In August 1998 in a laboratory at Case Western Reserve University in Cleveland, Ohio, geneticist Patricia Hunt was researching the impact of ageing on chromosomes, the bundles of DNA and protein in cells.
It was highly technical work, and to the outside world of no great interest. Then she noticed something strange happening to the test mice; something so peculiar and potentially so important that it has been widely reported since. She spotted malformed cells in the control group of mice – the animals used for comparison with the ones that undergo experiments. No experiments had been performed on these mice, yet perplexingly they were showing an "extraordinary increase" in cell failure.
While examining test tubes and other equipment to try to ascertain what might have caused this cell failure, Dr Hunt discovered cracks and bubbles in the plastic of the rodents' cages, caused by the use of an unusually strong detergent. As a result, a chemical had leached out of the plastic, and this, Hunt concluded, was behind the rodents' malformations, which were so striking that Dr Hunt abandoned her original experiment and studied the control mice, instead. The chemical Hunt had identified was Bisphenol A, or BPA, a hormonal substance and, even when injected at low levels into the mice, it reduced the mice's "genetic quality".
"What have lab mice or Bisphenol A got to do with me?" you might ask. The answer is that BPA is one of the commonest chemicals in the world. Since it was discovered that it toughened plastic in the 1950s, the chemical has become embedded in the stuff of everyday life. Every time you make a call on a mobile phone or tap something into a computer, handle a compact disc or sports equipment, put on sunglasses or paint your nails, drink water from your tap or run your tongue against a tooth filling, you may be in contact with BPA.
It is massively used by the food industry. As a transparent resin, it lines food containers on supermarket and kitchen, your kitchen, shelves. Most tinned food and drinks, including household names, are lined with a BPA membrane.
Most controversially of all, it is in baby bottles. Biomonitoring tests show that the chemical – which can leach into humans – is present in more than 90 per cent of people; it is almost certainly in your bloodstream now.
But why the concern?
Because BPA – aka 4,4'-dihydroxy-2,2-diphenylpropane – is an endocrine disruptorsomething which may synthetically mimic hormones, affecting the vital workings of the endocrine system of glands, which release hormones around the body, stimulating everything from puberty and the menopause to hunger cravings, fight or flight responses – and the programmed death of cells which would otherwise grow remorselessly, threatening the development of cancer. Put bluntly, interfering with these processes, some scientists fear, may be causing a public health disaster, and BPA, they believe, may be a factor in the rising incidence of a myriad of human illnesses, such as breast cancer, heart disease and genital birth defects.
Breast Cancer UK and the Cancer Prevention and Education Society are so worried about BPA they are calling for it to be withdrawn from products. Eminent British scientists have concerns, too.
At the end of last year, experts from five universities – London, Plymouth, Reading, Stirling, and Ulster – urged the Government to launch a review of BPA. In a letter to the Health Secretary Andy Burnham, they wrote: "Although there are still some gaps in our knowledge on the health impact of BPA on humans, the major body of scientific research and evidence presented over the last decade strengthens the growing consensus that low-level exposure to BPA has a significant impact on increasing the risks of developing conditions such as cancer, diabetes, impaired brain function and behavioural problems in mammalian laboratory animals."
Mr Burnham didn't reply (an official in the Food Standards Agency did two months later), and efforts to encourage Britain to act have failed. Other countries around the world have, however, not been so slow. A decade ago Japan limited the levels of BPA in tins and has removed it from plastic containers used by children. Canada listed BPA as a toxic chemical and banned it from baby bottles.
The biggest American firms no longer make BPA bottles and their sale has been banned in Chicago, Connecticut, Minnesota and Wisconsin.
And in January, after years of denying a problem, the US Food and Drug Administration (FDA) said it was concerned about BPA's impact on the brain and behaviour of children and agreed to support industry's attempts to remove it from infant feeding products and tinned food.
France's Senate last week voted to ban baby bottles containing BPA.
Britain still takes its lead from a heavily-criticised assessment by the European Food Safety Authority (EFSA), which took a similar approach to the now-revised US position.
Critics talk darkly of a cover-up. Some suspect the same tactics of "misinformation" that big tobacco companies once deployed to muddy the link between smoking and lung cancer.
What is certain is that there has already been a public health disaster involving a synthetic oestrogen like BPA.
