach cancer: a case-control study in South India. Eur J Cancer Prev 9(2):89–97; G. Jancso and S. N. Lawson. 1990. Transganglionic degeneration of capsaicin-sensitive C-fiber primary aff erent terminals. Neuroscience 39(2): 501–511; D. H. Wang, W. Wu, and K. J. Lookingland. 2001. Degeneration of capsaicin-sensitive sensory nerves leads to increased salt sensitivity through enhancement of sympathoexcitatory response. Hypertension 37(2 Pt 2):440–443.

There are many articles regarding the benefits of capsaicin; these are just a few: E. Pospisilova and J. Palecek. 2006. Postoperative pain behavior in rats is reduced after single high-concentration capsaicin application. Pain [Epub June 21, 2006, ahead of print]; A. L. Mounsey, L. G. Matthew, and D. C. Slawson. 2005. Herpes zoster and postherpetic neuralgia: prevention and management. Am Fam Physician 72(6):1075–1080; Mary Ann Ryan, “Capsaicin Chemistry Is Hot, Hot, Hot!” American Chemical Society, March 24, 2003, available online at www.chemistry.org/portal/a/c/s/1/feature_ent.html?id =b90b964c5ade11d7e3d26ed9fe800100.

bitterness

N. Soranzo, B. Bufe, P. C. Sabeti, et al. 2005. Positive selection on a high-sensitivity allele of the human bitter-taste receptor TAS2R16. Curr Biol 15(14):1257–1265; B. Bufe, T. Hofmann, D. Krautwurst, et al. 2002. The human TAS2R16 receptor mediates bitter taste in response to beta-glucopyranosides. Nat Genet 32(3):397–401.

supertasters

A. Drewnowski, S. A. Henderson, A. B. Shore, and A. Barratt-Fornell. 1997. Nontasters, tasters, and supertasters of 6-n-propylthiouracil (PROP) and hedonic response to sweet. Physiol Behav 62(3):649–655; G. L. Goldstein, H. Daun, and B. J. Tepper. 2005. Adiposity in middle-aged women is associated with genetic taste blindness to 6-n-propylthiouracil. Obes Res 13(6):1017–1023. See pages 118–123 in G. P. Nabhan, Why Some Like It Hot: Food, Genes, and Cultural Diversity (Washington, DC: Island Press/Shearwater Books, 2004).

potato late blight (Phytopthora infestans)

For a great microscopic image of potato late blight see http://helios.bto.ed.ac.uk/bto/microbes/blight.htm.

sensitivity to psoralen

The following paper is about a sixty-five-year-old woman who had a serious dermatological reaction after she ate a large quantity of celery root (Apium graveolens) and visited a tanning salon: B. Ljunggren. 1990. Severe phototoxic burn following celery ingestion. Arch Dermatol 126(10):1334–1336. Also see L. Wang, B. Sterling, and P. Don. 2002. Berloque dermatitis induced by “Florida water.” Cutis 70(1):29–30; Institute of Medicine (U.S.). Committee on Identifying and Assessing Unintended effects of Genetically Engineered Foods on Human Health, Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health effects (Washington, DC: National Academies Press, 2004), 44.

G6PD and malaria

A. Yoshida and E. F. Roth Jr. 1987. Glucose-6-phosphate dehydrogenase of malaria parasite Plasmodium falciparum. Blood 69(5):1528–1530; C. Ruwende and A. Hill. 1998. Glucose-6-phosphate dehydrogenase deficiency and malaria. J Mol Med 76(8):581–588; F. P. Mockenhaupt, J. Mandelkow, H. Till, et al. 2003. Reduced prevalence of Plasmodium falciparum infection and of concomitant anaemia in pregnant women with heterozygous G6PD deficiency. Trop Med Int Health 8(2):118–124; C. Ruwende, S. C. Khoo, R. W. Snow, et al. 1995. Natural selection of hemi-and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature 376(6537):246–249.

malaria

See pages 69–83 in E. Barnes, Diseases and Human Evolution (Albuquerque: University of New Mexico Press, 2005); and pages 715–722 of K. J. Ryan, C. G. Ray, and J. C. Sherris, Sherris Medical Microbiology: An Introduction to Infectious Diseases (New York: McGraw-Hill, 2004). For a wonderfully rich history of malaria see K. F. Kiple, The Cambridge World History of Human Disease (New York: Cambridge University Press, 1993). For an excellent account of the problems of malaria and pregnancy see the World Health Organization’s website www.who.int/features/2003/04b/en/. For a review of the worldwide malarial distribution and risks for travelers including maps see www.ncid.cdc.gov/travel/yb/utils/ybGet.asp?section=dis&obj=index.htm.

Hippocrates

For a free online copy of Hippocrates’ On Airs, Waters, and Places see the Massachusetts Institute of Technology (MIT) website at classics.mit.edu/ Hippocrates/airwatpl.html.

on miasma

M. Susser. 2001. Glossary: causality in public health science. Epidemiol Community Health 55:376–378.

air-conditioning and malaria

For a more in-depth account of this fascinating story see James Burke, “Cool Stuff,” scientific American, July 1997; also see chapter 10 in J. Burke, Connections (Boston: Little, Brown, 1995).

J. B. S. Haldane

J. Lederberg. 1999. J. B. S. Haldane (1949) on infectious disease and evolution. Genetics 153(1):1–3. For a biographical account of Haldane and his ideas see pages 141–223 in M. Kohn, A Reason for Everything: Natural Selection and the English Imagination (London: Faber and Faber, 2004).

for the beneficial chemicals in food

P. R. Mayeux, K. C. Agrawal, J. S. Tou, et al. 1988. The pharmacological effects of allicin, a constituent of garlic oil. Agents Actions 25(1–2):182–190; M. Zanolli. 2004. Phototherapy arsenal in the treatment of psoriasis. Dermatol Clin 22(4):397–406, viii; M. Heinrich and P. Bremner. 2006. Ethnobotany and ethnopharmacy—their role for anticancer drug development. Curr Drug Targets 7(3):239–245; X. Sun and D. D. Ku. 2006. Allicin in garlic protects against coronary endothelial dysfunction and right heart hypertrophy in pulmonary hypertensive rats. Am J Physiol Heart Circ Physiol (Epub May 26, 2006, ahead of print).

