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Sir John Warcup Cornforth Jr.,[1] AC, CBE, FRS, FAA (7 September 1917 – 8 December 2013) was an Australian–British chemist who won the Nobel Prize in Chemistry in 1975 for his work on the stereochemistry of enzyme-catalysed reactions,[2][3] becoming the only Nobel laureate born in New South Wales.[4][5][6]

Cornforth investigated enzymes that catalyse changes in organic compounds, the substrates, by taking the place of hydrogen atoms in a substrate's chains and rings. In his syntheses and descriptions of the structure of various terpenes, olefins, and steroids, Cornforth determined specifically which cluster of hydrogen atoms in a substrate were replaced by an enzyme to effect a given change in the substrate, allowing him to detail the biosynthesis of cholesterol.[7] For this work, he won a share of the Nobel Prize in Chemistry in 1975, alongside co-recipient Vladimir Prelog, and was knighted in 1977.[8]

Early life and family

[edit]

Born in Sydney, Cornforth was the son and the second of four children of English-born, Oxford-educated schoolmaster and teacher John Warcup Cornforth and Hilda Eipper (1887–1969), a granddaughter of pioneering missionary and Presbyterian minister Christopher Eipper. Before her marriage, Eipper had been a maternity nurse.[1][9]

Cornforth was raised in Sydney as well as Armidale, in the north of New South Wales,[10] where he undertook primary school education.[9]

At about 10 years old,[11] Cornforth had noted signs of deafness, which led to a diagnosis of otosclerosis, a disease of the middle ear which causes progressive hearing loss. This left him completely deaf by the age of 20 but also fatefully influenced his career direction away from law, his original intended field of study, and towards chemistry.[12][13] In an interview with Sir Harry Kroto for the Vega Science Trust, Cornforth explained:

I had to find something in which the loss of hearing would not be too severe a handicap...I chose chemistry...The most liberating thing was the realization that the literature wasn't entirely correct. It gave me quite a shock at first, and then a thrill. Because I can set this right![14]

Education

[edit]

Cornforth was educated at Sydney Boys' High School, where he excelled academically, passed tests in English, mathematics, science, French, Greek, and Latin,[15] and was inspired by his chemistry teacher, Leonard ("Len") Basser,[16][17] to change his career directions from law to chemistry.[11][18] Cornforth graduated as the dux of the class of 1933 at Sydney Boys' High School, at the age of 16.[19]

In 1934, Cornforth matriculated and studied at the University of Sydney,[19][20] where he studied organic chemistry at the University of Sydney's School of Chemistry and from which he graduated with a Bachelor of Science with First-Class Honours and the University Medal in 1937.[8][21] During his studies, his hearing became progressively worse, thus making listening to lectures difficult.[22] At the time, he could not use hearing aids as the sound became distorted, and he did not significantly use lip reading.[citation needed]

While studying at the University of Sydney, Cornforth met his future wife, fellow chemist and scientific collaborator, Rita Harradence.[23][24] Harradence was a graduate of St George Girls High School[23][24] and a distinguished academic achiever[9][25][26] who had topped the state in Chemistry in the New South Wales Leaving Certificate Examination.[27] Harradence graduated with a Bachelor of Science with First-Class Honours and the University Medal in Organic Chemistry in 1936, a year ahead of Cornforth.[28] Harradence also graduated with a MSc in 1937,[29] writing a master's thesis titled "Attempts to synthesise the pyridine analogue of vitamin B1".[30]

In 1939, Cornforth and Harradence, independently of each other, each won one of two Science Research Scholarships (the 1851 Research Fellowship) from the Royal Commission for the Exhibition of 1851,[31] tenable overseas for two years.[28] At the University of Oxford, Harradence was a member of Somerville College while Cornforth was at St. Catherine's College[32] and they worked with Sir Robert Robinson, with whom they collaborated for 14 years.[9] During his time at Oxford, Cornforth found working for and with Robinson stimulating, and the two often deliberated to no end until one had a cogent case against the other's counterargument.[33] In 1941, Cornforth and Harradence both graduated with a D.Phil. in Organic Chemistry.[34][35] At the time, there were no institutions or facilities at which a PhD in chemistry could be done in Australia.[36]

Career

[edit]

After his arrival at Oxford and during World War II, Cornforth significantly influenced the work on penicillin, particularly in purifying and concentrating it. Penicillin is usually very unstable in its crude form; as a consequence of this, researchers at the time were building upon Howard Florey's work on the drug. In 1940, Cornforth and other chemists measured the yield of penicillin in arbitrary units to understand the conditions that favoured penicillin production and activity, and he contributed to the writing of The Chemistry of Penicillin.[37]

