PERSPECTIVE Hepatitis C and the Criminal Justice System From the Departments of Medicine and and control of hepatitis B and C. Washing- 4. Varan AK, Mercer DW, Stein MS, Spaulding Epidemiology, Brown University (J.D.R.), and ton, DC: National Academies Press, 2010. AC. Hepatitis C seroprevalence among pris- the Center for Prisoner Health and Human 2. Rein DB, Wittenborn JS, Weinbaum CM, on inmates since 2001: still high but declin- Rights, Miriam Hospital (J.D.R., S.A.A.) — Sabin M, Smith BD, Lesesne SB. Forecasting ing. Public Health Rep 2014;129:187-95. both in Providence, RI; the University of the morbidity and mortality associated with 5. Rich JD, Chandler R, Williams BA, et al. California Riverside School of Medicine, prevalent cases of pre-cirrhotic chronic hep- How health care reform can transform the Riverside (S.A.A.); and the Division of Geri- atitis C in the United States. Dig Liver Dis health of criminal justice-involved individu- atrics, Department of Medicine, University 2011;43:66-72. als. Health Aff (Millwood) 2014;33:462-7. of California, San Francisco (B.A.W.). 3. Rich JD, Wakeman SE, Dickman SL. Medicine and the epidemic of incarceration DOI: 10.1056/NEJMp1311941 1. Institute of Medicine. Hepatitis and liver in the United States. N Engl J Med 2011;364: Copyright © 2014 Massachusetts Medical Society. cancer: a national strategy for prevention 2081-3. HISTORY OF MEDICINE The Biology and Genetics of Obesity — A Century of Inquiries Chin Jou, Ph.D. Related article, p. 1909 he obese lack willpower; they Noorden delineated two types of case that some people were pre- Tovereat and underexercise — obesity: exogenous and endoge- disposed to obesity. or so believe a majority of Amer- nous (1953; see box for historical In the 1950s, for instance, the icans. A 2012 online poll of 1143 Journal articles cited). Exogenous work of Rockefeller University’s adults conducted by Reuters and obesity, which accounted for most Jules Hirsch showed that for the market research firm Ipsos cases, was the consequence of obese people, long-term weight found that 61% of U.S. adults external culprits — namely, food loss is a lifelong struggle. Hirsch believed that “personal choices consumption in excess of energy found that although obese sub- about eating and exercise” were expenditure. But some people jects could shed a substantial responsible for the obesity epi- had endogenous obesity, caused amount of weight through dras- demic.1 A majority of Ameri- by hypometabolism or other thy- tic calorie restriction, their meta- cans, it seems, remain unaware roid disorders. bolic rates would dip in response of or unconvinced by scientific Some early-20th-century doc- to calorie reductions. This effect research suggesting that “per- tors bluntly dismissed the idea of meant, for example, that if an sonal choices” may not account endogenous obesity. George Van obese woman dropped down for all cases of obesity. Ness Dearborn, a neuropsychia- from 200 lb to 130 lb, she would Yet for more than a century, trist who had been on the faculty have to consume fewer calories to physicians have been proposing at Harvard and Tufts, declared in remain at 130 lb than would a that some cases of obesity are a 1917 that “the great and culpable 130-lb counterpart whose weight function of innate biologic mech- majority of the obese achieve had always held steady. The pre- anisms or heredity. In 1907, the their uncomplimentary fatness.”2 viously obese woman, then, re- German pathologist Carl von Nonetheless, a survey of medical quired more “willpower” to main- journal articles on obesity in the tain her reduced weight than Historical New England Journal of Medicine 1910s and 1920s reveals that someone who had never been Articles Cited. even physicians who might have obese. Decades later, in 1995, shared Dearborn’s sentiments Hirsch and his former Rockefeller 1953. Pennington AW. A reorientation on obesity. 248:959-64. conceded that dietary excess and colleagues Rudolph Leibel and 1986. Stunkard AJ, Sørensen TIA, Hanis C, et al. lack of exercise could not ac- Michael Rosenbaum observed that An adoption study of human obesity. count for all cases of overweight. just as the metabolism of sub- 314:193-8. 1990a. Bouchard C, Tremblay A, Després JP, et al. And although the hypometabolic jects who had lost 10% of their The response to long-term overfeeding in thesis had fallen out of favor by body weight decelerated, the identical twins. 322:1477-82. 1930, when more accurate calcu- metabolism of those who had 1990b. Stunkard AJ, Harris JR, Pedersen NL, McClearn GE. The body-mass index of twins lations of body-surface area indi- gained 10% of their body weight who have been reared apart. 