PROFILE PROFILE Profile of Janet Hemingway Ann Griswold grandfather worked in the mines. At around Science Writer age five, Hemingway’s grandfather presented her with a pair of retired “pit” ponies that had pulled coal trucks in the mine but had Asthewheelsofabiplaneapproachadesolate resistance, and helped develop life-saving never been ridden. “I was kind of plopped airfield in the Solomon Islands, a man wear- quinolone antimalarial drugs (1). In her In- on top of one, and off we went,” she recalls. ing only a loincloth breaks through the brush, augural Article (2), Hemingway explores Much of the next few years was spent brandishing a spear and a flail. From behind the increasing challenge of re- outdoors “running riot” with ponies Cap- the plane’s windows four biologists watch sistance in gambiae and Anoph- tain and Blaze, a Labrador-sheep dog cross with wary eyes and silently map an escape eles funestus mosquitoes, vectors named Rinty, and a growing menagerie of route. “You’re thinking, ‘What am I sup- prevalent in the southern African country birds, frogs, and animals that family and posed to do here?’” recalls Janet Hemingway, fi of Malawi. The ndings reveal that pyreth- neighbors left in her care. “It was every Director of the Liverpool School of Tropical roids, the most effective antimalarial insec- girl’s dream, I suppose, trying to sort out Medicine, International Director of the Joint ticides known to date, are under siege by Centre for Infectious Disease Research, and these two little ponies and everything re- resistant variants of Anopheles, and in- lated to animals and the outdoors.” a recently elected member of the National creased monitoring in the impoverished “ Soon, Hemingway’s family moved and Academy of Sciences. And then you realize country is desperately needed to track the this is a welcoming committee.” she transferred from a large comprehen- underlying mechanisms of resistance be- sive school to a small, all-girl grammar Throughout her career, Hemingway has fore malaria regains a stronghold. tackled the problem of malaria transmission school. Although Hemingway passed the from many perspectives: She has worked A Rebel with Just Cause requisite examinations, the new headmis- shoulder-to-shoulder with villagers in trop- Hemingwaywasbornin1957toaworking- tress disliked her previous placement and ical countries, performed basic research in class family in the small coal-mining town objected to her admission. Despite her ob- molecular biology and biochemistry, uncov- of West Yorkshire, United Kingdom. Her vious bent toward biology and genetics, all ered countless mechanisms of insecticide parents owned a corner shop and her of the science classes were full by the time she enrolled, and so she studied the arts. Hemingway plodded through her course- work, determined to do just well enough to get by. Around the age of 16, Hemingway con- templated becoming a veterinarian, although no one in her family had attended college. “When I went to the headmistress and told her I wanted to stay in school, she laughed because she didn’tthinkIwasgoingto get through my exams,” Hemingway recalls. “She hadn’t worked out that I was actually bright.” Against resistance from the head- mistress, who objected to girls pursuing sci- ence, Hemingway switched her studies to gain the advanced-level courses required for college admission. “Ipickedbiology—which felt a bit like falling off a bus, it was so easy— and chemistry, which I had never done be- fore.” Options for the third required subject were limited, though, and Hemingway settled for the unusual combination of biology, chemistry, and religious studies. Ultimately, the coursework did not satisfy the require- ments for veterinary school and was not deemed rigorous enough for most univer- sities in the United Kingdom, but it afforded

This is a Profile of a recently elected member of the National Academy of Sciences to accompany the member’s Inaugural Article Janet Hemingway. Photo courtesy of McCoy Wynne Photography. on page 19063 in issue 47 of volume 109.

