Craig Jordan Obituary

In the 1970s, only 40 percent of women with breast cancer could expect to survive 10 years or longer. Today, that number is more than 75 percent. Screening and early diagnosis have played a role, but one of the main reasons for the improvement is the drug tamoxifen, which dramatically reduces the risk of cancer coming back after surgery.

British-American pharmacologist Craig Jordan, who has died aged 76, was the first to show that tamoxifen can stop tumour growth by preventing the female hormone estrogen from attaching to specific sites in the breast called estrogen receptors.

Breast cancer is the most common cancer in women worldwide. 80% of women with this disease have receptors that make them sensitive to estrogen. Estrogen can stimulate the cells in the breast to reproduce uncontrollably and form tumors.

Jordan’s lifelong study of tamoxifen led to the discovery of a series of other effective treatments for breast cancer that either blocked estrogen receptors or reduced the amount of the hormone the body produced. His studies have also improved women’s health by shedding light on other conditions, including uterine cancer, osteoporosis and menopausal symptoms.

He made his discoveries despite enormous skepticism from the medical community. He was not a doctor, but a laboratory scientist who conducted his research on rats and mice. Tamoxifen does not kill cancer cells, it only stops them from growing. The conventional wisdom in the 1970s, when he began his work, was that the only way to treat cancer was to cut it out, or to blast it with radiation or powerful chemicals to destroy every trace of the tumor. Such treatments can be effective, but they are stressful for patients and have many side effects.

“There was this obsession with the idea that this combination of chemotherapies would cure all cancers,” Jordan told the website Oncology Central in 2019. “It felt like we were swimming against the tide, because we were saying, no, target the estrogen receptor and give tamoxifen forever and people will live.”

It took decades for the evidence for tamoxifen’s effectiveness to become undeniable. A few clinical research groups, encouraged by Jordan’s lab results, had tested tamoxifen in patients, but the results, while encouraging, were too marginal to change practice.

In 1998, the Early Breast Cancer Triallists Collaborative Group in Oxford combined data from studies of 37,000 women. It found that women with estrogen-sensitive tumors who took tamoxifen five years after surgery were 47 percent less likely to have their cancer come back and 26 percent less likely to die within 10 years.

Tamoxifen and other selective estrogen receptor modulators are now part of the standard treatment for women who have undergone surgery for estrogen-sensitive breast cancer.

Jordan’s mother, Cynthia Mottram, was a GI bride who met his father, Virgil Johnson, while serving as a private in the U.S. Army in Britain during World War II. They returned to New Braunfels, Texas, where Jordan was born, but the marriage failed and she moved her son back to her home in Cheshire when he was a toddler.

He attended Moseley Hall Grammar School in Cheadle, where he took to chemistry with such enthusiasm that his mother set him up in a laboratory at home (which led to the sort of near-disaster that many successful scientists suffer early in life). After his mother remarried, Craig was adopted by his stepfather, Geoffrey Jordan, and took his name.

Initially his ambitions were limited to working as a technician in the nearby ICI laboratories, but he managed to secure a place at the University of Leeds to study pharmacology. During a summer job at ICI he met the endocrinologist Arthur Walpole, who was part of the team that developed tamoxifen, then known as ICI 46,474.

It was supposed to be a contraceptive, but early trials led to more pregnancies instead of fewer. During his PhD at Leeds, Jordan developed strong ties with the ICI scientists who funded the early stages of his work on oestrogen receptors.

In 1972, Jordan went to the Worcester Foundation for Experimental Biology in Massachusetts. The lab was focused on contraception, but after ICI 46,474 failed as a contraceptive, Jordan began studying its effects on breast cancer in rats. By 1973, ICI had named the drug tamoxifen and launched it as a not-so-effective treatment for late-stage breast cancer.

The following year Jordan returned to Leeds as a lecturer, where he continued to work with ICI. His major discoveries during this period were that tamoxifen, given over a period of years, could be used to prevent cancer from coming back after surgery; and that it could prevent cancer from developing in women whose biology put them at particularly high risk. He also discovered a highly effective breakdown product of tamoxifen that formed the basis for other drugs that prevent bone loss in postmenopausal women.

In 1980, he moved permanently to the US, where he held senior positions at a series of leading research universities, establishing a “tamoxifen team” at each, before settling down permanently in 2014 as professor and chairman of cancer research at the University of Texas MD Anderson Cancer Center in Houston. His further discoveries included a slightly increased risk of uterine cancer with tamoxifen, so that doctors now screen their patients before prescribing the drug.

For much of his life, Jordan had an unusual, parallel career as an advisor on biological and chemical weapons – and illegal drug use – to the British and American militaries.

His family had a strong military background and he had joined the Officers’ Training Corps while a student at Leeds, combining his PhD research with periods with the army in Germany during the Cold War. He was subsequently recruited into the Intelligence Corps with the rank of captain and subsequently joined the SAS reserve. He was a keen collector of antique weapons and described himself as an “excellent shot”.

He received many honours during his career and was appointed CMG in the Queen’s Birthday Honours in 2019 for services to women’s health. In turn, he funded prizes, fellowships and special lectures at the universities of Leeds and Oxford, conscious of the debt he owed to British society for his early education and research opportunities. He was open about his diagnosis of kidney cancer in 2018 and continued to work until shortly before his death.

Craig Jordan was married three times, each marriage ending in divorce. He is survived by Alexandra and Helen, his daughters from his first marriage to Marion Williams, and five grandchildren.