George A. Bray, MD: Progress inObesitydMultidisciplinaryResearch, Multidimensional ManDiabetes Care 2016;39:1481–1485 | DOI: 10.2337/dc16-1375

FORMATIVE YEARS: INTIMATIONSOF WHAT IS TO COME

George A. Bray was born 25 July 1931in Winnetka, IL, during the peak of theDepression. He was the first child ofGeorge August and Mary H. Bray. Hisonly sibling, Mary Elizabeth (Betsy)Bray, died secondary to rheumatic heartdisease. Influenced by his mother,George developed a natural interest ineducation at a young age, even thoughone of his teachers at Hubbard WoodsSchool in Winnetka reported that11-year-old “George is doing good aver-age work in all subjects” (1). Despite thisinauspicious assessment, high schoolmarked the emergence of a lifelong in-terest in and aptitude for science. This isclearly evidenced by his own writing in1949 in an application for a nationalcollege scholarship program when hewrote: “Ever since I took my first sciencecourse in high school, I’ve been inter-ested in the infinite possibilities of sci-ence.” When it came time to choose acollege, George’s choice between Har-vard and Brown University was basedon the desire to attend one for collegeand the other for medical school. Choos-ing Brown University for undergraduateschool was to have lifelong implications,as it was at the freshman mixer at Brownthat he met his current wife, Mitzi. How-ever, the budding romance was inter-rupted during their sophomore year;they would not meet again until their

25th class reunion in 1978. They havebeen virtually inseparable since. Theymarried in 1982 and have shared a life-time of traveling the world together, see-ing places only known to Ripley of“believe it or not” fame. George has trulyshared his science with the world.

College gave George his first taste ofresearch, measuring the optical rotationof synthetic organic compounds. He

furthered his interest in summer jobsat G.D. Searle in Skokie, IL. He grad-uated summa cum laude from BrownUniversity in 1953, and 4 years later re-ceived his M.D. from Harvard MedicalSchool magna cum laude. His internshipon the Osler service of the Johns Hop-kins Hospital exposed him to the pre-cepts of Sir William Osler (1849–1919)and stirred George’s continuing interestin the history of medicine. Osler hadmused that “no bubble is so iridescentor floats longer than that blown by thesuccessful teacher.” Osler was prescient

George as a child. Who would have known thenthe impact he would make on the world of thescience of obesity?

George at the end of his tenure as executivedirector of Pennington Biomedical ResearchCenter.

1Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA2Morsani College of Medicine, University of South Florida, Tampa, FL

Corresponding author: Donna H. Ryan, ryandh@pbrc.edu.

© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,and the work is not altered. More information is available at http://diabetesjournals.org/site/license.

Donna H. Ryan,1 Barbara C. Hansen,2 and

William T. Cefalu1

Diabetes Care Volume 39, September 2016 1481

PROFILES

INPROGRESS

about his own role in the launch ofyoung George when he said that “thegood physician treats the disease; thegreat physician treats the patient whohas the disease.” This concept was car-ried forth with great commitment byGeorge. George has had a lifetime inter-est in history. His series of articles on thehistory of obesity, originally published

in Obesity Research, has recently beenpublished as a single volume (2). Follow-ing his internship at Johns Hopkins Hos-pital, he entered the U.S. Public HealthService and spent 2 years at the NationalInstitutes of Health (NIH) investigatingrenal physiology. It was here that hepublished his article on “Bray’s Solution,”a cocktail for determining radioactivityin aqueous solutions (3). This is one of hismost highly cited articles and meriteda “Classics” review by the Institute ofScientific Information.

The NIH years not only solidified achoice to pursue a research career butalso led to his marriage to MarthaBardenhagen (1933–2005), a nurse hemet during his year as an intern at JohnsHopkins Hospital. George completed amedical residency at the Strong Memo-rial Hospital of the University of Roches-ter in Rochester, NY, and then began anendocrine fellowship in Rochester. Thisperiodwasmarked by the birth of GeorgeHamilton Bray (1961–1990), the first ofGeorge and Martha’s four children(Thomas Luther, Susan Bardenhagen, andNancy Sylvester Bray).