In 1946, the Cornforths, who had by now married, left Oxford and joined the Medical Research Council (MRC), working at the National Institute for Medical Research (NIMR), where they continued on earlier work in synthesising sterols, including cholesterol. The Cornforths' collaboration with Robinson continued and flourished. In 1951, they completed, simultaneously with Robert Burns Woodward[citation needed], the first total synthesis of the non-aromatic steroids. At the NIMR, Cornforth collaborated with numerous biological scientists, including George Popják,[38] with whom he shared an interest in cholesterol. Together, they received the Davy Medal in 1968 in recognition of their distinguished joint work on the elucidation of the biosynthetic pathway to polyisoprenoids and steroids.

While working at the MRC, Cornforth was appointed a professor at the University of Warwick and was employed there from 1965 to 1971.[39]

In 1975, Cornforth was awarded a share of the Nobel Prize in Chemistry, alongside Vladimir Prelog. In his acceptance speech, Cornforth said:

Throughout my scientific career my wife has been my most constant collaborator. Her experimental skill made major contributions to the work; she has eased for me beyond measure the difficulties of communication that accompany deafness; her encouragement and fortitude have been my strongest support.[40]

Also in 1975, he moved to the University of Sussex in Brighton as a Royal Society Research Professor.[10][41] Cornforth remained there as a professor and was active in research until his death.[42][43]

Personal life

[edit]

In 1941, the year in which they graduated from the University of Oxford, Cornforth married Rita Harriet Harradence (b. 1915),[3][23][44] with whom he had one son, John, and two daughters, Brenda and Philippa.[1][45] Cornforth had met Harradence after she had broken a Claisen flask in their second year at the University of Sydney; Cornforth, with his expertise of glassblowing and the use of a blowpipe, mended the break.[46] Rita Cornforth died on 6 November 2012,[47] at home with her family around her,[48] following a long illness.[49]

On an important author or paper that was integral to his success, Cornforth stated that he was particularly impressed by the works of German chemist Hermann Emil Fischer.[46]

Cornforth died in Sussex on 8 December 2013.[45][50][51][52] at the age of 96.[53] Cornforth is survived by his three children and four grandchildren.[54] He was a sceptic and an atheist.[55]

Honours and awards

[edit]

Cornforth was named the Australian of the Year in 1975,[56] jointly with Maj. Gen. Alan Stretton.[57] In 1977, Cornforth was recognised by his alma mater, the University of Sydney, with the award of an honorary Doctor of Science.[58][59] Cornforth's other awards and recognitions follow:

Cornforth's certificate of election for the Royal Society reads:

Distinguished as an Organic Chemist of outstanding originality and exceptional experimental skill, particularly in microchemical manipulation. He was the first to attribute the correct constitution to penicillamine and to synthesise the amino-acid. After making significant contributions to the synthesis of penicillin he notably developed the chemistry of the oxazole group and made oxazole itself for the first time.

The important share he took in the total synthesis of androgenic hormones and other steroids is gratefully recognised by all his collaborators in the investigation.

Miscellaneous work on natural products and chemotherapy equally displays individual thought, invention, and superlative technical accomplishment.[60]

[edit]

Cornforth was the focus of a skit on an episode of Comedy Inc., whereby a fictional Who Wants to Be A Millionaire? contestant (played by Genevieve Morris) is asked "Which Australian scientist won the Nobel Prize for Chemistry in 1975?" for the million-dollar question. As it happens, the contestant gleefully claims they are second cousins with Cornforth (despite being nearly 50 years his junior) and knows Cornforth is the answer, confidently rattling off a bunch of highly specific and esoteric facts about Cornforth's life and achievements, all the while the host (a satirical portrayal of Eddie McGuire) stubbornly and continuously stalls her for dramatic effect, asking her for several minutes if she'd like to think about it more to an absurd degree.[65]

On September 7, 2017, Google celebrated his 100th birthday with a Google Doodle.[66]

The Royal Australian Chemical Institute (RACI) honours Cornforth by naming its prize for the best PhD thesis in chemical science completed at an Australian university the Cornforth Medal.[67]