CHAPTER V: OF MICROBES AND MEN

the little dragon—Guinea worm (Dracunculus medinensis)

Donald G. McNeil Jr., “Dose of Tenacity Wears Down a Horrific Disease,” New York Times, March 26, 2006. For an in-depth article on the eradication program by the Carter Center see E. Ruiz-Tiben and D. R. Hopkins. 2006. Dracunculiasis (Guinea worm disease) eradication. Adv Parasitol 61:275–309. For a seminal review on the topic see R. Muller. 1971. Studies on Dracunculus medinensis (Linnaeus). II. effect of acidity on the infective larva. J Helminthol 45(2):285–288. For a real treat, such as “The parasite on attaining maturity, makes for the legs and feet,” see pages 788–795 in P. Manson and P. H. Manson-Bahr, Manson’s Tropical Diseases: A Manual of the Diseases of Warm Climates (Baltimore: W. Wood and Co. 1936). To find more information on the valiant and wide-ranging efforts of the Carter Center see www.carter center.org. For even more Guinea worm information, including how to pronounce its Latin name (dra-KUNK-you-LIE-uh-sis) properly, see the Centers for Disease Control’s website www.cdc.gov/Ncidod/dpd/parasites/ dracuncu liasis/factsht_dracunculiasis.htm. Finally, for an account of Guinea worms throughout recorded history see pages 687–689 in K. F. Kiple, The Cambridge World History of Human Disease (New York: Cambridge University Press, 1993).

sexy immunity

In the chapter “dissimilar immune systems” refers to the major histocompatibility complex (MHC), so named since they were first identified and used for transplant matching. The MHC is akin to a cellular bar code that your body uses to distinguish friend from foe. The study referred to in the chapter is C. Wedekind, T. Seebeck, F. Bettens, and A. J. Paepke. 1995. MHC-dependent mate preferences in humans. Proc Biol Sci 260(1359):245–249; for a more friendly account of this phenomenon see Martie G. Haselton, “Love Special: How to Pick a Perfect Mate,” New Scientist, April 29, 2006.

germs, germs, everywhere

F. Backhed, R. E. Ley, J. L. Sonnenburg, et al. 2005. Host-bacterial mutualism in the human intestine. Science 307(5717):1915–1920; S. R. Gill, M. Pop, R. T. Deboy, et al. 2006. Metagenomic analysis of the human distal gut microbiome. Science 312(5778):1355–1359; Rick Weiss, “Legion of Little Helpers in the Gut Keeps Us Alive,” Washington Post, June 5, 2006; C. L. Sears. 2005. A dynamic partnership: celebrating our gut flora. Anaerobe11(5):247–251; F. Guarner and J. R. Malagelada. 2003. Gut flora in health and disease. Lancet 361(9356):512–519; M. Heselmans, G. Reid, L. M. Akkermans, et al. 2005. Gut flora in health and disease: potential role of probiotics. Curr Issues Intest Microbiol 6(1):1–7; E. D. Weinberg. 1997. The Lactobacillus anomaly: total iron abstinence. Perspect Biol Med 40(4):578–583; S. Moalem, E. D. Weinberg, and M. E. Percy. 2004. Hemochromatosis and the enigma of misplaced iron: implications for infectious disease and survival. Biometals 17(2):135–139.

the orb-weaving spider (Plesiometa argyra)

W. G. Eberhard. 2000. Spider manipulation by a wasp larva. Nature 406(6793):255–256; W. G. Eberhard. 2001. Under the influence: webs and building behavior of Plesiometa argyra (Araneae, Tetragnathidae) when parasitized by Hymenoepimecis argyraphaga (Hymenoptera, Ichneumonidae). Journal of Arachnology 29:354–366; W. G. Eberhard. 2000. The natural history and behavior of Hymenoepimecis argyraphaga (Hymenoptera, Ichneumonidae) a parasitoid of Plesiometa argyra (Araneae, Tetragnathidae). Journal of Hymenoptera Research 9(2):220–240. For something less technical see Nicholas Wade, “Wasp Works Its Will on a Captive Spider,” New York Times, July 25, 2000.

“The larva somehow”

The quotes are from a BBC article, “Parasite’s Web of Death,” July 19, 2000; for the original article see news.bbc.co.uk/2/hi/science/nature/841401.htm.

the liver worm (Dicrocoelium dentriticum)

D. Otranto and D. Traversa. 2002. A review of dicrocoeliosis of ruminants including recent advances in the diagnosis and treatment. Vet Parasitol 107(4): 317–335. A website that offers a diagrammatic representation of this parasite’s complex life cycle can be found at www.parasitology.informatik.uniwuerzburg.de/login/b/me14249.png.php.

the parasitic hairworm (Spinochordodes tellinii)

Shaoni Bhattacharya, “Parasites Brainwash Grasshoppers into Death Dive,” New Scientist, August 31, 2005; the reference for the original study is D. G. Biron, L. Marche, F. Ponton, et al. 2005. Behavioural manipulation in a grasshopper harbouring hairworm: a proteomics approach. Proc Biol Sci 272(1577): 2117–2126; F. Thomas, A. Schmidt-Rhaesa, G. Martin, et al. 2002. Do hairworms (Nematomorpha) manipulate the water seeking behaviour of their terrestrial hosts? J Evol Biol 15:356–361. If you are lucky and the link is still functional, you can watch an online video of the hairworm in action as it leaves its poor drowning host at www.canal.ird.fr/canal.php?url=/prgrammes/ recherches/grillons_us/index.htm.

the rabid bite

For all there is to know about rabies see pages 597–600 in K. J. Ryan, C. G. Ray, and J. C. Sherris, Sherris Medical Microbiology: An Introduction to Infectious Diseases (New York: McGraw-Hill, 2004).

It is possible

J. Moore. 1995. The behavior of parasitized animals—when an ant is not an ant. Bioscience 45:89–96. For more on parasite manipulation see J. Moore, Parasites and the Behavior of Animals (New York: Oxford University Press, 2002). Other information was drawn from personal interviews with Professor Moore.

the feline fancier (Toxoplasma gondii)

For microscopic images of T. gondii see http://ryoko.biosci.ohio-state.edu/~parasite/toxoplasma.html. Y. Sukthana. 2006. Toxoplasmosis: beyond animals to humans. Trends Parasitol 22(3):137–142; E. F. Torrey and R. H. Yolken. 2003. Toxoplasma gondii and schizophrenia. Emerg Infect Dis 9(11):1375–1380; S. Bachmann, J. Schroder, C. Bottmer, et al. 2005. Psychopathology in first-episode schizophrenia and antibodies to Toxoplasma gondii. Psychopathology 38(2):87–90; J. P. Webster, P. H. Lamberton, C. A. Donnelly, and E. F. Torrey. 2006. Parasites as causative agents of human affective disorders? The impact of antipsychotic, mood-stabilizer and anti-parasite medication on Toxoplasma gondii’s ability to alter host behaviour. Proc Biol Sci 273(1589):1023–1030.

