New non-hormonal contraceptive avoids side effects of the Pill

Almost 60 years after the development of the Pill, scientists have announced they are working on the first alternative oral contraceptive, and they hope it will be free of side-effects.

Instead of controlling the woman's monthly cycle, the new drug would work in an entirely different way by targeting a gene that controls female fertility and it would be completely reversible.

Unlike the existing Pill, it would not contain hormones and scientists hope it would have far fewer adverse effects. It could be delivered through a patch on the skin which would need to be worn for only a few days each month, when the woman was ovulating. Women who take the Pill complain of mood swings and nausea and are at higher risk of blood clots and high blood pressure. The Pill contains small doses of the hormones oestrogen and progestogen which block ovulation but cause side-effects.

The new contraceptive, which is in the early stages of development, would avoid these side-effects because it does not depend on manipulating hormones.

Instead it would allow ovulation to occur as normal but would prevent the sperm penetrating the egg by targeting a gene called ZP3. Blocking the gene prevents production of a protein that forms part of the coating of the egg which enables sperm to bind to the outer layer. The technique is based on RNA interference, which targets specific genes.

Dr Zev Williams, of Brigham and Women's Hospital in Boston, presented the findings at the American Society for Reproductive Medicine conference in Washington. He said trials on humans were a decade away and the drug had only been tested in mouse and human kidney cells. But the results had demonstrated "proof of principle" showing that it worked. "Mice that have ZP3 knocked out are infertile. They just don't get pregnant. If you could block this in women, you could prevent pregnancy from occurring. Our work is a proof of concept, in cell culture."

Dr Williams said there were only three kinds of contraceptive – hormones, IUDs and barriers – and there was an obvious need for a wider choice. "Since the 1950s we have had the entire biomolecular revolution in medicine, and yet these three options are still all there is. We simply don't have a contraceptive drug that is non-hormonal and reversible. What we are trying to do is to think about contraception in a new way. Obviously there are going to be big hurdles and it is going to take a lot of time, but the need is there and we think it can be achieved."

Some women derive benefit from the hormonal effects of the Pill because it regulates their monthly cycle or reduces menstrual pain. "But for women who use the Pill just as a contraceptive, a non-hormonal approach would be wonderful," Dr Williams said. "You could get all the benefits without the nausea, the headaches, the mood alterations, and the raised risk of thrombosis, stroke and heart attacks."

Andrew Sharkey, senior research associate in the Department of Pathology at Cambridge University, said: "The advantage of ZP3 is that it doesn't occur anywhere else in the body, so the effect is highly targeted. You can get weight gain with oestrogen and some pills have an effect on libido and mood and every woman has a different response. The oral Pill is nearly 60 years old and there has been no real advance since then."

How the process was discovered

RNA interference – which means, in scientific terms, silencing, or quelling – came about originally through experimentation among plant researchers during the 1990s. Although the aim was to produce darker flowers, what emerged were almost entirely white flowers, less pigmented and – crucially – indicating that 'chalone synthase' had been significantly decreased. It was used on other organisms such as worms and fruit flies, and in 1998 a paper in the journal Nature by the scientists Craig C Mello and Andrew Fire, introduced the concept of gene silencing and they won the Nobel Prize in 2006