On a wintry day in December, the US academic Alan Greene is giving a press conference on BPA to mothering magazines (and The Independent) at the Royal Society of Medicine in London.
In a wood-panelled room hired by Born Free, a maker of BPA-free bottles, Dr Greene – the "Al Gore of parenting" – starts by telling the story of Diethylstilbestrol (DES). He says what happened with this artificial oestrogen could give a disturbing clue to what is in store with BPA.
During the mid-20th century, millions of women worldwide took DES for the prevention of miscarriages. Unfortunately DES did not prevent miscarriages.
"But what physicans said – and it chills me to think this," says Dr Greene, pausing for effect, "was 'what harm could it do?' These women are worrying and they will feel better if we give them this pill.
"There was no benefit but DES continued to be prescribed until 1971 – because at that time daughters born to women using DES were showing up with a rare vaginal cancer. It didn't happen except for in the daughters of women prescribed DES."
Dr Greene, clinical professor of paediatrics at Stanford University School of Medicine, says: "It took decades for anybody to figure this out."
DES mothers have passed on their toxic legacy to their daughters and grandsons in the form of more breast cancer and birth defects.
Some scientists are concerned that BPA has a similar "long latency period". As its production has grown over the past 50 years, so have obesity, heart disease, diabetes and other reproductive and behavioural problems. Breast cancer in Britain, for instance, is up by 80 per cent since the 1970s. Hyperactivity in boys has increased seven-fold in 30 years. Tests suggest sperm counts in industrialised countries have halved in 50 years.
As he hits his stride, Dr Greene makes a stark point. "For all of the illnesses that are rapidly increasing in the last couple of decades and that includes, autism, ADHD, allergies of various kind, cancer, Type II diabetes, high blood pressure, it's not that our genetics have changed, it's the environment that has changed. It's environmental exposures, it's how we eat, it's how we move ... and it's the chemicals in our lives."
He and other critics of BPA freely acknowledge that disorders such as breast cancer have complex epidemiologies: you might get them because of genetics, poor diet, lack of exercise, smoking, or a combination of all of those. But, increasingly, they believe man-made chemicals are playing a significant and avoidable role too.
A group of 38 endocrine experts from around the globe who reviewed 700 scientific papers on BPA in the town of Chapel Hill, North Carolina, three years ago reached this conclusion. In a flinty statement known as the Chapel Hill Consensus, they warned that recent trends in human disease "relate to adverse effects observed in experimental animals exposed to low levels of BPA.
"Specific examples," they wrote, "include the increase in prostate and breast cancer, uro-genital abnormalities, decline in semen quality in men, early onset of puberty in girls, metabolic disorders including insulin-resistant diabetes and obesity, and neuro-behavioral problems such as attention deficit hyperactivity disorder."
Studies suggest BPA most affects hormonally-influenced areas of the body, such as breasts and prostrate, brains and reproductive organs, and that its most powerful impact is on foetuses, babies and young children.
While strong, however, the evidence is not conclusive. Not least because medical ethics forbid the deliberate exposure to humans of a substance suspected of causing harm, even though exposure is routine in everyday life. As a result, there are no laboratory experiments on BPA in humans.
There are around 1,000 studies on animals, and they have found problems time and again.
Yale University, for instance, found that BPA harmed the brains of monkeys at a dose level deemed safe for humans in the US.
Tufts University School of Medicine in Boston found experiments on mice and human data on DES strengthened "the hypothesis that foetal exposure to xeno[synethetic]-oestrogens may be an underlying cause of the increased incidence of breast cancer observed over the last 50 years."
Research has been carried out on humans, to check whether there is a connection between levels of BPA in individuals and ill-health. The results have been remarkable. Toddlers of mothers who had high BPA in their bodies while pregnant were more hyperactive, while workers in factories which handle BPA had far more erectile dysfuncton and other penis problems.
In the biggest study, Peninsula Medical School in Exeter found that people with high levels of BPA were a third more likely to have heart disease.
Professor Fred Vom Saal, an endocrinologist at the University of Missouri, says evidence that BPA badly damages human health is compelling. He warns: "BPA is implicated in a host of diseases that are disrupting the lives of millions of people and costing vast amounts of money to treat. Everyone recognises the complexity of diseases such as cancers of the breast and prostate, metabolic diseases, neurobehavioural abnormalities...