George’s research training continuedwith work in thyroid hormone and thesympathetic nervous system in a 1-yearfellowship in London, U.K., with Dr.Rosalind V. Pitt-Rivers, the discovererof T3 (triiodothyronine). A second post-doctoral fellowship in thyroid researchfollowedwithDr. Edwin Bennett Astwood

at the New England Medical Center inBoston, MA. It was Astwood who fate-fully set George on his quest to under-stand the biologic underpinnings ofobesity. As George described, the timewith Astwood was when his “directionalsails were set and obesity was the com-pass heading.”

THE FIRST 25 SCHOLARLY YEARS(1964–1989)

George began an academic career as anassistant professor of medicine at TuftsUniversity School of Medicine and as as-sistant physician at New England Medi-cal Center Hospitals in Boston. TheZucker fatty rat had just been identifiedin 1963, and Astwood had the only otherstock other than the ones in the Zuckerlaboratory. In addition to his thyroidstudies, George began his initial experi-mental work in obesity by comparingthese animals with other models ofobesity, including animals with hypotha-lamic injury and animals with a form ofobesity experimentally induced by thefeeding of a very high-fat diet. One ofthe defining aspects of his approach toresearch has been to proceed simulta-neously onboth basic and clinical researchfronts. So, in many ways he did “transla-tional” research before it became fashion-able! For his clinical work in this period, hestudied patients who became obese dueto hypothalamic disease (4) and patientswho became obese because of the inher-itance of the Prader-Willi syndrome (5).

In a move to Harbor-UCLA MedicalCenter in Torrance, CA, George wasaccompanied by post-doctoral fellowDavid York, PhD, who had also been aresearch fellow with George in Bostonin 1969. David and George continued tocollaborate over the years, including ex-changing sabbaticals. David was the firstscientist George recruited to the Pen-nington Center in 1989. They enjoyed along personal friendship, and their ex-tensive collaboration produced manydiscoveries at the bench and in rodentmodels.Most notably, their animal studiesled to the publication of “Hypothalamicand Genetic Obesity in ExperimentalAnimals: An Autonomic and EndocrineHypothesis” (6), which was then fol-lowed by numerous experiments thatsupported this hypothesis. During theirtime together at the Pennington Center,they showed the essential role of gluco-corticoids in the development of obesity,

As Mitzi watches, George receives a commemorative plaque from Dr. Claude Bouchard (executivedirector after George) during a 20th anniversary celebration event for Pennington BiomedicalResearch Center.

In gratitude and acknowledgment for his work andcontributions, and for always doing things the“George Bray way,” Pennington Biomedical namedthe walkway between the basic and clinical researchbuildingsBray’s “Weigh” in his honoron theoccasionof his retirement from the center on 10 December2014.

1482 Profiles in Progress Diabetes Care Volume 39, September 2016

didmuch to aid our understanding of thesystemsdboth central and peripheraldthat regulate the intake of dietary fat,and enhanced our knowledge of themetabolic and endocrine differences be-tween animals susceptible and resistantto obesity. Dr. David York was the leaderof basic science research at Penningtonfor 13 years and was a key contributor tothe success of that effort.George’s research during this period

also had a clinical component. He haddeveloped an interest in overfeedingbased on the work of Dr. Ethan Sims.In anticipation of conducting an over-feeding study, he used himself as an ex-perimental model, going from 165 to190 lbs. As with all overfeeding studies,at the end of the experiment his weightslid back down to 165 lbs. and remainsthere today.In this period, George fostered and