322:1483-7. cated that the metabolic rates of revved up (1995). These findings 1995. Leibel RL, Rosenbaum M, Hirsch J. the obese were normal, research- suggested that the body has built- Changes in energy expenditure resulting from altered body weight. 332:621-8. ers in the second half of the 20th in mechanisms that resist attempts century continued to make the to resize it for the long term. 1874 n engl j med 370;20 nejm.org may 15, 2014 The New England Journal of Medicine Downloaded from nejm.org on December 13, 2017. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved. PERSPECTIVE The Biology and Genetics of Obesity B Historical Ads for Weight-Loss Products. The ad for obesity soap is from 1903; the ad for Graybar is from the 1920s; and the ad for Appetrol, which appeared in the Journal, is from 1960. Courtesy of the Advertising Archives. A slide show containing additional ads is available with the full text of this article at NEJM.org. n engl j med 370;20 nejm.org may 15, 2014 1875 ICM AUTHOR Jou RETAKE 1st REG F FIGUREThe New 1 England Journal of Medicine2nd CASE 3rd Downloaded from nejm.org onTITLE December 13, 2017. For personal useRevised only. No other uses without permission. CopyrightEMail © 2014 MassachusettsLine Medical4-C Society. All rights reserved. SIZE Enon ARTIST: mst H/T H/T FILL Combo 39p6 AUTHOR, PLEASE NOTE: Figure has been redrawn and type has been reset. Please check carefully. JOB: 37019 ISSUE: 5-15-14 PERSPECTIVE The Biology and Genetics of Obesity In the 1960s, prisoner feeding of their study. They found that, was little difference in weight experiments by University of Ver- despite having shared an environ- gain and even less difference in mont physician–researcher Ethan ment with their adoptive parents, body-fat distribution and visceral- Sims also pointed toward meta- the adoptees’ body-mass indexes fat accumulation. bolic homeostasis. In 1967, Sims approximated those of their bio- While twin studies and feed- fed inmates at the Vermont State logic parents rather than their ing experiments continued, obe- Prison upwards of 10,000 kcal per adoptive parents. Accordingly, sity research also took a decid- day. Over 200 days on this over- most adoptees inherited their bio- edly molecular turn with the feeding regimen, 20 inmates logic parents’ obesity: four fifths discovery of the peptide hormone gained an average of 20 to 25 lb.3 of those with two obese biologic and satiety factor leptin in 1994. The metabolic rates of these pre- parents were obese, as compared Building on the work that Doug- viously normal-weight subjects with one seventh of those with las Coleman had been conduct- sped up in response to their in- normal-weight biologic parents. ing at the Jackson Laboratory creased caloric consumption, as Four years later, Stunkard and since the 1960s, as well as the if to defend their initial, lower another team of researchers used mapping of obesity-gene muta- weights. The men had difficulty another twin registry, this time tions in mice performed by Leibel maintaining weight gain, and from Sweden, to find more sup- et al. in the 1980s and early most shed all the weight they port for the genetics of weight 1990s, Jeffrey Friedman and col- had gained relatively easily once regulation (1990b). The Swedish leagues at Rockefeller University their calorie intake returned to twin registry included 247 pairs cloned the gene ob that encodes normal. The exceptions were two of identical twins — 154 pairs leptin.4 In the years since, tens of inmates who gained weight that had been raised together thousands of articles have been swiftly and effortlessly but then and 93 pairs that had been ad- published on leptin and related struggled to lose that weight opted by different parents. The subjects, such as the hunger- even after caloric consumption identical twins, it turned out, stimulating hormone ghrelin, was reduced. That both these had virtually the same weight re- interactions between these two men had family histories of obe- gardless of whether they had hormones and the neurotransmit- sity added empirical support to grown up together or separately. ter neuropeptide Y, and the sig- the notion that overweight could As reported in another article in naling pathways of molecules in- be heritable. the same issue of the Journal, volved in appetite and the genetic In 1986, the University of Penn- Claude Bouchard and colleagues mutations that might interfere sylvania’s Albert Stunkard offered at Laval University in Quebec had with these pathways. the most compelling evidence yet followed the effects of overfeed- Today, molecular genetics is that one’s weight could be largely ing on 12 pairs of adult, male central to obesity research. In determined by one’s parentage identical twins over a period of 2007, Mark McCarthy, Andrew (1986). Stunkard and colleagues 100 days (1990a).