We found they [infected womenwere more easy-going

Quoted in Jennifer D’Angelo, “Feeling Sexy? It Could Be Your Cat,” Fox News, November 4, 2003. See also A. Skallova, M. Novotna, P. Kolbekova, et al. 2005. Decreased level of novelty seeking in blood donors infected with Toxoplasma. Neuro Endocrinol Lett 26(5):480–486; J. Flegr, M. Preiss, J. Klose, et al. 2003. Decreased level of psychobiological factor novelty seeking and lower intelligence in men latently infected with the protozoan parasite Toxoplasma gondii: dopamine, a missing link between schizophrenia and toxoplasmosis? Biol Psychol 63(3):253–268; J. Flegr, J. Havlicek, P. Kodym, et al. 2002. Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective case-control study. BMC Infect Dis 2:11; M. Novotna, J. Hanusova, J. Klose, et al. 2005. Probable neuroimmunological link between Toxoplasma and cytomegalovirus infections and personality changes in the human host. BMC Infect Dis 5:54; R. H. Yolken, S. Bachmann, I. Ruslanova, et al. 2001. Antibodies to Toxoplasma gondii in individuals with first-episode schizophrenia. Clin Infect Dis 32(5):842–844; L. Jones-Brando, E. F. Torrey, and R. Yolken. 2003. Drugs used in the treatment of schizophrenia and bipolar disorder inhibit the replication of Toxoplasma gondii. Schizophr Res 62(3):237–244. For a few articles from the popular scientific press see James Randerson, “All in the Mind?” New Scientist, October 26, 2002; David Adam, “Can a Parasite Carried by Cats Change Your Personality?” Guardian Unlimited, September 25, 2003; New Scientist Editorial Staff, “Antipsychotic Drug Lessens Sick Rats’ Suicidal Tendencies,” New Scientist, January 28, 2006; Jill Neimark, “Can the Flu Bring on Psychosis?” Discover, October 2005.

why colds make us sneeze

See pages 46 and 57 in R. M. Nesse and G. C. Williams, Why We Get Sick: The New Science of Darwinian Medicine (New York: Times Books, 1994).

fancy those pinworms

To see how many children in America are infected see the CDC website www.cdc.gov/ncidod/dpd/parasites/pinworm/factsht_pinworm.htm.

manipulative malaria

Carl Zimmer, “Manipulative Malaria Parasite Makes You More Attractive (to Mosquitoes),” New York Times, August 9, 2005.

pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS)

S. E. Swedo, H. L. Leonard, M. Garvey, et al. 1998. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 155(2):264–271; L. A. Snider and S. E. Swedo. 2004. PANDAS: current status and directions for research. Mol Psychiatry 9(10):900–907; R. C. Dale, I. Heyman, G. Giovannoni, and A. W. Church. 2005. Incidence of anti-brain antibodies in children with obsessive-compulsive disorder. Br J Psychiatry 187:314–319; S. E. Swedo and P. J. Grant. 2005. Annotation: PANDAS: a model for human autoimmune disease. J Child Psychol Psychiatry 46(3):227–234; C. Heubi and S. R. Shott. 2003. PANDAS: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections—an uncommon, but important indication for tonsillectomy. Int J Pediatr Otorhinolaryngol 67(8):837–840; Anahad O’Connor, “Can Strep Bring On an Anxiety Disorder?” New York Times, December 14, 2005; Lisa Belkin, “Can You Catch Obsessive-Compulsive Disorder?” New York Times, May 22, 2005; Nicholas Bakalar, “Tonsil-Adenoid Surgery May Help Behavior, Too,” New York Times, April 4, 2006.

It is intriguing to speculate

Quoted on page 205 in N. E. Beckage, Parasites and Pathogens: effects on Host Hormones and Behavior (New York: Chapman & Hall, 1997).

sick and lonely spiny lobsters

D. C. Behringer, M. J. Butler, and J. D. Shields. 2006. Ecology: avoidance of disease by social lobsters. Nature 441(7092):421.

why we fear strangers

J. Faulkner, M. Schaller, J. H. Park, and L. A. Duncan. 2004. Evolved disease-avoidance mechanisms and contemporary xenophobic attitudes. Group Processes & Intergroup Relations 4:333–353; L. Rózsa. 2000. Spite, xenophobia, and collaboration between hosts and parasites. Oikos 91:396–400; R. Kurzban and M. R. Leary. 2001. Evolutionary origins of stigmatization: the functions of social exclusion. Psychol Bull 127(2):187–208.

“‘Superbugs’ Spread Fear”

Anita Manning, “‘Superbugs’ Spread Fear Far and Wide,” USA Today, May 10, 2006; “Rising Deadly Infections Puzzle Experts,” Associated Press, May 12, 2006; Abigail Zuger, “Bacteria Run Wild, Defying Antibiotics,” New York Times, March 2, 2004.

staph is back

For all the facts about staph see K. J. Ryan, C. G. Ray, and J. C. Sherris, Sherris Medical Microbiology: An Introduction to Infectious Diseases (New York: McGraw-Hill, 2004). For the discovery of penicillin see page 216 in T. Rosebury, Microbes and Morals: The Strange Story of Venereal Disease (New York: Viking Press, 1971); M. C. Enright, D. A. Robinson, G. Randle, et al. 2002. The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc Natl Acad Sci 99(11):7687–7692; L. B. Rice. 2006. Antimicrobial resistance in gram-positive bacteria. Am J Med 119(6 Suppl 1):S11–S19, discussion S62–S70; K. Hiramatsu, H. Hanaki, T. Ino, et al. 1997. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother 40(1):135–136; Allison George, “March of the Super Bugs,” New Scientist, July 19, 2003.