organized the nascent field and can beconsidered a father of obesity research.He chaired the organizing committeefor the 1973 Fogarty Center Interna-tional Conference on Obesity, held inBethesda, MD, and this set the stage forthe 1st International Congress on Obe-sity (ICO) that was held at the Royal Col-lege of Physicians in London in 1974. Hewas a key organizer of that very success-ful, and first of many, IOC, with over500 attendees said to represent over30 countries. It was a conference thatlaunched the careers of two other youngscientists, John Blundell and BarbaraHansen. The Association for the Studyof Obesity (of the U.K.) was establishedout of those meetings. Alan Howard andGeorge became the founding editors ofthe first (1977) scientific journal devotedto obesity, the International Journal ofObesity, which was established as aquarterly journal. It was an importantevent sharing the year 1977 with twoother events, the 2nd IOC and the 2ndFogarty Center International Conferenceon Obesity, both held in Washington,D.C. In 1982 George and others, in-cluding Marcie Greenwood and WayneCalloway, who chaired and organizedthe NIH-sponsored workshop to ex-plore “The Obesities,” gathered manyof the early leaders in the U.S. in thefield of obesity research to try to sortout whether obesity was one or manydiseases. At that meeting at Vassar Col-lege in Poughkeepsie, NY, George chairedthe organizing committee that was

to develop a plan to establish what be-came the North American Associationfor the Study of Obesity (NAASO, nowcalled The Obesity Society). BarbaraHansen became the first president ofNAASO, and George later became itsfifth president. That effort also led tothe establishment of the official Inter-national Association for the Study ofObesity (IASO) that was formulatedat a meeting in Brighton, England, rep-resenting about a dozen countries withcommitments to obesity research (ofwhich George laterwas to serve as a pres-ident). The first meeting was held in Is-rael. He served 4 years on the AdvisoryCouncil of the National Institute of Dia-betes and Digestive and Kidney Diseases,4 years on the Board of Regents of theAmerican College of Physicians, and 1year as president of the American Societyfor Clinical Nutrition.

BUILDING AN OBESITY RESEARCHCENTER AND CONTINUINGSCHOLARSHIP (1989–2015)

In 1989, George became the executivedirector of the nascent Pennington Bio-medical Research Center at LouisianaState University in Baton Rouge, LA.During his 10 years as its director, itrose to become an internationally rec-ognized nutrition research center with astrong focus on obesity research and en-ergy metabolism. As executive director,he oversaw the growth of the facilityfrom 25 employees and a million dollarbudget to a flourishing research enter-prise with over 70 scientists, 350 em-ployees, and an annual budget of nearly$20million. Today, Pennington Biomed-ical has grown into a research enter-prise with an annual operating budgetof over $62 million per year! Georgerecruited key scientists such as York,who became the first head of basic re-search, leading the Experimental Obe-sity Research Program, and he choseDonna Ryan to lead the center’s firstclinical research team. George andhis growing team also attracted key in-stitutional grants. Although his chiefresponsibility during this period was de-veloping the programs at PenningtonBiomedical, he maintained a basic sci-ence laboratory and led clinical researchprojects. Those basic and clinical activi-ties continued beyond his tenure as anadministrator, when he joined the fac-ulty ranks in 2001 as a Boyd Professor,

Louisiana State University’s highest acade-mic rank.

With unparalleled resources to supportbasic science and clinical research,George led research teams at PenningtonBiomedical that have had a major influ-ence on modern assumptions aboutthe biology of obesity. The first majorstudy in this category was the DietaryApproaches to Stop Hypertension, orDASH, study. Pennington Biomedicaland four other nutrition research lead-ing centers initiated a feeding studythat tested dietary patterns for effectson blood pressure. Given the hypothesisthat magnesium, calcium, potassium,and fiber would have salutatory effectson blood pressure, the study testedincreasing consumption of fruits andvegetables and low-fat dairy productsas sources of these factors. It producedclinically significant reductions of bloodpressure in men and women of all ethnicgroups (9). Because the dietary patterntranslates into an easily understood pub-lic health message, the DASH diet hasbeen considered one of the best dietsin America and is recommended bymost national guidelines.

