The principle of vaccination is simple: if a person is injected with, or swallows, a tiny amount of a virus – either a dead virus or a weakened live virus – that person will develop antibodies against it. Then, if he or she is exposed in the future to the naturally occurring, disease-causing form of the virus, those antibodies will attack the invader and prevent it from causing disease. As biomedical journalist Meredith Wadman makes clear in her marvellous new book, The Vaccine Race, if the concept is simple, making effective vaccines is anything but straightforward.
Viruses had been known to exist since the early 1890s; in the following half-century, dozens of viruses that caused human diseases, such as rabies, polio and influenza, were identified. Unlike bacteria, which can survive independently outside cells, viruses are ‘obligate parasites’ – they can reproduce only by invading living cells and forcing the machinery of the host to make copies.
The first obstacle to overcome in developing a vaccine to combat, for example, polio was the challenge of obtaining enough of the virus. The breakthrough came when John Enders and his team found that the polio virus could be grown in embryonic tissue, a discovery that earned them the Nobel Prize in Medicine in 1954.
Jonas Salk used the kidney cells of monkeys to make the first polio vaccine. It contained a naturally occurring polio virus that had been killed by formaldehyde. Salk believed that it was essential to use a dead polio virus in the vaccine, as a version of the vaccine using a live virus would have a much higher chance of accidentally inducing polio in inoculated children. Alas, it was soon discovered that many of the cells used to make the polio vaccine harboured a monkey virus called SV40.
Leonard Hayflick, a young scientist working in Philadelphia, was convinced that normal human cells would serve as cleaner, safer vehicles for making antiviral vaccines. Hayflick’s WI-38 cells, which originated in an aborted foetus, were used to make vaccines that have been given to hundreds of millions of people. A copycat group of cells developed using the method that Hayflick pioneered has been used to make an additional six billion vaccines.
WI-38 cells were normal, non-cancerous cells and could easily be infected with many viruses. They became vital in the production of new vaccines. Wadman explains how a tiny ampoule of WI-38 cells can be used to produce twenty million tonnes of cells (some ten sextillion cells), and how those cells, when frozen, stop dividing, though they begin replicating again when they are thawed, even after decades.
‘The chase for new virus vaccines in the 1960s was as hot as today’s quest to unravel the profound mysteries of the human genome,’ explains Wadman. Virology and vaccinology attracted the best and most ambitious medical scientists and they soon targeted rubella, better known as German measles. In 1940, it was noticed during a rubella epidemic in Australia that babies were being born with heart defects and congenital cataracts to mothers who had contracted the virus in pregnancy. It was clear that rubella was ‘a menace to life in the womb’; the story of the race to create a vaccine is the centrepiece of Wadman’s fascinating book. One important player was the virologist Stanley Plotkin, who took on Big Pharma by using WI-38 cells to develop a superior rubella vaccine to ones being developed by other researchers. It is also, says Wadham, ‘about the one-, two- and three-year-old orphans on whom Plotkin tested that vaccine, with the blessing of the archbishop of Philadelphia’.
Wadman doesn’t shy away from some very difficult and unpleasant truths. ‘These pages are full of medical experiments that we find abhorrent today,’ she warns early on. In one experiment doctors withheld a treatment known to fight typhoid fever from patients with the disease to see if they died at faster rates than patients who received the drug. They did. These unregulated, exploitative experiments, often carried out on orphans, prisoners, newborns, people on charity wards and disabled children, have long since ceased in the USA. In 1966, after the publication of a seminal paper by Henry Beecher, a doctor at Harvard Medical School, called ‘Ethics and Clinical Research’, which documented two decades of appalling abuses of human subjects, the US surgeon general told government-funded medical researchers that they would have to obtain the informed consent of research participants from then on, and that an independent ‘committee of associates’ at their hospital or university would have to pre-approve human studies.
The days of the medical scientist as a selfless, salaried public servant were about to give way to the commercialisation of biology. New laws and court rulings allowed biologists to make serious money from their inventions. ‘The changes blurred the once-sacred boundaries between business and biology, and by the early 1980s they were turning some biological scientists into wealthy men,’ writes Wadman as she describes the emergence of the American biotechnology industry in the wake of the Supreme Court ruling of 1980 that patent law encompassed ‘anything under the sun that is made by man’. When Jonas Salk was asked, in 1955, who owned the patent for his polio vaccine, he famously replied, ‘There is no patent. Could you patent the sun?’ Sixty years later, in 2015, there were 394 publicly held US biotech companies, with $117 billion in revenue.
The Vaccine Race bears comparison with Richard Rhodes’s Pulitzer Prize-winning The Making of the Atomic Bomb. I can pay no higher compliment to Meredith Wadman and her fine book.