We should be taking control

For the quotes from Ewald, and more on the evolution of the pathogenicity of cholera, see the PBS website www.pbs.org/wgbh/evolution/library/01/6/ text_pop/1_016_06.html. Roger Lewin, “Shock of the Past for Modern Medicine: A Radical Approach to Medicine Seeks to Explain Diseases and Their Symptoms as a Legacy of Our Evolution: Can Darwinism Lead to Better Treatments?” New Scientist, October 23, 1993; P. W. Ewald, Evolution of Infectious Disease (New York: Oxford University Press, 1994); P. W. Ewald. 2004. Evolution of virulence. Infect Dis Clin North Am 18(1): 1–15; Paul Ewald, “The Evolution of Virulence,” scientific American, April 1993. For an interesting interview with Professor Ewald that’s available online see www.findarticles.com/p/articles/mi_m1430/is_n6_v17/ai_16595653. Another good article is available online at www.cdc.gov/ncidod/eid/vol2no4/ ewald.htm.

CHAPTER VI: JUMP INTO THE GENE POOL

Edward Jenner and smallpox

A. J. Stewart and P. M. Devlin. 2006. The history of the smallpox vaccine. J Infect 52(5):329–334; for more on the history of smallpox see K. F. Kiple, The Cambridge World History of Human Disease (New York: Cambridge University Press, 1993).

how many genes do we have?

L. D. Stein. 2004. Human genome: end of the beginning. Nature 431(7011): 915–916.

junk DNA

“The word: Junk DNA,” New Scientist, November 19, 2005; Wayt Gibbs, “The Unseen Genome: Gems among the Junk,” scientific American, November 2003. This article is a little dated but still good: Natalie Angier, “Keys Emerge to Mystery of ‘Junk’ DNA,” New York Times, June 28, 1994. Junk DNA finally gets an upgrade, in P. Andolfatto. 2005. Adaptive evolution of non-coding DNA in Drosophila. Nature 437(7062):1149–1152; James Kingsland, “Wonderful Spam,” New Scientist, May 29, 2004.

mitochondria

For more on the fascinating story behind mitochondria, those lovable little organelles, see Philip Cohen, “The Force,” New Scientist, February 26, 2000.

solar radiation

D. S. Smith, J. Scalo, and J. C. Wheeler. 2004. Importance of biologically active aurora-like ultraviolet emission: stochastic irradiation of Earth and Mars by flares and explosions. Orig Life Evol Biosph 34(5):513–532; K. G. Mc-Cracken, J. Beer, and F. B. McDonald. 2004. Variations in the cosmic radiation, 1890–1986, and the solar and terrestrial implications. Ad Space Res 34:397–406; T. I. Pulkkinen, H. Nevanlinna, P. J. Pulkkinen, and M. Lockwood. 2001. The Sun-Earth connection in time scales from years to decades and centuries. Space Science Reviews 95(1/2):625–637; H. S. Hudson, S. Silva, and M. Woodard. 1982. The effects of sunspots on solar radiation. Solar Physics76:211–219; Malcolm W. Browne, “Flu Time: When the Sunspots Are Jumping?” New York Times, January 25, 1990; F. Hoyle and N. C. Wickramasinghe. 1990. Sunspots and influenza. Nature 343(6256):304; J. W. Yeung. 2006. A hypothesis: sunspot cycles may detect pandemic influenza A in 1700–2000 a.d. Med Hypotheses 67(5):1016–1022.

shuffling genes

One example of the incredible power of genes to rearrange themselves is seen in the fruit fly gene called Dscam. Genes are rearranged through an enzymatic “card shuffler” called a spliceosome. The Dscam gene is truly amazing, since it can produce 38,016 different and distinct proteins. For a sample of papers on Dscam see J. M. Kreahling and B. R. Graveley. 2005. The iStem, a long-range RNA secondary structure element required for efficient exon inclusion in the Drosophila Dscam pre-mRNA. Mol Cell Biol 25(23):10251–10260; A. M. Celotto and B. R. Graveley. 2001. Alternative splicing of the Drosophila Dscam pre-mRNA is both temporally and spatially regulated. Genetics 159(2):599–608; G. Parra, A. Reymond, N. Dabbouseh, et al. 2006. Tandem chimerism as a means to increase protein complexity in the human genome. Genome Res 16(1):37–44.

biological Kaizen

A book on the ethos of continual improvement from a business perspective: M. Ima, Kaizen (Ky’zen), the Key to Japan’s Competitive Success (New York: Random House Business Division, 1986).

the surprise “KO”: animals with missing genes are normal

See pages 64–82 in M. Morange, The Misunderstood Gene (Cambridge, MA: Harvard University Press, 2001).

life at the end of the genome

See pages 183–198 in I. Moss, What Genes Can’t Do (Cambridge, MA: MIT Press, 2003); H. Pearson. 2006. Genetics: what is a gene? Nature 441(7092): 398–401.

Jean-Baptiste Lamarck

A very strange period in the study of heritability by Soviet scientists was shaped largely by Trofim Denisovich Lysenko. Lysenkoism, as it came to be

known, was an extreme twist on acquired characteristics. For more on this fascinating period in history see pages 183–187 in M. Kohn, A Reason for Everything: Natural Selection and the English Imagination (London: Faber and Faber, 2004); C. Darwin, The Origin of the Species (New York: Fine Creative Media, 2003).

attention undoubtedly will be centered

“The Significance of Responses of the Genome Challenge,” December 8, 1983, available at www.nobelprize.org/nobel_prizes/medicine/laureates/ 1983/mcclintock-lecture.pdf. For a great online resource from the U.S. National Library of Medicine about McClintock see www.profiles.nlm.nih.gov/ LL/Views/Exhibit/narrative/biographical.html. Also see Vidyanand Nanjundiah, “Barbara McClintock and the Discovery of Jumping Genes,” Resonance,October 1996.

a fly named “Methuselah”

Y. J. Lin, L. Seroude, and S. Benzer. 1998. Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 282(5390):943–946; for a fun article on how you might be the next Methuselah see Kate Douglas, “How to Live to 100…and Enjoy It,” New Scientist, June 3, 2006.

stars of the transposable world: gypsy, mtanga, Castaway, Evelknievel, mariner

J. Modolell, W. Bender, and M. Meselson. 1983. Drosophila melanogaster mutations suppressible by the suppressor of Hairy-wing are insertions of a 7.3-kilobase mobile element. Proc Natl Acad Sci U S A 80(6):1678–1682; C. J. Rohr, H. Ranson, X. Wang, and N. J. Besansky. 2002. Structure and evolution of mtanga, a retrotransposon actively expressed on the Y chromosome of the African malaria vector Anopheles gambiae. Mol Biol Evol 19(2):149–162; T. E. Bureau, P. C. Ronald, and S. R. Wessler. 1996. A computer-based systematic survey reveals the predominance of small inverted-repeat elements in wild-type rice genes. Proc Natl Acad Sci U S A 93(16):8524–8529; S. Henikoff and L. Comai. 1998. A DNA methyltransferase homolog with a chromo-domain exists in multiple polymorphic forms in Arabidopsis. Genetics 149(1): 307–318; J. W. Jacobson, M. M. Medhora, and D. L. Hartl. 1986. Molecular structure of a somatically unstable transposable element in Drosophila. Proc Natl Acad Sci U S A 83(22):8684–8688; S. M. Miller, R. Schmitt, and D. L. Kirk. 1993. Jordan, an active Volvox transposable element similar to higher plant transposons. Plant Cell 5(9):1125–1138.