www.pnas.org/cgi/doi/10.1073/pnas.1302101110 PNAS Early Edition | 1of3 Downloaded by guest on September 27, 2021 at least one option: admission to an un- offer. “About an hour after he’drung,allthe well as projects in Cambodia, Mozambique, dergraduate program in zoology and ge- rest of them rang, but by that point I’d Mexico, South Africa, Sri Lanka, Thailand, netics at the University of Sheffield (South already said yes to George.” Equatorial Guinea, and the United States. In Yorkshire, England). recent years, data from these ongoing col- During her second year at the university, To the Tropics laborations allowed Hemingway to collabo- days after selecting a thesis project on fruit At the London School, Hemingway studied rate with others to create a comprehensive fly genetics from a list of approved topics, the biochemistry and genetics of insecticide world map of the major mosquito vectors of Hemingway attended a guest lecture on resistance in Anopheles mosquitoes, the pri- malaria, overlaid with climate data to reveal malaria control by Graham White from the mary transmitters of the Plasmodium falci- the geographic boundaries for each species parum protozoan, which causes malaria. British Museum of Natural History. “Once (7). Hemingway hopes the map will serve as Her project characterized the genetics of re- a rebel, always a rebel,” Hemingway recalls. a community resource for regions where sistance to pyrethroids and other “I thought, why bother doing something on malaria is endemic. in various species of mosquitoes (3). She Drosophila when I can go and work on these During her travels, Hemingway recognized completed her doctorate in less than two mosquitoes?” Hemingway broke the news the need for stronger action on the public years and was soon en route across the At- to her zoology and genetics advisors, who health front. In the 1980s, she worked with lantic in pursuit of a postdoctoral program. studied octopus behavior and Drosophila the Industrial Insecticide Resistance Action Hemingway joined the laboratory of George genetics, that she wanted to switch to a topic Committee, the National Malaria Control Georgiou at the University of California at of her own making: one that ventured into Program, and a local research center in Riverside, and continued her studies on the new territory for the university. Chiapas, Mexico to establish the world’s biochemical mechanisms used by insects With their approval, Hemingway asked first large-scale resistance management to evade organophosphate and carbamate White for help in establishing the university’s program to test the long-term public health insecticides, as well as the use of supple- first mosquito insectary. Not everyone was effects of insecticide application models. mentary chemicals to combat the growing pleased, however. The building’s janitor Since 1985, Hemingway has been a stand- problem of resistance (4, 5). was accustomed to mopping the floors ing member of the World Health Organ- In 1984, Hemingway was awarded a Medi- ization’s Expert Committee on Insecticides around the innocuous Drosophila cages in cal Research Fellowship and returned to other laboratories, but Hemingway’smos- and Insecticide Resistance. To urge the London. Hemingway also received a presti- development of additional insecticides and quitoes were another story. The mosquito gious 10-year Royal Society Junior Research larvae were kept in plastic bowls and transi- antimalarial drugs, she aggressively pur- Fellowship. The award unveiled a new horizon sued relationships with industrial firms. tioned to netted cages when they matured, for Hemingway, allowing her to develop an “ ” Her first partnerships were forged with but the odd one is bound to get out, independent research base in London while “ Sumitomo Chemical Company and Well- Hemingway says. I was forever apologiz- traveling extensively and establishing research ing because usually the mosquitoes like come Industries, Ltd, and she soon tar- collaborations between the ministries of health fi biting early morning and early evening, and geted larger rms, such as Syngenta and various universities in malaria-endemic (formerly Imperial Chemical Industries), the only living thing around at that time regions of the world. “It was just this great ” ’ Novartis, and Bayer. In 1990, Hemingway was the cleaner. The janitor s patience ran adventure, really, that I had set off on—and out when Hemingway decided to study became the sole academic member of the someoneelsewasgoingtopaymetodoit!It Joint Industries Action predatory Toxorhynchites mosquitoes, which sounded like a great career to me.” were about five-times larger than the other Committee, where she served until 2004. Over the next decade, Hemingway lived The following year, she joined vector biol- species and did not bite humans but fed ex- for nearly half a year in each rural village, clusively on the larvae of their prey. “The first ogists Barry Beatty, Tom Scott, and Brian returning to her research base in London for Sharp in founding the Innovative Vector morning after they arrived, the cleaner six months before moving on to the next walked in and just kind of stood there, staring Control Consortium, funded by the Bill country. With time, she became adept at and Melinda Gates Foundation. Over the at the new mosquitoes,” Hemingway recalls. performing biochemical and genetic assays in past eight years Hemingway has served as “And then he said, ‘That’s it!Thosethings fi the eld to explore the enzymes responsible CEO of the consortium and helped stimu- will take a pint of blood if they bite me!’” for insecticide resistance in local mosquito late international industries and academic Despite Hemingway’s reassurance, the janitor ’ populations (6). Throughout Hemingway s researchers, as well as the African and Latin quit on the spot and Hemingway was forced travels, she never ceased to be surprised at American Ministries of Health, to develop to clean the laboratory for the rest of the year. ’ the villagers eagerness and curiosity about new pesticides for malaria and dengue By this time Hemingway was seen as her work. control, as well as products