Past and present women pioneers in biomedical science

COVID-19 has propelled a number of scientific breakthroughs that have only been possible because of unprecedented global research collaborations. These remarkable achievements will have profound implications for the future. Women have been front and centre in many of these developments, notably in the area of COVID-19 vaccines and sequencing of SARS-CoV-2. Yet in this pandemic women's position in biomedicine has not been helped by the fact that many women have been disproportionately affected by increased caring responsibilities during lockdowns, reducing the amount of time they have been able to devote to research and publication—with implications for career advancement. As a historian, I have spent many years uncovering the contributions of women to advances in medicine and science, many of whose achievements were overshadowed by their male counterparts. So it is illuminating to mark the scientific achievements of a few of the women involved in the COVID-19 response and also look back to the work of other forgotten female researchers in whose footsteps they tread.

All too often women get ignored because their skills are less highly prized and their discoveries and input are marginalised within the workplace. Historically, women have tended to land up in medical and scientific fields that were traditionally deemed less prestigious but where they had greater freedom to work part-time. Two such areas are vaccines and microbiology. From the 1970s there was a general decline in pharmaceutical companies' involvement in vaccine research, partly connected to an increase in lawsuits against vaccine manufacturers and paucity of government investment. Similarly, clinical microbiology had suffered years of underfunding. In 2003, the UK Government cut funding for the Public Health Laboratory Service, which since 1946 had been one of the country's first lines of defence against public health threats. Over the past three decades, clinical microbiology research in the USA has also been underfunded. One reason for the limited investment in vaccines and microbiology in previous decades was a mistaken belief that infectious diseases no longer posed a threat to public health in high-income countries. Yet both vaccines and microbiology have proven crucial in COVID-19 control. It is in these fields where women have made a visible mark in the pandemic, often after working for many years below the radar.

One such woman is Sarah Gilbert, professor of vaccinology at the Jenner Institute, Oxford University, UK, who, together with colleagues, designed the platform that underpins the AstraZeneca–Oxford ChAdOx1 nCoV-19 vaccine. For more than 20 years, Gilbert has been working with Adrian Hill, director of the Jenner Institute, to create recombinant viral vectors that they believed would make it easier to make vaccines capable of inducing T-cell responses alongside antibody responses, which would enhance their efficacy. The ChAdOx1 nCoV-19 vaccine uses a chimpanzee adenovirus vector to deliver a genetic sequence that codes for the surface spike protein of SARS-CoV-2 to prime the immune system to destroy the coronavirus. Gilbert's research group first started genetically modifying a common cold virus in the 1990s. Patented in 2016, the chimpanzee-derived adenoviral vector provided a platform to rapidly roll out cost-effective vaccines against emerging pathogens and neglected diseases. Before COVID-19, Gilbert's team explored the vector's capability in a number of vaccines, including against influenza, malaria, and the Ebola and Zika viruses. Early stage human trials in 2018 indicated the vector to be safe and effective at promoting an immune response in a vaccine for MERS-CoV.

Despite this impressive track record, like some other female scientists Gilbert once considered giving up her scientific career because of the challenges of balancing the demands of full-time research with her role as a parent to triplets. Yet, as she admits, parenthood prepared her well for coping with the pressures involved in her accelerated research during this pandemic. It taught her how to be highly organised and how to survive on very little sleep. As she puts it, “If you get 4 hours a night with triplets, you're doing very well. I've been through this.” Importantly, her research efforts were helped by the fact she and her team were already immersed in work on pandemic preparedness to create a vaccine against an outbreak of a new disease.

Gilbert's grit is matched by that of Professor Katalin Karikó, whose once dismissed dream to develop mRNA therapeutics to fight disease lies behind the development of the Pfizer–BioNTech and Moderna COVID-19 vaccines. Born in Hungary and trained as a biochemist, Karikó has had more than her fair share of challenges. In 1985, she was made redundant at the age of 30 and forced to seek a new academic life with her husband and young daughter in the USA with little funds to support them. Working in Philadelphia, Karikó experienced 15 years of having grant applications rejected for research on therapeutic applications of mRNA, an area she first started investigating in Hungary. Without grant support for her research, in 1995 Karikó had the demoralising experience of being denied promotion at the University of Pennsylvania, although she had been on the faculty for 6 years. Karikó's struggle partly reflected the fact that her research was seen as too radical because synthetic mRNA can be easily degraded, which made it potentially unsuitable to be a drug. Unwilling to give up on her idea, Karikó's luck changed when, in 1997, she persuaded Drew Weissman, a physician and an immunologist who had just joined the faculty at her institution, to collaborate with her. In 2000 they reported synthetic mRNA to be immunogenic, but in 2005 made a breakthrough: they found that incorporating modified nucleosides into mRNA prevented the immune response. Hardly noticed at the time, their discovery laid a foundation for using mRNA technology for COVID-19 vaccines and Karikó is now a senior vice president at BioNTech.