References

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John Cornforth

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John Warcup Cornforth (7 September 1917 – 8 December 2013) was an Australian-born British renowned for his pioneering research on the of enzyme-catalyzed reactions, for which he shared the 1975 with . Despite becoming profoundly deaf due to in his youth, Cornforth overcame significant personal challenges to make groundbreaking contributions to and biochemistry, including the first of non-aromatic steroids and key insights into biosynthesis that influenced the development of modern drugs. Born in Sydney, Australia, as the second of four children to an English-born Oxford graduate father and an Australian mother of German descent, Cornforth displayed early academic promise, attending Sydney Boys' High School and entering the University of Sydney at age 16, where he graduated in 1937 with first-class honors and the university medal in chemistry. In 1939, he secured a prestigious 1851 Exhibition scholarship to study at the University of Oxford under Robert Robinson, where he focused on the chemistry of penicillin and steroids during World War II, contributing to wartime efforts in antibiotic development. After the war, he joined the Medical Research Council in 1946, later co-directing the Milstead Laboratory of Chemical Enzymology with George Popják from 1962 to 1975, and serving as a Royal Society Research Professor at the University of Sussex from 1975 until his retirement. Cornforth's most notable work involved using , particularly with hydrogen isotopes, to elucidate the three-dimensional mechanisms of enzymatic reactions, revealing how enzymes control molecular in the production of vital biomolecules like . His collaborations, including a lifelong partnership with his wife Rita Harradence—whom he met at and married in 1941, and who served as his primary collaborator and lip-reading interpreter—enabled him to continue productive despite his , which began affecting him around age 10 and rendered him completely deaf by his early twenties. Elected a in 1953, Cornforth received numerous honors, including the Davy Medal in 1968, and his legacy endures in the fields of and .

Early life

Birth and family background

John Warcup Cornforth was born on 7 September 1917 in , , as the second of four children in his family. His father, John Warcup Cornforth, was English-born and an Oxford University graduate who worked as a teacher in . His mother, Hilda Eipper (1887–1969), was an Australian nurse of German descent, whose family originated from early settlers in ; she was a granddaughter of Eipper, a pioneering German Lutheran who arrived in in 1832 to establish religious communities among immigrants. The belonged to the , supported by the father's academic profession and the mother's work in , which provided a stable household in Sydney's suburbs during Cornforth's early years. The later relocated to the rural town of in for a period, exposing young Cornforth to both urban and countryside environments that shaped his formative experiences. This setting, influenced by his parents' educational and professional backgrounds, encouraged an early appreciation for intellectual pursuits.

Childhood and onset of deafness

By age 14, Cornforth's interest had extended to improvised experiments in a home , reflecting a precocious engagement with scientific inquiry. Around the age of 10, Cornforth was diagnosed with , a condition affecting the that initiated a gradual . The progression was slow, spanning more than a decade, and left him completely by approximately age 20, though the partial hearing in his early years allowed him to adapt through lip-reading. He relied on this visual method for communication from an early stage, demonstrating resourcefulness in navigating his impairment. Cornforth's personality during this period was marked by determination and independence, traits that enabled him to confront the challenges of his without undue dependence on others. His family played a crucial role in supporting his adaptation, with his mother, Hilda Eipper, a trained nurse, offering encouragement and practical assistance in daily life as his hearing deteriorated. This familial backing helped foster his resilience, ultimately influencing a pivot toward chemistry as a career suited to his strengths.

Education

Secondary schooling

Cornforth attended in from 1929 to 1933. Despite progressive hearing loss from that made classroom participation challenging, he excelled in , sciences, languages, and other subjects. His had initially encouraged a in , hoping he might become a , but his increasing led him to reconsider such verbal professions. During his years, Cornforth became fascinated with chemistry through the influence of his teacher Leonard Basser, who emphasized the subject's sensory elements like crystals, liquids, dyes, and reactions—aspects less dependent on hearing. This sparked a pivot toward chemistry, reinforced by hands-on school science projects that demonstrated its practical appeal. Complementing his schoolwork, Cornforth conducted early experiments using improvised chemistry setups at home starting at age 14, often in his mother's laundry, where he explored with readily available materials. He graduated in 1933 as (top student) of his class at age 16, achieving outstanding marks that secured his admission to the .