The genome has long been thought

G. G. Dimijian. 2000. Pathogens and parasites: strategies and challenges. Proc (Bayl Univ Med Cent) 13(1):19–29.

making a mutant

The papers mentioned in the study are J. Cairns, J. Overbaugh, and S. Miller. 1988. The origin of mutants. Nature 335(6186):142–145; B. G. Hall. 1990. Spontaneous point mutations that occur more often when advantageous than when neutral. Genetics 126(1):5–16; S. M. Rosenberg. 1997. Mutation for survival. Curr Opin Genet Dev 7(6):829–834; J. Torkelson, R. S. Harris, M. J. Lombardo, et al. 1997. Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation. Embo J 16(11):3303–3311; P. L. Foster. 1997. Nonadaptive mutations occur on the F’ episome during adaptive mutation conditions in Escherichia coli. J Bacteriol 179(5):1550–1554; O. Tenaillon, E. Denamur, and I. Matic. 2004. Evolutionary significance of stress-induced mutagenesis in bacteria. Trends Microbiol 12(6):264–270. For Matic’s study that was mentioned in the chapter see I. Bjedov, O. Tenaillon, B. Gerard, et al. 2003. Stress-induced mutagenesis in bacteria. Science 300(5624):1404–1409.

genes that increase the risk of cancer: BRCA1 and BRCA2

For a good resource that covers many common conditions and their associated genetics see P. Reilly, Is It in Your Genes? The influence of Genes on Common Disorders and Diseases That affect You and Your Family (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 2004).

“You wouldn’t want that added element”

Professor Fred Gage, quoted in a press release available at genome.wellcome.ac.uk/doc_WTD020792.html. For the jumping genes within the brain article see A. R. Muotri, V. T. Chu, M. C. Marchetto, et al. 2005. Somatic mosaicism in neuronal precursor cells mediated by LI retrotransposition. Nature 435(7044):903–910.

Hermes behaves more like

Nancy Craig, quoted in a press release available at www.hopkinsmedicine.org/Press_releases/2004/12_23_04.html. The study Nancy Craig is talking of is L. Zhou, R. Mitra, P. W. Atkinson, et al. 2004. Transposition of hAT elements links transposable elements and V(D)J recombination. Nature 432(7020):995–1001. Also see M. Bogue and D. B. Roth. 1996. Mechanism of V(D)J recombination. Curr Opin Immunol 8(2):175–180.

our genes show signs of jumping genes

For more on this fascinating idea see James Kingsland, “Wonderful Spam,” New Scientist, May 29, 2004.

have been remodeling

Jef Boeke, quoted at www.eurekalert.org/pub_releases/2002-08/jhmi gc081502.php. The original paper that Professor Boeke is commenting on is D. E. Symer, C. Connelly, S. T. Szak, et al. 2002. Human 11 retrotransposition is associated with genetic instability in vivo. Cell 110(3):327–338.

half the genome from jumping genes

P. Medstrand, L. N. van de Lagemaat, C. A. Dunn, et al. 2005. Impact of transposable elements on the evolution of mammalian gene regulation. Cytogenet Genome Res 110(1–4):342–352; W. Makalowski. 2001. The human genome structure and organization. Acta Biochim Pol 48(3):587–598.

at least 8 percent of the human genome is composed of retroviruses

J. F. Hughes and J. M. Coffin. 2004. Human endogenous retrovirus K solo-LTR formation and insertional polymorphisms: implications for human and viral evolution. Proc Natl Acad Sci U S A 101(6):1668–1672; S. Mi, X. Lee, X. Li, et al. 2000. Syncytin is a captive retroviral envelope protein involved

in human placental morphogenesis. Nature 403(6771):785–789; J. P. Moles, A. Tesniere, and J. J. Guilhou. 2005. A new endogenous retroviral sequence is expressed in skin of patients with psoriasis. Br J Dermatol 153(1):83–89.

“the successful genetic patterns”

See pages 1–10 in Salvador E. Luria, Virus Growth and Variation, B. Lacey and I. Isaacs, eds. (Cambridge: Cambridge University Press, 1959).

There’s a very strong

Luis Villarreal, personal communication. For more of his work see L. P. Villarreal. 2004. Can viruses make us human? Proc Am Phil So 148(3):296–323. L. P. Villarreal, Viruses and the Evolution of Life (Washington, DC: ASM Press, 2005); L. P. Villareal. 1997. On viruses, sex, and motherhood. J Virol 71(2):859–865.

more on viruses as a precursor to life and evolution

Charles Siebert, “Unintelligent Design,” Discover, March 2006; M. Syvanen. 1984. The evolutionary implications of mobile genetic elements. Annu Rev Genet 18:271–293; D. J. Hedges and M. A. Batzer. 2005. From the margins of the genome: mobile elements shape primate evolution. Bioessays 27(8):785–794; M. G. Kidwell and D. R. Lisch. 2001. Perspective: transposable elements, parasitic DNA, and genome evolution. Evolution Int J Org Evolution55(1): 1–24; J. Brosius. 2005. Echoes from the past—are we still in an RNP world? Cytogenet Genome Res 110(1–4):8–24; C. Biemont and C. Vieira. 2005. What transposable elements tell us about genome organization and evolution: the case of Drosophila. Cytogenet Genome Res 110(1–4):25–34; P. Medstrand, L. N. van de Lagemaat, C. A. Dunn, et al. 2005. Impact of transposable ele

ments on the evolution of mammalian gene regulation. Cytogenet Genome Res 110(1–4):342–352.