"It is thus stunning that administration of daily doses of BPA to animals that leads to blood levels of BPA, at and below levels found in the average person who is examined anywhere in the world, causes all of these diseases."
How can regulators say BPA is safe?
Not all studies find problems with BPA. Some studies funded by chemicals makers or trade organisations give it a clean bill of health.
The American Chemistry Council (ACA), which represents the £458bn-a-year US chemical industry, says BPA is "one of the most thoroughly tested chemicals".
After the FDA performed its U-turn in January, the ACC said it was "disappointed that some of the recommendations are likely to worry consumers and are not well-founded".
The British Plastics Federation accuses Breast Cancer UK of "misleading" the public.
The industry points to several studies that show BPA is harmless at doses above those experienced by humans. And in this it enjoys the support of traditional toxicologolgy, which assumes that everything can be harmful – in big enough doses. Or as the commonly used phrase goes, "the dose makes the poison".
Confusingly, though, synthetic hormones do not appear to work this way. Independent scientists have found repeatedly that they are active at infinitesimally small doses – parts per billion. They insist US and European regulators have made catastrophically misguided decisions on BPA.
Two years ago the FDA issued its draft assessment before an expert report by another US Government-funded group, the National Toxicology Program, expressed its concern. And this draft assessment, the Journal Sentinel in Milwaukee reported, was written largely by the plastics industry and financially interested parties.
Both US and European regulators have controversially set great store by research carrying the imprimateur of an industry protocol, Good Laboratory Practice. GLP was introduced in the late 1970s to stop drug and other companies fiddling results and sets guidelines on such things as calibration and care of equipment.
Writing in the journal Environmental Health Perspectives, last March, 30 scientists complained that GLP studies were using out-of-date and insensitive equipment to test BPA.
They wrote: "It is of great concern that the US and EU regulatory authorities are willing to accept these industry-funded, antiquated, and flawed studies as proof of the safety of BPA, while rejecting as invalid for regulatory purposes the findings from a very large number of academic and government investigators using 21st century scientific approaches."
In particular, they singled out industry-funded studies carried out by US toxicologist Rochelle Tyl at a private laboratory, RTI International in North Carolina. Dr Tyl's studies were particularly important in convincing regulators of the chemical's safety – but the 30 independent scientists claimed they used "insensitive, out-of-date protocols and assays", such as a feed that had been shown to interfere with responses to xeno-oestrogens, and rodents that had a "puzzling" low response to a control hormone, suggesting they would have been insensitive to BPA.
When asked by The Independent to comment on the criticisms, Dr Tyl rejected them: "The studies we have conducted at RTI International are large multigenerational reproductive toxicity studies with validated end points that are used for health risk assessment," she said. "They were conducted using governmental test guidelines (GLP) and are thoroughly documented ...
"The many smaller studies that raised concerns about the adverse health effects of BPA are basic research studies, which use novel exposure pathways (intravenous or subcutaneous injections, implants, etc) and non-validated endpoints, and are not useful for risk assessment. Most of these studies were short term, with few dose groups and few animals per group."
Dr Tyl added that while she was "100 per cent confident" in her work, these other studies had resulted in "very different outcomes", which was why the US Government was funding additional research.
Professor Vyvyan Howard, professor of Bio-imaging at the University of Belfast, believes there is enough evidence to act against BPA, without waiting for further research.
"We're going to have to act on incomplete data, an absence of absolute certainty," he insisted.
"The question the regulators have to answer is, is the weight enough to make us make the decision? But don't get the idea that they are scientific decisions, they're not. The science is there and they [regulators] make a political decision."
Professor Howard believes man-made substances such as BPA – in homes, offices and the environment – are leaving "an appalling chemical legacy".
The academic, who uses a glass baby bottle and cleans his home with vinegar rather than chemical "witches brews", has a track record of being right. He warned children were being made hyperactive by artificial food colourings two years before the Food Standards Agency banned them.
His researchers found that, when combined, food additives had several times their individual effect, yet regulators had only checked them separately. Professor Howard says there has been very little research on the combination of man-made chemicals, because there are so many permutations.
Some 143,000 chemicals registered for use in the European Union, of which around 30,000 are actively traded – making millions of potentially-harmful combinations.