University of Sydney

Cornforth enrolled at the in 1933 at the age of 16, having secured a to study chemistry. Despite his progressive , which by then prevented him from hearing lectures, he was drawn to the practical aspects of laboratory work in . He pursued his studies under influential mentors in the School of Chemistry, including additional supervision from lecturers such as Francis Lions and Gordon Hughes, who emphasized heterocyclic chemistry and synthetic methods. In 1937, Cornforth was awarded a (BSc) with first-class honors in , along with the prestigious University Medal for his outstanding performance. This achievement highlighted his early aptitude for synthetic , built through hands-on experimentation that compensated for his auditory challenges. Following , he continued with postgraduate research, culminating in a (MSc) degree in 1938. During his time at , Cornforth marked his entry into formal research with his first publication in 1938, a collaborative paper on the synthesis of coumarono(3,2-b)indole derivatives as part of a series on . Co-authored with Rita Harradence, Gordon K. Hughes, and Francis Lions, it appeared in the Journal and Proceedings of the Royal Society of and demonstrated innovative approaches to fused heterocyclic systems. It was during his undergraduate and postgraduate years that Cornforth first met Rita Harradence, a fellow student who had excelled in her own BSc the previous year; their shared interest in synthesis laid the foundation for a lifelong professional and personal partnership.

Oxford doctoral studies

In 1939, John Cornforth arrived in Oxford on an 1851 Exhibition Scholarship, one of only two awarded that year for overseas study, arriving just weeks before the outbreak of World War II. This prestigious funding enabled him to pursue advanced research in organic chemistry at the University of Oxford, marking a significant transition from his undergraduate and early postgraduate work in Australia to the international forefront of the field. Under the supervision of the eminent organic chemist Sir Robert Robinson at the Dyson Perrins Laboratory, Cornforth focused his doctoral research on the synthesis of analogues of steroid hormones, a challenging area involving the construction of complex polycyclic structures. His work contributed to Robinson's ongoing efforts to develop synthetic routes for biologically important molecules, emphasizing innovative techniques for carbon-carbon bond formation and stereocontrol in multi-step sequences. Cornforth collaborated closely with Robinson's research team, which included other talented chemists, honing methods that advanced the understanding of under constrained conditions. The onset of profoundly affected Cornforth's studies, imposing severe limitations on resources, chemical supplies, and personnel availability amid Britain's wartime priorities. Despite these challenges, he completed his DPhil in 1941 for on the synthesis of compounds related to hormones. During this period, Cornforth married fellow Rita Harradence, also a recipient at , in January 1941; their partnership would later influence his career extensively.

Professional career

Wartime research in

Upon completing his DPhil in , Cornforth continued his research at the Dyson Perrins Laboratory in , shifting focus to the chemical elucidation of penicillin's structure as part of the Allied . Under the direction of Robert Robinson, he applied his expertise in to investigate the antibiotic's molecular framework, proposing early structural hypotheses such as a thiazolidine-oxazolone arrangement, which contributed to the broader debate on its configuration. This work built on collaborative efforts across 's chemistry and departments, integrating chemical analysis with biological testing to advance understanding of penicillin's potency against bacterial infections. Cornforth collaborated closely with British and American scientific teams, including at the Sir William Dunn School of Pathology, to support large-scale penicillin production for military medical use. His group exchanged data through confidential reports submitted to the Council's Committee on Penicillin, facilitating international synthesis strategies that enabled processes in the United States. A key contribution involved developing methods to isolate and synthesize penicillin degradation products, notably identifying D-penicillamine (β,β-dimethylcysteine) as a core fragment, which provided critical insights into the molecule's stability and potential modifications for therapeutic applications. These advancements helped refine purification techniques, ensuring viable supplies for treating wounded soldiers despite initial low yields. The wartime environment imposed severe challenges, including strict secrecy that delayed publications until 1949 and chronic shortages of reagents and equipment in bomb-threatened laboratories. Cornforth's progressive , managed through intensive lip-reading practice, facilitated participation in group discussions, often with assistance from his wife Rita, who interpreted conversations and co-authored analyses. This adaptation allowed him to lead synthetic experiments effectively, though it limited team size and added personal strain amid the high-stakes urgency of the project.

Post-war advancements at Oxford

Following the end of , John Cornforth returned to full-time research in , establishing a dedicated laboratory with his wife Rita at the Medical Research Council's in , while maintaining close collaboration with Robinson's group at Oxford's Dyson Perrins Laboratory. This setup allowed Cornforth to resume independent projects on synthesis, shifting from wartime efforts to more systematic investigations into complex molecular architectures. Rita's continued involvement as a co-researcher and co-author proved essential, contributing to the precision and efficiency of their joint endeavors. Cornforth's post-war efforts centered on total syntheses of terpenes and alkaloids, yielding breakthroughs in constructing intricate carbon skeletons. In 1951, through sustained with Robinson, he achieved the first of a non-aromatic —specifically epiandrosterone—a complex , accomplished simultaneously and independently with Robert B. Woodward's team. This milestone demonstrated innovative use of stereoselective methods for building polycyclic structures, advancing the field of terpenoid chemistry. These syntheses exemplified Cornforth's emphasis on logical, step-efficient routes inspired by biosynthetic pathways, influencing subsequent natural product strategies. In 1953, Cornforth's rising prominence led to his election as a , affirming his leadership in , and he actively mentored emerging researchers in his laboratory, fostering a collaborative environment that emphasized rigorous experimental design. During this era, Cornforth initiated early explorations into biochemical mechanisms, particularly the enzymatic transformations underlying assembly, which laid foundational insights for his later enzymology studies. By partnering with George Popják, he employed to probe —a key pathway—revealing stereospecific hydrogen migrations and setting the stage for understanding enzyme-mediated reactions. These investigations bridged synthetic with , marking a pivotal transition in Cornforth's career toward mechanistic enzymology.