CHAPTER VII: METHYL MADNESS: ROAD TO THE FINAL PHENOTYPE

American children are overweight or obese

For a book on the topic see F. M. Berg, Underage & Overweight: The Childhood Obesity Crisis: What Every Family Needs to Know (Long Island City, NY: Hatherleigh Press, 2005). On the marketing of fast food to children, for younger readers and adults alike, see E. Schlosser and C. Wilson, Chew on This: The

Unhappy Truth about Fast Food (Boston: Houghton Mifflin Company, 2006). For a short online article from the University of California including useful references see news.ucanr.org/mediakits/Nutrition/nutritionfactsheet.shtml. For an in-depth account of “Behavioral Risk Factor Surveillance” from the CDC see www.cdc.gov/mmwr/preview/mmwrhtml/ss4906a1.htm. Also see W. H. Dietz and T. N. Robinson. 2005. Clinical practice: overweight children and adolescents. N Engl J Med 352(20):2100–2109; D. S. Freedman, W. H. Dietz, S. R. Srinivasan, and G. S. Berenson. 1999. The relation of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa Heart Study. Pediatrics 103(6 Pt 1):1175–1182. S. J. Olshansky, D. J. Passaro, R. C. Hershow, et al. 2005. A potential decline in life expectancy in the United States in the 21st century. N Engl J Med 352(11):1138–1145; Philip Cohen, “You Are What Your Mother Ate, Suggests Study,” New Scientist, August 4, 2003. The study that the New Scientist article is referring to is R. A. Waterland and R. L. Jirtle. 2003. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23(15):5293–5300; Alison Motluk, “Life Sentence,” New Scientist, October 30, 2004.

flicking the switch: environmental factors

Rowan Hooper, “Mendel’s Laws of Inheritance Challenged,” New Scientist, May 27, 2006; Rowan Hooper, “Men Inherit Hidden Cost of Dad’s Vices,” New Scientist, January 6, 2006; E. Jablonka and M. J. Lamb, Evolution in Four Dimensions: Genetic, Epigenetic, Behavioral, and Symbolic Variation in the History of Life (Cambridge, MA: MIT Press, 2005); R. A. Waterland and R. L. Jirtle. 2003. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23(15):5293–5300; Gaia Vince, “Pregnant Smokers Increase Grandkids’ Asthma Risk,” New Scientist, April 11, 2005; Q. Li, S. Guo-Ross, D. V. Lewis, et al. 2004. Dietary prenatal choline supplementation alters postnatal hippocampal structure and function. J Neurophysiol 91(4):1545–1555; Shaoni Bhattacharya, “Nutrient During Pregnancy Super-Charges’ Brain,” New Scientist, March 12, 2004; Leslie A. Pray, “Dieting for the Genome Generation,” The Scientist, January 17, 2005; Anne Underwood and Jerry Adler, “Diet and Genes,” Newsweek, January 24, 2005.

We have long known

Randy Jirtle, quoted in a press release, Duke University Medical Center, available at www.dukemednews.org/news/article.php?id=6804. For the full article see R. A. Waterland and R. L. Jirtle. 2003. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23(15):5293–5300; Leslie A. Pray, “Epigenetics: Genome, Meet Your Environment: As the Evidence Accumulates for Epigenetics, Researchers Reacquire a Taste for Lamarkism,” The Scientist, July 5, 2004; I. C. Weaver, N. Cervoni, F. A. Champagne, et al. 2004. Epigenetic programming by maternal behavior. Nat Neurosci 7(8):847–854; E. W. Fish, D. Shahrokh, R. Bagot, et al. 2004. Epigenetic programming of stress responses through variations in maternal care. Ann N Y Acad Sci 1036:167–180; A. D. Riggs and Z. Xiong. 2004. Methylation and epigenetic fidelity. Proc Natl Acad Sci U S A 101(1): 4–5.

baby voles

C. R. Camargo, E. Colares, and A. M. Castrucci. 2006. Seasonal pelage color change: news based on a South American rodent. An Acad Bras Cienc 78(1):77–86.

Daphnia gives birth to babies with helmets

J. L. Brooks. 1965. Predation and relative helmet size in cyclomorphic Daphnia. Proc Natl Acad Sci U S A 53(1):119–126; J. Pijanowska and M. Kloc. 2004. Daphnia response to predation threat involves heat-shock proteins and the actin and tubulin cytoskeleton. Genesis 38(2):81–86.

insects change their colors

M. Enserink. 2004. Entomology: an insect’s extreme makeover. Science 306(5703):1881.

what mama lizard smelled

R. Richard Shine and S. J. Downes. 1999. Can pregnant lizards adjust their off spring phenotypes to environmental conditions? Oecologia 119(1):1–8.

maternal effect

P. D. Gluckman and M. Hanson, The Fetal Matrix: Evolution, Development, and Disease (New York: Cambridge University Press, 2005).

Barker Hypothesis

Shaoni Bhattacharya, “Fattening Up Skinny Toddlers Risks Heart Health,” New Scientist, October 27, 2005; C. N. Hales and D. J. Barker. 2001. The thrifty phenotype hypothesis. Br Med Bull 60:5–20.

the first four days of pregnancy

W. Y. Kwong, A. E. Wild, P. Roberts, et al. 2000. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development127(19):4195–4202. For a good review of the topic see V. M. Vehaskari and L. L. Woods. 2005. Prenatal programming of hypertension: lessons from ex

perimental models. J Am Soc Nephrol 16(9):2545–2556.

men who smoke before puberty

Rowan Hooper, “Men Inherit Hidden Cost of Dad’s Vices,” New Scientist, January 6, 2006; M. E. Pembrey, L. O. Bygren, G. Kaati, et al. 2006. Sexspecific, male-line transgenerational responses in humans. Eur J Hum Genet14(2):159–166. The quote from Marcus Pembrey is from E. Pennisi. 2005. Food, tobacco, and future generations. Science 310(5755):1760–1761.

grandmothers who smoked while pregnant

Gaia Vince, “Pregnant Smokers Increase Grandkids’ Asthma Risk,” New Scientist, April 11, 2005.