ChemTrust, a British charity, is concerned about several individual chemicals, including the flame retardants in furniture, carpets and bedding, and perfluorinates which, among other things, repel water from clothing and non-stick cookware.
BPA, however, is at the very top of ChemTrust list, along with phthalates (pronounced thalates).
Phthalates make plastics bendy and rubbery and are present in plastic furniture, shoes, PVC flooring and shower curtains. They have been associated with asthma, allergies, obesity and diabetes. A US study last year found two common phthalates were "feminising" boys' brains and making them less likely to play with cars and trains.
Professor Richard Sharpe, a fertility expert at the Medical Research Council, believes phthalates and other chemicals may be damaging couples' chances of getting pregnant.
In a report for ChemTrust last year, he concluded that the cocktail effect of chemicals in the environment were one of several factors "clearly responsible" for lowering sperm count in the West, and probably caused penis birth defects. As well as harming humans, scientists warn that chemicals are threatening the ecological food chain on which humans ultimately rely. The Chapel Hill scientists found that BPA harmed laboratory fish and wildlife, while a UK study reported problems among otters, polar bears, and antelopes.
To counter the threat of persistent environmental pollution, a UN treaty in 2001 introduced a worldwide ban on a "Dirty Dozen" chemicals, mostly pesticides.
Two years later the EU's Research Commissioner, Philippe Busquin, gave a warning that man-made chemicals were a threat everywhere: "Under certain conditions, we can even be at risk while sitting in our sofa at home, not only while cycling downtown at the rush hour."
His words turned out to be prescient – thousands of Britons received skin rashes while sitting on Chinese sofas lined with a dangerous mould-inhibiting chemical, DMF, for which they last year successfully sued the retailers Argos and Land of Leather.
Europe has become alarmed at the potential for harm of chemicals leaching into our lives. Seven years ago a European Commission study found that, of the highest production volume chemicals, 65 per cent had minimal safety data and a further 21 per cent had none.
To close the knowledge gap, Europe has introduced the Reach directive (Registration, Evaluation, Authorisation and Restriction of CHemicals). Described as the most complex legislation in EU history, Reach may eventually answer some of the problems surrounding chemicals, but, after industry lobbying, individual chemicals may only be fast-tracked for extra testing at the request of a member state. So far, no country has submitted BPA.
ChemTrust's Elizabeth Salter-Green believes that BPA is now so heavily embedded in everyday life that no Government particularly wants to tackle it.
And she suspects industry lobbying may explain why regulatory action has been so slow.
"The companies that make a lot of chemicals are the hydrocarbon [oil] companies," she said.
"They pull hydrocarbons out of the ground and make what they can into petrol or aviation fuel. The bit they can't use they make into synthetic chemicals, BPA, phthalates, whatever. So there's this enormously powerful lobbying machine.
"It's not just the chemicals companies who are lobbying, it's the hydrocarbon companies and in the UK and in the US, and oil companies are among the strongest lobbyists we've got."
Two years ago two scientists in the Journal of the American Medical Association claimed BPA makers were conducting "an aggressive disinformation campaign" using techniques first developed by the lead, vinyl, and tobacco industries to challenge the reliability of findings published by independent scientists.
A spokesman for the UK Petroleum Industry Association said he had "never heard of this issue in all my 12 years of working for UKPIA, so it's never come up on our radar," and declined to comment.
The American Chemistry Council insisted its behaviour was proper. Spokeswoman Kathryn St John said: "Industry periodically meets with government regulators to openly discuss the science on BPA, as do others, such as non-governmental organisations. Government regulators gather input from a wide range of stakeholders through written comments, public meetings and individual stakeholder submissions. The entire process is transparent.
"We make products that are critical to the US economy and to the safety of the food supply – it is important for legislators to understand how their decisions may affect our products, our workers and the nation's supply chain."
Laboratory tests on humans for BPA would solve the debate once and for all. But directly injecting humans with an allegedly harmful substance is not allowed.
Instead, it is flowing through the bloodstreams of billions of people in a vast unregulated global experiment.
There is no scientific consensus. It comes down to who you trust – industry-funded or independent scientists? Are we like the mice in Rochelle Tyl's laboratory – or Patricia Hunt's?