Professor V. Craig Jordan, CMG, OBE, FMedSci, DSc, PhD

Photograph by Robert Seale

Colleagues will be sorry to learn of the death of Leeds alumnus Professor V. Craig Jordan, the clinical pharmacologist whose finding that non-steroidal anti-oestrogens can act as oestrogen receptor (ER) agonists or antagonists at the body’s different tissue ERs, revolutionized women’s health, from breast cancer treatment to osteoporosis prevention. The following tribute has been contributed by his last PhD student and Leeds alumnus Balkees Abderrahman, MD.

Craig Jordan, discoverer of Selective ER Modulators (SERMs), was the founding father of targeted therapy in cancer. Today, there are 5 FDA-approved SERMs (tamoxifen, raloxifene, toremifene, basedoxifene, ospemiphene) used to treat and/or prevent major conditions in women: from the treatment of all stages of breast cancer, to breast cancer risk reduction, osteoporosis treatment, and menopause symptoms’ alleviation. Yet, when Jordan began his research in the early 1970s, with combination chemotherapy being perceived as the cure to all cancers, his concept of a targeted and gentle cancer therapy was deeply resisted. Worldwide, breast cancer is the second most common cancer, osteoporosis affects at least 200 million women, and menopause symptoms impact roughly 85% of women. Jordan’s SERM discovery has had an enormous influence on the lives of women around the world, as well as, the discovery of other selective nuclear receptor modulators and aromatase inhibitors.

Jordan was born in New Braunfels, Texas in 1947 and educated at Moseley Hall Grammar School, Cheadle. There, he met Charles Bescoby, a biology teacher, who tutored him to get A-level grades, allowed him to use the laboratory to teach university-level biochemistry to other boys, and supported his application to the University of Leeds in West Yorkshire, UK, where he completed a PhD in pharmacology, as a Medical Research Council (MRC) Scholar, on the three dimensional structure of the ER by 1973. Beforehand, Jordan received a Bachelor of Science with Honours Class I, as an Ackroyd Scholar, by the Department of Pharmacology, University of Leeds (1969). In 1985, he received a Doctor of Science by the University of Leeds, for scientific contribution to "The pharmacology of non-steroidal antioestrogens." In 2001, Jordan was awarded an Honorary Doctor of Medicine by the University of Leeds, for humanitarian research in medicine that has improved healthcare. Between 2008-2011, he was Chairman of the Scientific Advisory Board at Leeds Institute of Molecular Medicine.

In parallel with Moseley Hall, Jordan secured a technician position at ICI Pharmaceuticals (later AstraZeneca), Alderley Park, UK. ICI would later support his laboratory at Leeds. While being at Leeds, Jordan was awarded a commission and sent to the Regular Army training course in Nuclear, Biological, and Chemical Warfare Defense. His maternal grandfather was the musketry training officer for the Cheshire Regiment and his mother’s family, the Mottrams, were elite horse archers who protected the Black Prince at the Battle of Poitiers. Jordan was later recruited to the British Army’s Intelligence Corps, becoming the youngest captain in the service. Eventually, he joined the British Special Air Service (SAS) with a personal recommendation by General Sir Michael Rose.

In 1972, ICI Pharmaceuticals lost interest in ICI 46,474 (later tamoxifen) as a contraceptive or advanced breast cancer drug. At the Worcester Foundation for Experimental Biology (WFEB), Massachusetts (1972-74), Jordan established the DMBA rat mammary carcinoma model to evaluate the anti-cancer properties of ICI 46,474. He discovered that tamoxifen worked only on ER-positive breast cancer.

Jordan went back to Leeds (1974-79), where he discovered tamoxifen’s role as an adjuvant therapy for the treatment of early-stage breast cancer after surgery, and chemoprevention agent for the reduction of breast cancer risk in high-risk women. Clinicians Trevor Powles and Bernard Fisher used Jordan’s chemoprevention data to initiate the Royal Marsden and NSABP trials. In 1977, Jordan presented tamoxifen’s long-term adjuvant therapy data, at a meeting in King’s College, Cambridge, which encouraged the attendees Michael Baum and Helen Stewart to initiate the NATO and Scottish trials. The later ATLAS and aTTom trials later showed that 10 years of adjuvant tamoxifen therapy reduces breast cancer mortality by 50%.

In 1977, Jordan discovered tamoxifen’s most potent metabolite, 4-hydroxytamoxifen, due to its hydroxyl. This opened the door for the synthesis of new hydroxyl-containing SERMS: raloxifene, bazedoxifene, and lasofoxifene.

In 1987, Jordan discovered that keoxifene maintained bone density in ovariectomized rats. Jordan’s research was rejected by all osteoporosis journals with the premises that “anti-oestrogens cannot build bone, only oestrogens can”. In 1994, keoxifene was renamed raloxifene by the pharmaceutical industry. In 1999, raloxifene was proven to maintain bone density in the MORE trial. Jordan then Chaired the breast cancer committee evaluating raloxifene for osteoporosis treatment.

Other advancements followed: the world’s only successful transfection of ER into ER-negative breast cancer, pioneering structural and pharmacological studies into ER mutations in tamoxifen-resistant breast cancer, the discovery that ER’s Asp351-to-H12 interaction dictates the co-activator recruitment to the ER:SERM complex and thus the SERM’s oestrogenic or anti-oestrogenic behavior, and establishing the world’s premier collection of patient-representative breast cancer cell lines, which Jordan freely shared with other scientists.

Jordan’s patient-transformative work is reorganized by his election to the National Academy of Sciences (2009) (USA), National Academy of Medicine (2018) (USA), Academy of Medical Sciences (2009) (UK equivalent of NAM), and an Honorary Fellowship of the Royal Society of Medicine (2008) (UK). The British Pharmacological Society and the American Endocrine Society recognized his work with the Sir James Black Award for Contributions to Drug Discovery (2015) and with the Gerald Aurbach Award for Outstanding Translational Research (2018). In 2019, Queen Elizabeth II appointed Jordan Companion of the Most Distinguished Order of St. Michael and St. George (CMG) “for international services to women’s health”. In 1993, He was awarded the Cameron Prize (other recipients include: Alexander Fleming, Marie Curie, and Louis Pasteur).

At Leeds University, Jordan endowed the Jordan Prize in Medicinal Chemistry (1999-2024), Jordan Prize for Leeds University Officer Training Corp (1998–2018), Jordan Scholarship in Pharmacology at Leeds University Medical School (2006-2009), LIMM Jordan Lectures at Leeds University Medical School (2007-2009), the Craig Jordan/PR Radford Prize for the best PhD thesis at the Astbury Institute (2017–2024), the Jordan Scholarship for intercalated science degree for medical students (2020-2024), and the Jordan Scholarship for split-site PhD at the University of Leeds/MD Anderson (2017-2020).

Craig, you dared – as cancer researcher and patient – you won, and women’s health is in your debt for life. Your legacy now lives on as the ultimate alchemist when it came to potential, failure, and contradiction: you turned all of your mentees from humble beginnings into rock stars in academia and the pharmaceutical industry, the failed contraceptive tamoxifen into a blockbuster breast cancer drug, the failed breast cancer drug raloxfiene into a blockbuster osteoporosis drug, and oestrogen from the fuel of breast cancer into its killer (selective oestrogen mimics).