The power of modest weight loss toproduce health improvement is a majorcontribution to field of clinical treat-ment in obesity. That one does notneed to fully normalize body weighthas huge implications for clinical carein obesity. George has been a leader indeveloping and executing the two land-mark clinical studies in testing the effectof weight loss achieved through life-style intervention. He was the leader ofthe Pennington Biomedical clinical sitein the Diabetes Prevention Program(DPP), which began in 1996 and con-tinues as the Diabetes Prevention Pro-gram Outcome Study (DPPOS). Afterthe first 3.2 years of DPP, the lifestyleintervention reduced the conversionrate from impaired glucose tolerance totype 2 diabetes by 58% and a metformintreatment group had a reduced conver-sion rate of 31% (10). The 10-year out-come data (11) confirmed the durabilityof the initial intervention in reducing thelong-term risk of developing diabetes.

The other landmark study of lifestyleintervention benefitting from George’scontribution and his tenure at PenningtonBiomedical is the Look AHEAD (Ac-tion for Health in Diabetes) trial. Thisstudy recruited over 5,000 people with

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overweight or obesity and diabetes andrandomly assigned them to a diabetessupport condition or an intensive life-style intervention (ILI). At the end ofthe first year the average weight losswas 8.6% for those in the ILI conditioncompared with 0.9% loss in the supportcondition (12). At 4 years, some weighthad been regained (14), and the studywas continued in observation beyondthe 4 years of active intervention. Al-though the study did not show a differ-ence at 10.5 years in the primary endpoint (a composite of cardiovascularevents) between the groups (15), thestudy is notable for documenting thebenefits ofmodest weight loss. For thosein ILI, there were long-term improve-ments in cardiovascular risk factors, gly-cemia, diabetes medication use, andeven conversion to normoglycemia(12–15). Further, the study showedmodest weight loss with lifestyle inter-vention produced improvements insymptoms of obstructive sleep apnea(16), hepatic steatosis (17), quality-of-life measures (18), depression (19),decline in mobility associated with aging(20), urinary incontinence (21,22), sexualfunction (23,24), and cost of medicalcare (25).There has long been great scientific

and popular interest in macronutrientapproaches to dieting that might magi-cally produce and sustain weight loss. Incollaboration with Frank Sacks, MD,from the Harvard School for PublicHealth, George designed and executedthe Preventing Obesity Using Novel Di-etary Strategies (POUNDS LOST) study.This study assessed macronutrient con-tent of the diet on the background of auniform program of behavior modifica-tion and exercise. This study used an in-genious 2 3 2 factorial design tocompare 20% vs. 40% fat and 15% vs.25% protein. Thus the study had theability to compare four levels of carbo-hydrate content (35%, 45%, 55%, and65%). Thiswell-executed study (811 sub-jects with a 2-year completion rate of80%) clearly shows that calories countand that themacronutrient compositionof the diet does not have a measurableeffect on the rate or quantity of weightlost (26). In contrast, adherence to thedietary program was central to predict-ing weight loss (27).Pennington Biomedical’s unsur-

passed metabolic study and clinical

research facilities and U.S. Departmentof Agriculture funding enabled Georgeto pursue his curiosity and interest infactors that influence risk for obesity.On the basis of his early interest in an-imal models that became obese on ahigh-fat diet, he developed studies ask-ing how people adapt, or fail to adapt,to eating a high-fat diet. He showedthat the rate of adaptation to a high-fatdiet was much slower than for a high-carbohydrate diet (28). More important,for thepublic healthperspective,was thatthe rate of adapting to a high-fat dietcould be increased with exercise (29).

George’s early interest in overfeed-ing, which spurred his personal experi-mentation, returned and he executed astudy comparing three groups of indi-viduals who were overfed at a level40% above maintenance requirementsfor 8 weeks with diets varying in proteincontent (5%, 15%, or 25%). The subjectseating the low-protein diet gained sig-nificantly less weight than the subjectsconsuming the 15% or 25% protein di-ets, but the quantity of fat deposited, asdetermined by dual-energy X-ray ab-sorptiometry, was identical. Subjectseating the low-protein diet did not in-crease their resting energy expenditureor body protein stores and the extra cal-ories were stored as fat. Those eatingthe 15% and 25% protein diets increasedtheir resting energy expenditure andstored more protein but less fat. Thesefindings suggest that higher-protein di-ets are associated with less fat storageand that low-protein diets will not spareprotein but will enhance energy storageas fat (30).