Directorship at NIMR and Sussex

In 1962, following his tenure at the Medical Research Council's (NIMR), John Cornforth and his collaborator George Popják were appointed co-directors of the newly established Milstead Laboratory of Chemical Enzymology, funded by Shell Research Ltd. in , . This role marked a shift toward administrative , where Cornforth assembled interdisciplinary teams of chemists, biochemists, and biologists to investigate mechanisms, particularly in the of reactions involved in . The laboratory provided dedicated facilities for such collaborative efforts, allowing Cornforth to integrate his expertise in stereochemical analysis into broader enzymatic studies. After Popják's departure to the in 1968, Cornforth assumed sole directorship of the Milstead Laboratory, continuing to guide its research programs until 1975. That year, coinciding with his recognition, he transitioned to the as Research Professor, a prestigious position that afforded him autonomy in pursuing synthetic chemistry mimicking while maintaining oversight of ongoing projects. Although formally retiring from the directorship role in 1975, Cornforth balanced his new academic commitments with residual administrative duties at Milstead for a transitional period. Throughout his leadership at Milstead and , Cornforth mentored numerous PhD students and postdoctoral fellows, fostering a collaborative environment that emphasized rigorous experimental techniques and innovative problem-solving; notable among his key collaborators was George Popják, whose joint efforts spanned decades. Even after official retirement at age 65, he remained actively engaged in laboratory work at , supervising project students into his 80s and contributing to syntheses such as the abscisic acid, until health and institutional funding constraints curtailed his efforts in the mid-2000s.

Scientific contributions

Organic synthesis and natural products

John Cornforth's early contributions to centered on the of complex s, particularly non-aromatic s, which served as precursors to important alkaloids and s. In , working in collaboration with Robert Robinson at Oxford University, Cornforth achieved the first of epiandrosterone, a key androgenic and building block, through a multi-step sequence involving ring construction and stereocontrol techniques. This landmark effort, completed concurrently with Robert B. Woodward's independent synthesis, marked a pioneering advancement in constructing the steroid nucleus from simple precursors like 2-methylcyclopentanone, demonstrating efficient carbon-carbon bond formations and functional group manipulations essential for assembly. Building on this foundation, Cornforth developed stereoselective synthetic routes for , leveraging to achieve precise control over molecular architecture and to probe structural integrity. His approach to synthesizing all-trans-, a linear triterpenoid precursor to cyclic natural products, involved stereospecific olefin formation using deuterated reagents to ensure geometric purity, as detailed in a publication. This method not only facilitated the preparation of isotopically pure for further studies but also established general principles for stereocontrolled synthesis applicable to terpenoid frameworks. By incorporating and labels during multi-step condensations, Cornforth elucidated configurational details, enabling the isolation of enantiomerically enriched intermediates critical for complex terpenoid assembly. In the 1950s, Cornforth's papers on cyclization models provided synthetic analogs to investigate the folding and ring-closure mechanisms underlying formation. His 1954 study contributed to understanding stereochemical aspects in related structures, using model compounds to mimic potential biosynthetic folding patterns and demonstrate how isotopic substitution could reveal migration pathways during cyclization. These efforts, including experiments with labeled epoxides, highlighted anti-Markovnikov additions and chair-like transitions in synthetic mimics, influencing subsequent designs for polycyclic s without relying on enzymatic catalysis. Throughout these endeavors, Cornforth's collaboration with his wife, Rita Cornforth, was instrumental in executing intricate multi-step reactions for synthesis. Together, they pioneered asymmetric induction techniques in the construction of chiral centers, achieving the first stereoselective of a key natural product motif in the steroid series via controlled additions and rearrangements. Their joint work on derivatives, including the Cornforth rearrangement, enabled efficient access to heterocyclic components found in alkaloids, as reported in mid-1950s publications. This partnership not only accelerated synthetic efficiency but also laid groundwork for asymmetric methods later applied in broader campaigns.