“Hunger Winter”

L. H. Lumey, A. C. Ravelli, L. G. Wiessing, et al. 1993. The Dutch Famine Birth Cohort Study: design, validation of exposure, and selected characteristics of subjects after 43 years follow-up. Paediatr Perinat Epidemiol 7(4):354–367; A. D. Stein, A. C. Ravelli, and L. H. Lumey. 1995. Famine, third-trimester pregnancy weight gain, and intrauterine growth: the Dutch Famine Birth

Cohort Study. Hum Biol 67(1):135–150; L. H. Lumey, A. D. Stein, and A. C. Ravelli. 1995. Timing of prenatal starvation in women and birth weight in their first and second born off spring: the Dutch Famine Birth Cohort Study. Eur J Obstet Gynecol Reprod Biol 61(1):23–30; L. H. Lumey and A. D. Stein. 1997. In utero exposure to famine and subsequent fertility: the Dutch Famine Birth Cohort Study. Am J Public Health 87(12):1962–1966; A. D. Stein and L. H. Lumey. 2000. The relationship between maternal and off spring birth weights after maternal prenatal famine exposure: the Dutch Famine Birth Cohort Study. Hum Biol 72(4):641–654.

Our findings show

R. A. Waterland and R. L. Jirtle. 2003. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23(15):5293–5300.

We believe these different epigenetic patterns

Christen Brownlee, “Nurture Takes the Spotlight,” Science News, June 24, 2006.

Epigenomics

The company website can be found at www.epigenomics.de/en/Company/. For more on the subject of epigenetics see G. Riddihough and E. Pennisi. 2001. The evolution of epigenetics. Science 293(5532):1063; E. Jablonka and M. J. Lamb. 2002. The changing concept of epigenetics. Ann N Y Acad Sci 981:82–96; V. K. Rakyan, J. Preis, H. D. Morgan, and E. Whitelaw. 2001. The marks, mechanisms and memory of epigenetic states in mammals. Biochem J356(Pt 1):1–10.

smoking and methylation

D. H. Kim, H. H. Nelson, J. K. Wiencke, et al. 2001. p16(INK4a) and histology-specific methylation of CpG islands by exposure to tobacco smoke in non–small cell lung cancer. Cancer Res 61(8):3419–3424; H. Enokida, H. Shiina, S. Urakami, et al. 2006. Smoking influences aberrant CpG hypermethylation of multiple genes in human prostate carcinoma. Cancer 106(1): 79–86.

“We’d like to use the degree”

Dr. Dhananjaya Saranath, quoted at www.telegraphindia.com/1050214/asp/ knowhow/story_4376851.asp.

folic acid and neural tube defects

There is a very large literature on this subject; for a sample paper (albeit a bit dated but still good) see MRC Vitamin Study Research Group. 1991. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 338(8760):131–137, and more to the point: C. M. Ulrich and J. D. Potter. 2006. Folate supplementation: too much of a good thing? Cancer Epidemiol Biomarkers Prev 15(2):189–193.

betamethasone and hyperactivity

For the University of Toronto study mentioned in the chapter see A. Kapoor, E. Dunn, A. Kostaki, et al. 2006. Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids. J Physiol 572(Pt 1):31–44; P. Erdeljan, M. H. Andrews, J. F. MacDonald, and S. G. Matthews. 2005. Glucocorticoids and serotonin alter glucocorticoid receptor mRNA levels in fetal guinea-pig hippocampal neurons, in vitro. Reprod Fertil Dev17(7):743–749. The quote in the chapter, “terrifying beyond comprehension,” is from Alison Motluk, “Pregnancy Drug Can affect Grandkids Too,” New Scientist, December 3, 2005.

This is the first approved drug

Peter Jones, quoted in Lori Oliwenstein, “USC Cancer Researchers Examine Potential of Epigenetics in Nature,” HSC Weekly, May 28, 2004.

It is apparent

G. Egger, G. Liang, A. Aparicio, and P. A. Jones. 2004. Epigenetics in human disease and prospects for epigenetic therapy. Nature 429(6990):457–463.

Johns Hopkins and azacitidine

D. Gius, H. Cui, C. M. Bradbury, et al. 2004. Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed

by a multimodality approach. Cancer Cell 6(4):361–371; R. S. Tuma. 2004. Silencing the critics: studies move closer to answering epigenetic questions. J Natl Cancer Inst 96(22):1652–1653; M. Z. Fang, Y. Wang, N. Ai, et al. 2003. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 63(22):7563–7570.

What is good in small amounts

Dana Dolinoy, quoted in a press release available at www.dukemednews.org/ news/article.php?id=9584. D. C. Dolinoy, J. R. Weidman, R. A. Waterland, and R. L. Jirtle. 2006. Maternal genistein alters coat color and protects Avy mouse off spring from obesity by modifying the fetal epigenome. Environ Health Perspect 114(4):567–572. Also see M. Z. Fang, D. Chen, Y. Sun, et al. 2005. Reversal of hypermethylation and reactivation of p16INK4a, RARbeta,and MGMT genes by genistein and other isoflavones from soy. Clin Cancer Res 11(19 Pt 1):7033–7041.

pregnancy and stress

For the study about 9/11 see R. Catalano, T. Bruckner, J. Gould, et al. 2005. Sex ratios in California following the terrorist attacks of September 11, 2001. Hum Reprod 20(5):1221–1227; for the study mentioned about the stress faced by East German mothers during reunification see R. A. Catalano. 2003. Sex ratios in the two Germanies: a test of the economic stress hypothesis. Hum Reprod 18(9):1972–1975; for the study after the war in Slovenia see B. Zorn, V. Sucur, J. Stare, and H. Meden-Vrtovec. 2002. Decline in sex ratio at birth after 10-day war in Slovenia: brief communication. Hum Reprod 17(12):3173–3177; for the effects of the Kobe earthquake on birth ratios see M. Fukuda, K. Fukuda, T. Shimizu, and H. Moller. 1998. Decline in sex ratio at birth after Kobe earthquake. Hum Reprod 13(8):2321–2322; Hazel Muir, “Women Who Believe in Long Life Bear Sons,” New Scientist, August 4, 2004; for the original study see S. E. Johns. 2004. Subjective life expectancy predicts off spring sex in a contemporary British population. Proc Biol Sci 271(Suppl 6):S474–S476; Will Knight, “9/11 Babies Inherit Stress from Mothers,” New Scientist, May 3, 2005.

“all the pages of a manual”

National Human Genome Research Institute, www.genome.gov/11006943.

the Human Epigenome Project

Shaoni Bhattacharya, “Human Gene On/Off Switches to Be Mapped,” New Scientist, October 7, 2003; P. A. Jones and R. Martienssen. 2005. A blueprint for a Human Epigenome Project: the AACR Human Epigenome Workshop. Cancer Res 65(24):11241–11246. A brief online article can be found from the American Association for Cancer Research at www.aacr.org/Default.aspx?p=6336&d=562.