During his decade as executive direc-tor at Pennington Biomedical, Georgelaid the foundation for the center’sgrowth trajectory and it became worldrenown. After stepping down from theexecutive director post in 1999, he re-mained an active Pennington Biomedi-cal faculty member, continuing to makemany seminal contributions to the fieldof nutrition research, particularly to thearea of obesity. In 2014, he formally re-tired from Pennington Biomedical andLouisiana State University bestowedupon him the rank of Professor Emeritus.

SHOW ME THE BOY AND I WILLSHOW YOU THE MAN

That early teachermay have beenwrongin stating that the 11-year-old George

was “average,” but the teacher did rec-ognize George’s interest and aptitudefor “all subjects.” Indeed, the remark-able attribute of George’s scientific ca-reer is its breadth. His work bridgesmolecule to man to populations. Georgeself-identifies (1) four major themesthat continue to guide his interests, asfollows:

1. A metabolic and endocrine hypothe-sis of obesity (6) that later becameknown as MONA LISA, which standsfor Most Obesities knowN Are Low InSympathetic Activity (31)

2. Responses to overfeeding (28–30)3. The concept that prevention of obe-

sity, similar to the prevention of dentalcaries, might come from the surrep-titious manipulation of environmen-tal factorsdthe FLUORIDE (ForLowering Universal Obesity Rates Im-plement ideas that Don’t demand Ef-fort) hypothesis for the preventionof obesity (32)

4. Changes in the content of sucroseand fructose in the food supply aspotential environmental drivers ofobesity and its complications (33)

These self-described interests, someof which remain hypothetical and de-mand further study, speak to George’sbroad and comprehensive knowledge ofbody weight regulation and its dysregu-lation and enable him to creatively ex-plore discovery from bench to bedsideto populations.

Certainly no man is merely his curric-ulum vitae. George’s finest qualities arenot listed in that document, though itdoes reflect thosequalitiesdperseverance,civility, industry, optimism, curiosity, andcreativity. His success is not based solelyon his scientific acumen but also on hissocial skills and ability to mentor and topromote the careers of his collabora-tors. A cadre of mentees (Donna Ryan,David York, Steven Smith, Ken Fujioka,Frank Greenway, Richard Atkinson, andJennifer Lovejoy, among others) have es-tablished successful independent ca-reers. Long-time collaborators such asBarbara Hansen, Richard Bergman, andFrank Sacks are not just colleagues butfriends.

In his free time, George loves adven-ture travel (to most of the countries ofthe world), theater (for which he has ascholarly and intense appreciation), and

1484 Profiles in Progress Diabetes Care Volume 39, September 2016

his large and growing family (betweenhis children and Mitzi’s five children,Timothy, Bradley, Clinton, Sally, andWilliam, together they currently have16 grandchildren). These enriching as-pects of his life create qualities thatare more than his singular scientific abil-ities. This multidimensional aspect of hischaracter is what made him capable ofshaping the field of obesity inquiry.Throughout his career he has been anadvocate for patients and an early ex-plorer of the biology that underlies theirstruggle with excess body weight and itsconsequences. His impact on the field ismeasurable in leading to the current un-derstanding that obesity is a disease tobe taken seriously.One of the major characteristics of

George is his calming effect on others andhis clear direction of the science. Whileguiding the research at Pennington,it was well known that the study wasbest conducted “George’s way!” Inter-estingly, it also became apparent thatGeorge took the same path every dayfrom his office to the basic and adminis-trative buildings at Pennington Biomed-ical. Thus, the path became known as“George’s way,” and on his retire-ment, and due to his work in a lifetimeof obesity, there was a play on words,and the path is now dedicated toGeorge with a permanent plaque dis-tinguishing it as Bray’s “Weigh.” Asyou can see, the boy in George hasnot changed, but he changed obesityforever.

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