Stereochemistry in enzymatic reactions

John Cornforth's investigations into the of enzymatic reactions revealed how achieve precise selectivity in catalyzing transformations at prochiral centers, where substrates lack inherent but can yield chiral products through specific hydrogen replacements. Building on Alexander Ogston's 1948 insight that could distinguish between apparently identical groups in symmetric molecules like citrate, Cornforth extended these principles in the , describing how asymmetric enzyme active sites orient substrates to favor one prochiral face over the other. These principles posit that the enzyme's binding pocket imposes a specific topography, ensuring stereospecific attack by reagents like hydride ions or protons, thus converting non-stereogenic reactions into highly selective processes. A cornerstone of Cornforth's approach involved experiments to track stereospecific transfers. Building on the demonstration by Westheimer, Loewus, Vennesland, and colleagues that yeast (ADH) transfers from a specific stereochemical position in and the coenzyme NADH, using and as tracers, Cornforth extended these findings. By synthesizing stereospecifically labeled [1-²H] and monitoring the enzyme's reduction of , they showed that ADH exclusively removes the pro-R from NADH, establishing the enzyme's absolute at the non-chiral C4 position of the ring. Subsequent experiments extended this to other dehydrogenases, confirming that such selectivity arises from the enzyme's rigid geometry, which positions the substrate and coenzyme in a defined orientation. These findings provided experimental validation for the principles, illustrating how enzymes discriminate pro-R and pro-S hydrogens in achiral centers. Cornforth's work culminated in demonstrating in reactions that do not inherently generate stereocenters, such as hydride transfers in metabolic pathways, which underpinned his share of the 1975 . The recognized his elucidation of how enzymes maintain stereochemical integrity in non-stereogenic steps, using isotopic asymmetry to map reaction trajectories without relying on optical activity alone. This was exemplified in studies of reductions where substitution revealed inversion or retention patterns, proving that enzymes treat prochiral positions as if they were chiral due to the active site's asymmetry. Cornforth's methods for probing enzyme mechanisms through stereochemical analysis were summarized in his 1975 Nobel lecture and subsequent reviews, influencing subsequent biocatalytic research.

Biosynthesis of cholesterol and terpenoids

In the 1960s, John Cornforth partnered with George Popják at the (NIMR) and subsequently at the Milstead Laboratory of Chemical Enzymology to investigate the metabolic pathways of and , building on their earlier collaboration. Their experimental approach involved incubating and liver preparations with radiolabeled , enabling them to trace the incorporation of carbon atoms into and subsequent intermediates, thereby mapping the conversion of to through key steps like epoxidation and cyclization. This methodology revealed the precise arrangement of acetate-derived units in the skeleton, confirming the head-to-tail condensation of units in assembly. A pivotal discovery from their joint efforts was the stereospecific folding of epoxide (2,3-oxidosqualene) catalyzed by oxidosqualene cyclase, which adopts a chair-boat-chair-boat conformation to yield with defined . By synthesizing stereospecifically labeled substrates and analyzing the fate of and carbon atoms via degradation techniques, Cornforth and Popják demonstrated that the enzymatic process proceeds via a concerted mechanism, involving stereospecific proton transfers and migrations that eliminate earlier uncertainties about the cyclization pathway. This work established the enzyme's role in enforcing a specific folding pattern, essential for the formation of the tetracyclic framework. Cornforth's contributions to biochemistry resulted in numerous publications, many co-authored with Popják, detailing pathways from mevalonate to and beyond, with a focus on as a critical intermediate in formation. These studies highlighted the sequential demethylations and double-bond migrations transforming into , using to track substituent movements. In the 1970s, Cornforth's experiments at the further resolved longstanding ambiguities in the pathway by employing chiral methyl-labeled acetates and enzymatic resolutions to probe stereochemical outcomes at each step. These investigations clarified the directionality of hydrogen eliminations and methyl migrations in intermediates, confirming the pathway's and integrating stereochemical principles to validate the overall biosynthetic scheme.