CHAPTER VIII: THAT’S LIFE: WHY YOU AND YOUR iPOD MUST DIE

Seth Cook

Carol Smith, “Lessons from a Boy Growing Old before His Time,” Seattle Post-Intelligencer Reporter, September 16, 2004; there’s also an ABC News story about Seth at abcnews.go.com/GMA/Health/story?id=1445002. For more information on this condition visit the Hutchinson-Gilford Progeria Syndrome Network website at www.hgps.net; also the Progeria Research Foundation has an excellent website with a lot of information at www.progeriaresearch.org/progeria_101.html.

researchers announce finding mutation that causes progeria

M. Eriksson, W. T Brown, L. B. Gordon, et al. 2003. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423(6937):293–298.

reported in Science

P. Scaffidi and T. Misteli. 2006. Lamin A–dependent nuclear defects in human aging. Science 312(5776):1059–1063.

Leonard Hayflick and his number

L. Hayflick. 1965. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–616; D. Josefson. 1998. US scientists extend the life of

human cells. BMJ 316:247–252; L. Hayflick. 2000. The illusion of cell immortality. Br J Cancer 83(7):841–846.

cancer versus other conditions

See Cancer Facts and Figures—2006 from the American Cancer Society’s website at www.cancer.org/downloads/STT/CAFF2006PWSecured.pdf. Also see T. Thom, N. Haase, W. Rosamond, et al. 2006. Heart disease and stroke statistics—2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 113(6):e85–151.

most cancer cells use telomerase

See an online article from the Whitehead Institute’s website at www.wi.mit.edu/news/archives/1997/rw_0814.html.

stem cells

There is a bounty of articles on this topic; for one that is a little dated but well written see Nicholas Wade, “Experts See Immortality in Endlessly Dividing Cells,” New York Times, November 17, 1998.

long life and DNA repair

G. A. Cortopassi and E. Wang. 1996. There is substantial agreement among interspecies estimates of DNA repair activity. Mech Ageing Dev 91(3): 211–218.

biogenic obsolescence

For a fascinating account of “planned obsolescence” see G. Slade, Made to Break: Technology and Obsolescence in America (Cambridge, MA: Harvard University Press, 2006). For an interesting look at Apple’s use of planned obsolescence in its design of the ever-popular iPod see www.cerge.cuni.cz/ pdf/events/papers/060410_t.pdf.

a molecular Band-Aid for progeria?

“Breakthrough in Premature Ageing,” New Scientist, March 12, 2005; P. Scaff di and T. Misteli. 2005. Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med 11(4):440–445.

big baby small pelvis

For more on childbirth from an evolutionary perspective see pages 183–203 in W. Trevathan, E. O. Smith, and J. J. McKenna, Evolutionary Medicine (New York: Oxford University Press, 1999); K. R. Rosenberg and W. R. Trevathan, “The Evolution of Human Birth,” scientific American, November 2001; H. Nelson, R. Jurmain, and L. Kilgore, Essentials of Physical Anthropology (St. Paul, MN: West Publishing, 1992).

“Our ancestors entered the Pliocene”

Elaine Morgan, personal communication. The Descent of Woman (New York: Stein and Day, 1972); E. Morgan, The Aquatic Ape Hypothesis (London: Souvenir Press, 1997); E. Morgan, The Aquatic Ape: A Theory of Human Evolution (London: Souvenir Press, 1982); E. Morgan, The Scars of Evolution (New York: Oxford University Press, 1994); E. Morgan, The Descent of the Child: Human Evolution from a New Perspective (New York: Oxford University Press, 1995); A. C. Hardy, “Was Man More Aquatic in the Past?” New Scientist, March 17, 1960; F. W. Jones, Man’s Place among the Mammals (New York, London: Longmans, E. Arnold & Co., 1929); Kate Douglas, “Taking the Plunge,” New Scientist, November 25, 2000. For an interview with Elaine Morgan see Kate Douglas, “Interview: The Natural Optimist,” New Scientist, April 23, 2005.

never really “got” what the theory was

A. Kuliukas. 2002. Wading for food the driving force of the evolution of bipedalism? Nutr Health 16(4):267–289. See also Libby Brooks, “Come on in—the Water’s Lovely,” Guardian, May 1, 2003.

water babies

The study mentioned in the chapter is R. E. Gilbert and P. A. Tookey. 1999. Perinatal mortality and morbidity among babies delivered in water: surveillance study and postal survey. BMJ 319(7208):483–487. For a beautiful illustrated book with many photographs of mothers giving birth and swimming with their children see J. Johnson and M. Odent, We Are All Water Babies (Berkeley, CA: Celestial Arts Publishing, 1995); E. R. Cluett, R. M. Pickering, K. Getliffe, and N. J. St George Saunders. 2004. Randomised controlled trial of labouring in water compared with standard of augmentation for management of dystocia in first stage of labour. BMJ 328(7435):314; E. R. Cluett, V. C. Nikodem, R. E. McCandlish, and E. E. Burns. 2004. Immersion in wa

ter in pregnancy, labour and birth. Cochrane Database Syst Rev (2):CD000111. For the Italian study mentioned in the text see A. Thoeni, N. Zech, L. Moroder, and F. Ploner. 2005. Review of 1600 water births: does water birth increase the risk of neonatal infection? J Matern Fetal Neonatal Med 17(5):357–361. Water birthing is not without controversy; to see a study that found no positive correlation see K. Eckert, D. Turnbull, and A. MacLennan. 2001. Immersion in water in the first stage of labor: a randomized controlled trial. Birth 28(2):84–93.

episiotomy

As all medical procedures do, episiotomies show a marked variation in how often they are performed in different countries. For example, rates of episiotomies in the United States are still above 30 percent as compared to about 10 percent of births in northern Europe. For more details see S. B. Th acker and H. D. Banta. 1983. benefits and risks of episiotomy: an interpretative review of the English language literature, 1860–1980. Obstet Gynecol Surv38(6):322–338; for possible alternatives to episiotomies see M. M. Beckmann and A. J. Garrett. 2006. Antenatal perineal massage for reducing perineal trauma. Birth 33(2):159.

Dr. Myrtle McGraw and “water-friendly” behavior

M. B. McGraw, The Neuromuscular Maturation of the Human Infant (New York: Columbia University Press, 1943).