Fanny Angelina Hesse (1850–1934)

© 2021 GL Archive/Alamy Stock Photo

That technology played a part in the work of another notable researcher. Working persistently to advance her field, from 2014 viral immunologist Kizzmekia Corbett led research into the development of new vaccines for coronaviruses at the US National Institutes of Health (NIH) Vaccine Research Center. Corbett, who grew up in North Carolina, USA, was first drawn to coronaviruses because, as she says, “ironically…most other people were not” and it was a way to “build a niche and to tap into some uncharted territory”. Crucially, Corbett helped to determine that an ideal vaccine target for such viruses was its spike protein. She worked this out with colleagues in 2017 while investigating MERS-CoV. This research laid an important blueprint for the Moderna–NIH mRNA-1273 vaccine that Corbett helped to develop. Corbett had a key role in designing the vaccine and led the preclinical studies needed before it could be tested in humans. She also developed the assays needed for testing clinical trial samples. Corbett also contributed to work on antibody responses to coronaviruses that provided a foundation for the development of the neutralising monoclonal antibody therapy LY-CoV555 for COVID-19.

One of the first generation in her family to attend university, Corbett first developed a curiosity for science aged 16 years, after being selected by a programme for gifted minority students to work as an intern in a chemistry laboratory at the University of North Carolina. Recently appointed Assistant Professor of Immunology and Infectious Diseases at Harvard University, Corbett has written about the importance to her of “‘Each one teach one’, an African American proverb, birthed out of slavery, suggesting it is one's duty to pass knowledge onward to those who are not as privileged.”' Eager to mentor other girls and minority students to follow in her footsteps, Corbett has made contributions in the USA to increasing participation in clinical trials and to the uptake of COVID-19 vaccines among Black communities that have been hit disproportionately by COVID-19.

Just as Corbett was the first in her family to attend university, so too was Sharon Peacock. Professor of public health and microbiology at the University of Cambridge, in March, 2020, Peacock spearheaded the setting up of the COVID-19 Genomics UK Consortium (COG-UK) with colleagues to rapidly sequence as many SARS-CoV-2 viral genomes as possible to map out the spread and evolution of the virus. Discussing COG-UK with me, Peacock is astonished at the speed with which she and others managed to get the ball rolling, at a time when many were initially sceptical that the virus would mutate enough to make the venture worthwhile. Poignantly, she remembers occasions when she thought, “What have I done? What if this is a complete failure…and it's the wrong decision.”

For Peacock “a key defining moment” in her life was when she failed the exam needed to gain entrance to grammar school. This meant she went to a secondary school where more emphasis was placed on practical domestic and secretarial skills than academic subjects, preventing her from taking exams necessary for entering university. Only equipped with a basic training in maths, Peacock left school aged 16 years to start work in a shop and then a year later set about training first as a dental nurse and then a nurse before deciding to pursue a career in medicine. She attained her entry qualifications by going to evening classes and a technical college while working part-time. Peacock eventually secured a place in medical school as a mature student.

Before the pandemic, Peacock had spent a decade determining the value of pathogen sequencing in public health microbiology. This included the use of genomic epidemiology to understand the transmission of health-care-associated infections as well as the relationship between antimicrobial resistance (AMR) in humans, livestock, and the environment. Her experience in this area was a perfect background for COG-UK. Peacock attributes much of the consortium's success to the chemistry and “can do” attitude of the people she managed to get involved. It is also reflective of her own collaborative leadership style that encourages everyone to have an equal voice. From the start she envisioned the consortium should have a clear vision and structure that allowed independent thinkers to work loosely together, maximising on the possible impact of the varied expertise across the membership. Peacock's collaborative approach is refreshing in today's highly competitive world of science.