Personal life

Marriage and collaboration with Rita

John Warcup Cornforth first met Rita Harriet Harradence during their undergraduate studies at the in the 1930s, where both excelled in . In 1937, they independently won prestigious 1851 Exhibition scholarships to pursue doctoral research at University, marking the beginning of their lifelong professional and personal partnership. Harradence earned her MSc from the University of Sydney in 1937 before completing her DPhil at Oxford in 1941, specializing in . The couple married in Oxford in September 1941, forging a union that integrated their scientific pursuits seamlessly. Rita Cornforth's expertise in experimental complemented her husband's theoretical insights, forming the cornerstone of their collaborative research. Following their marriage, they co-authored over 40 papers, with Rita often executing the intricate syntheses required for their studies on natural products and enzymatic mechanisms. In 1946, upon joining the Medical Research Council's , the couple established a joint where Rita handled the detailed experimental work, such as and compound purification, while John focused on conceptual design and stereochemical analysis. This division of labor enabled groundbreaking advancements in , with Rita's precision ensuring the reliability of their empirical data. Their partnership was one of true equality, with Rita serving not only as a co-researcher but also as an essential collaborator in navigating John's progressive . In his 1975 Nobel lecture, Cornforth explicitly acknowledged Rita's pivotal role, crediting her "patience and great experimental skill" for much of the synthesis underpinning their Nobel-winning work on in enzyme-catalyzed reactions, effectively sharing the recognition in spirit. This enduring collaboration exemplified mutual support, blending their talents to advance over decades.

Family and later years

Cornforth and his wife Rita had three children: a son, John, and two daughters, Brenda and Philippa. The family established their home in during the early years of the couple's marriage and Cornforth's wartime and post-war research there, before relocating to in 1946 upon joining the . In 1962, they moved to in for Cornforth's co-directorship (later sole directorship from 1968) at the Milstead Laboratory of Chemical Enzymology. In 1975, the family moved again to upon Cornforth's appointment as Royal Society Research Professor at the , where they settled for the remainder of their lives. Throughout these career-driven transitions, the children pursued their education within the British school system, with Rita providing essential support in maintaining family stability amid the relocations. Cornforth formally retired from his university position in 1982 at age 65 but remained active in scholarly pursuits for decades afterward. In his later years, he devoted time to personal interests, including , reading , and playing . Following Rita's death in 2012, Cornforth passed away on 8 December 2013 in , , at the age of 96, after a prolonged illness. He was survived by his three children, two grandchildren, and four great-grandchildren.

Impact of deafness on daily life

Cornforth's profound deafness, which began during childhood and progressed to total hearing loss by his early twenties, necessitated significant adaptations in his daily routines and professional interactions. He relied heavily on lip-reading for communication, though he found it challenging with unfamiliar individuals, and increasingly turned to written notes and correspondence to convey and receive information effectively. In laboratory and collaborative settings, his Rita served as an essential intermediary, interpreting spoken discussions during meetings and easing the barriers posed by his . This approach allowed him to maintain active participation without the use of hearing aids, which he avoided due to sound distortion, or , which he did not employ extensively. Professionally, Cornforth's deafness influenced his work habits by steering him toward solitary, visually intensive tasks that minimized reliance on auditory input. Unable to attend lectures, he immersed himself in primary literature and hands-on experimentation, such as for custom lab equipment, fostering a meticulous and independent style that contributed to his groundbreaking contributions in . His determination enabled remarkable success, including the 1975 , despite the slower pace required for verifying details through visual and written means rather than verbal exchanges. He avoided use altogether, opting instead for letters and in-person or written clarifications to ensure accuracy in scientific discourse. In personally, Cornforth emphasized the visual allure of chemistry—such as the structures of crystals and liquids—as a compensating sensory focus that sustained his passion and productivity. His preference for direct engagement with original sources over secondary interpretations underscored a resilient approach, where sharpened his reliance on visual and precise notation to navigate complex ideas. Through these strategies, he not only managed daily challenges but also demonstrated the viability of scientific pursuit for those with profound hearing impairments.

Legacy

Honours and awards

John Cornforth received numerous prestigious honours throughout his career, recognizing his groundbreaking contributions to and . In 1953, he was elected a (FRS), acknowledging his early work on natural products and synthesis. He was appointed Commander of the (CBE) in 1972 for services to . A pivotal recognition came in 1975 when Cornforth was awarded the , shared with , "for his work on the of enzyme-catalyzed reactions." The award ceremony took place on December 10, 1975, at the , where Professor Sture Forsén of the Royal of Sciences presented the prize, highlighting Cornforth's use of isotopic tracers to elucidate the precise mechanisms in biosynthesis from , navigating among 16,384 possible stereochemical pathways. In his Nobel lecture on December 12, titled "Asymmetry and Enzyme Action," Cornforth detailed the principles of molecular asymmetry in biological processes. At the that evening, Cornforth expressed gratitude to the Academy and Foundation, reflecting on the shared pursuit of scientific truth across diverse backgrounds and emphasizing perseverance in uncovering life's molecular secrets. That same year, he was named , jointly with Alan Stretton, celebrating his achievements as an Australian-born scientist. In 1976, the Royal Society awarded Cornforth the Royal Medal for his distinguished contributions to the understanding of mechanisms. He was knighted in 1977, becoming Sir John Warcup Cornforth, in recognition of his services to chemistry. Also in 1977, he was elected a Corresponding Fellow of the Australian Academy of Science (FAA). In 1991, Cornforth was appointed Companion of the (AC) for service to science, particularly in . In 2001, he received the . Cornforth's later honours included the from the Royal Society in 1982, the society's highest accolade, bestowed for his lifetime achievements in advancing knowledge of enzyme stereochemistry and .