for monitoring a rising star in academic circles. Her work in Over the years, Hemingway has traveled to insecticide resistance in disadvantaged areas. establishing the insectary had spurred close Sri Lanka, Sudan, Thailand, India, and Tan- relationships with many prominent ento- zania. Extended stays in each country affor- Higher Calling mologists in the United Kingdom, and they ded Hemingway a deep understanding of As her fellowship drew to an end in the mid- eagerly awaited her graduation. “About half the complex cultural, economical, political, 1990s, Hemingway accepted a position as the an hour after I heard that I was to receive and environmental issues affecting malaria director of biosciences research at the Uni- a first-class honors degree, the phone rang transmission. By the end of her fellowship, versity of Wales, Cardiff. In accepting the and it was George Davidson from the Lon- Hemingway had blazed an international trail position, Hemingway became the United don School [of Hygiene and Tropical Medi- of productive, often decades-long, research Kingdom’s youngest female professor at the cine]. He said, ‘I hear you just got a first. partnerships between clinicians and ento- time. The new role was both a culture shock Think you’ll come and do a PhD with us?’” mologists. She continues to oversee research and a welcome opportunity, as she was After a brief chat, Hemingway accepted his centers in Malawi, Tanzania, and Ecuador, as tasked with supervising a large department

2of3 | www.pnas.org/cgi/doi/10.1073/pnas.1302101110 Griswold Downloaded by guest on September 27, 2021 PROFILE of several hundred biology and preclinical 230 genes from A. gambiae to identify the largely discouraged when the failed malaria researchers. “I learned a huge amount genes up-regulated in insecticide-resistant eradication efforts of the 1960s steered at- managerially,” she says of the experience, and -susceptible mosquitoes (8). Recently, tention from mosquito control to drug de- which prepared her for her next and most Hemingway helped develop quinolone-based velopment. “There was a whole generation recent career move, one that she made with antimalarial drugs that fight malaria by inhib- of scientists that didn’tgettrainedupatthat the utmost reluctance. iting two key enzymes—NADH:ubiquinone point,” says Hemingway, who herself en- — In 2000, eight years into her term at the oxidoreductase and cytochrome bc1 in the tered the field with a just small cohort of University of Wales, Hemingway was re- respiratory pathway of the P. falciparum vector biologists. “Now that trend has re- ’ cruited to the world s oldest tropical medi- protozoan (2). She previously contributed versed and vector control is back on the cine institution, the Liverpool School of to the A. gambiae and Aedes aegypti mos- agenda, but there are too few of us who can Tropical Medicine. The school was in need of quito genome sequences and recently helped actually service that requirement.” restructuring when Hemingway arrived in map the genome of Culex quinquefasciatus ’ Under her guidance and enthusiasm, the 2001, but she quickly rose to the challenge. (9). Hemingway s current projects include new recruits will head to some of the most “I set the benchmark higher, I think, because the biochemistry of xenobiotic resistance ‘ ’ treacherous regions of the Earth to confront Icameinandsaid, I m expecting this of you, enzymes and various models of mosquito the problem of insect-borne disease. “You but I’m also expecting to do this myself. If control in large-scale operational programs can’t look at malaria eradication if you don’t I can do it and run the institute, then I’mnot based in Mexico and Mozambique. go into some of these dangerous places,” asking too much of you.’” Hemingway gave Hemingway says. “Somebody has to do it; the middle tier of researchers more admin- Passing the Torch somebody has to take these agendas for- istrative involvement and, over the course of In the years before Hemingway retires she hopes to increase the number of researchers ward, because some of these places you just her tenure, raised more than £35 million of fi ’ ” capital funding, tripled the faculty, and dou- studying vector biology, a eld that was can tignore. ble the size of the campus without taking on any debt. Meanwhile, she has raised £33 1 6 million in grant funding to support her own Biagini GA, et al. (2012) Generation of quinolone antimalarials Hemingway J (1983) Biochemical studies on malathion resistance targeting the Plasmodium falciparum mitochondrial respiratory chain in Anopheles arabiensis from Sudan. Trans R Soc Trop Med Hyg “ ’ for the treatment and prophylaxis of malaria. Proc Natl Acad Sci USA research. It sseenasahugesuccessstoryin 77(4):477–480. 109(21):8298–8303. the UK,” she says. “We’re still growing, de- 7 Hay SI, et al. (2010) Developing global maps of the dominant ” 2 Wondji CS, et al. (2012) Impact of pyrethroid resistance on spite the global recession. operational malaria control in Malawi. Proc Natl Acad Sci USA anopheles vectors of human malaria. PLoS Med 7(2):e1000209. 8 fi Hemingway has long favored a multi- 109(47):19063–19070. David JP, et al. (2005) The Anopheles gambiae detoxi cation chip: 3 Hemingway J (1980) Modification of the adult resistance test kit to A highly specific microarray to study metabolic-based insecticide pronged approach to vector control, using – measure knock-down rates.Trans R Soc Trop Med Hyg 74(5):677 679. resistance in malaria vectors. Proc Natl Acad Sci USA 102(11): tools from basic science to fieldwork, a strat- 4 Hemingway J, Davidson G (1983) Resistance to organophosphate 4080–4084. “ ” and carbamate insecticides in Anopheles atroparvus. Parassitologia egy that she calls bench to bush. In a 2005 9 Arensburger P, et al. (2010) Sequencing of Culex quinquefasciatus 25(1):1–8. article in PNAS, Hemingway and others 5 Hemingway J (1983) Add on drugs fight insecticide resistance. establishes a platform for mosquito comparative genomics. Science developed a microarray chip representing New Sci 97(No. 1348):649. 330(6000):86–88.

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