It also brings to mind some other women from the past who I profiled in an online exhibition about scientists' long efforts to understand and overcome the challenge of AMR. What is striking is how much of the early knowledge generated about the biological mechanisms underpinning AMR rests on women's ingenuity, yet their contributions have been largely forgotten.

The microbiology world, for example, owes a great deal to Fanny Angelina Hesse, known as Lina. It is thanks to her that laboratories now use agar to culture and study microbes. She first suggested the medium as a replacement for gelatin in 1881 while working as an unpaid technician to her husband, Walther Hesse, a medical practitioner and bacteriologist. For many years she coated glass tubes with gelatin for Walther to grow microorganisms, but this was unsatisfactory as the gelatin melted on warm days and could be destroyed by some bacteria. To solve the problem, Lina turned to agar, which she used to prepare preserves and puddings. Agar had several advantages: it remained solid in temperatures up to 90°C, was transparent, could not be digested by microbial enzymes, and could be sterilised and stored for long periods. This meant agar could be used for long-term cultures of bacteria, which was crucial, for example, in research on tuberculosis. A talented artist with a strong understanding of bacteriology and microscopy, she also drew many pictures of magnified colonies of bacteria at different growth phases for her husband's publications. Walther, however, rarely acknowledged her assistance. Lina herself never sought credit. Her contributions only came to light in 1992 when her grandson published a brief biography of Lina and Walther.

Esther Lederberg is another woman largely overshadowed by her husband, Joshua Lederberg. Awarded the Nobel Prize in Physiology or Medicine in 1958 for his discovery that bacteria can exchange genes, Joshua's breakthrough rested considerably on Esther's input, to whom he gave scant acknowledgment when he received the prize. Esther was herself a pioneer in bacterial genetics but never gained a permanent academic position. In 1950 she isolated the lambda phage, a virus that infects Escherichia coli, and in 1953 published work showing that it could insert its own DNA into the genome of infected bacteria. The phage provided an ideal tool to understand the pathways that viruses use to transfer genes into bacterial cells, which is a key mechanism behind AMR. Esther was also pivotal to the development of replica plating. This technique enables scientists to make a perfect copy of the geometric pattern of all bacterial colonies growing on an agar plate. Her method revolutionised the ability to screen bacteria for a desired mutation and to track their mutations. Before her invention, scientists spent many painstaking hours transferring bacteria between petri dishes with blotting paper, toothpicks, or a wire brush. Coming from a family of textile workers, Esther grasped that velvet cloth with the right pile thickness offered a much simpler solution because its dense fibres could act as tiny needles to pick up and transfer the bacterial colonies in one go. By attaching the fabric to a wooden block, Esther showed that it could pick up just enough bacteria from a master agar plate to create identical colonies on other plates. Esther worked for decades at Stanford University, USA, becoming director of its Plasmid Reference Center in 1976. Her innovative work in microbial genetics proved an inspiration for many other researchers.

Esther M Zimmer Lederberg (1922–2006)

© 2021 Esther M Zimmer Lederberg Memorial Website/estherlederberg.com

The pathologist and bacteriologist Mary Barber is another overlooked pioneer. Working at the Hammersmith Hospital in London, UK, Barber was one of the first to document the rise of antibiotic resistance and its role in cross infection in hospitals. An effective mobiliser, she showed that it was possible to reduce drug-resistant staphylococcal infections in hospitals by getting all the hospital staff to adhere to strict hygiene and sterilisation procedures and limiting antibiotics only to patients who would benefit. Predicting in 1950 that antibiotic-resistant staphylococcal infection would soon become an urgent problem, Barber's pioneering measures are an important lesson for today's control of hospital-acquired infections.

The contributions of women during the COVID-19 pandemic and in the past are a powerful reminder of their pioneering roles behind advances in biomedical science. Running throughout the stories of the women featured here is their determination, collaborative approach, and ingenuity, which are vital ingredients to making progress in science and medicine. Productivity, innovation, decision making, and employee retention are enhanced when women are given an equal role in organisations and gender diversity is supported. Institutions that place emphasis on diversity and inclusion also tend to outperform those that do not.

Sarah Gilbert

© 2021 Steve Parsons/PA Wire/PA Images

Katalin Karikó

© 2021 ZUMA Press, Inc/Alamy Stock Photo

Kizzmekia Corbett

© 2021 Tim Nwachukwu/The New York Times via Getty Images

Sharon Peacock