Influence on science and accessibility

Cornforth's pioneering research on the of enzyme-catalyzed reactions has profoundly shaped modern , particularly in the realms of and . His elucidation of how enzymes distinguish between molecular mirror images—such as in the of —provided foundational principles for understanding chiral selectivity, enabling the development of targeted therapeutics like drugs that inhibit to lower levels. This work underscored the importance of stereospecific synthesis, influencing contemporary strategies in where enantiopure compounds are prioritized to minimize side effects and enhance efficacy. Cornforth's insights into pathways have informed studies. Beyond his technical contributions, Cornforth's mentorship legacy endures through the scientists he inspired during his tenure as Royal Society Research Professor at the , where he continued guiding researchers until his 90s. His collaborative approach, often involving visual modeling and detailed discussions, fostered a generation of chemists who advanced into academia and industry. This emphasis on rigorous training in stereochemical analysis has rippled through educational programs, promoting interdisciplinary methods that integrate chemistry with biology. Cornforth's personal experience with profound deafness also amplified his influence on accessibility in science, as he advocated for visual and diagrammatic aids to convey complex concepts, compensating for auditory limitations in lectures and collaborations. His reliance on lip-reading and spatial models in stereochemistry research highlighted the need for inclusive teaching tools, such as interactive diagrams and molecular visualizations, which have since become standard in chemistry education to support diverse learners. Post-2013 tributes, following his death, have celebrated him as a deaf role model, inspiring initiatives like the Royal Society's diversity case studies and programs for disabled scientists, emphasizing resilience and systemic accommodations. His publications, including seminal papers on squalene stereochemistry, continue to garner citations exceeding 10,000 collectively by the 2020s, reflecting their ongoing utility in research and pedagogy.

References

  1. https://www.nobelprize.org/prizes/chemistry/1975/cornforth/facts/
  2. https://royalsociety.org/about-us/who-we-are/diversity-inclusion/case-studies/scientists-with-disabilities/john-cornforth/
  3. https://www.nobelprize.org/prizes/chemistry/1975/cornforth/biographical/
  4. https://www.science.org.au/academy-newsletter/australian-academy-science-newsletter-95/obituaries-john-cornforth
  5. https://www.smh.com.au/national/australian-chemist-who-won-nobel-prize-20131220-2zqyt.html
  6. https://www.theguardian.com/science/2014/jan/12/sir-john-cornforth
  7. https://www.nytimes.com/2013/12/20/world/asia/john-w-cornforth-96-nobel-winning-chemist-dies.html
  8. https://www.the-independent.com/news/obituaries/professor-sir-john-cornforth-chemist-who-overcame-profound-deafness-to-win-the-nobel-prize-for-his-work-on-enzymes-and-cholesterol-9100627.html
  9. https://www.telegraph.co.uk/news/obituaries/10547687/Sir-John-Cornforth-obituary.html
  10. https://history.sydneyhigh.school/nodes/browse/?tax=eyJudGlkcyI6W10sInZhbHVlIjpbIlBlb3BsZVxuIl19
  11. https://www.unsw.edu.au/science/about-us/equity-diversity-inclusion/science-history-trail/john-cornforth
  12. https://history.sydneyhigh.school/nodes/view/5295
  13. https://www.publish.csiro.au/ch/fulltext/ch15100
  14. https://www.sydney.edu.au/content/dam/corporate/documents/university-archives/honorary-awards/c/sir-john-warcup-cornforth.pdf
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  19. https://archives.bodleian.ox.ac.uk/repositories/2/archival_objects/65659
  20. https://www.researchgate.net/publication/346404708_Sir_John_Cornforth_Ac_Cbe_Frs_His_Synthetic_Work
  21. https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201401077
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  28. https://www.britannica.com/biography/John-Cornforth
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  41. https://pmc.ncbi.nlm.nih.gov/articles/PMC2680001/
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