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First IVF babys 40th birthday: How a tiny girl changed science and the world

In July 1978, "You're the one that I want" from Grease was top of the pops in Australia, women were marching for equal rights in the US, and Louise Joy Brown was born in the United Kingdom.

Weighing in at around 2.5 kilograms, the world's first "test tube baby" was delivered by caesarean section under torchlight — to avoid tipping off the media — in Oldham General Hospital, shortly before midnight on July 25.

The Daily Mail reportedly paid around 325,000 British pounds for her first pictures — but even before The Lovely Louise was introduced to the world, she was famous.

Professor Robert Edwards (L) holds Louise while her mother and Professor Patrick Steptoe look on.

(Getty Images: Keystone)

Nine months earlier, Louise's mother Lesley underwent an experimental procedure trialled by the late Patrick Steptoe, Robert Edwards and Jean Purdy, which became known as in vitro fertilization or IVF.

Growing up, Ms Brown kept in touch with the scientists.

"It sounds weird but they were like grandfather figures … they were sort of a bit older than mum and dad," Ms Brown told the ABC on the anniversary of her 30th birthday in 2008.

"We used to send them birthday cards and they used to send us birthday cards, and whenever we could see each other we would."

Today, millions of babies have been born worldwide using IVF and other advanced reproductive technologies.

"Just to think that I'm the first out of all of them … I think, 'Ooh'," Ms Brown said.

Louise Brown turns 40 today.

(Getty Image: Joe Giddens PA Images)

Assisted reproduction technology is incredibly powerful, said Ainsley Newson, a bioethicist at the University of Sydney.

"It has brought happiness and wish fulfilment to many people over the 40 years it's been in existence," Dr Newson said.

"This anniversary is an opportunity for us to think about how we've come to be where we are, and where we want that to go in the future."

The early days: a time of firsts and fights

At the time of Ms Brown's birth, another team of scientists led by the late Carl Wood was also pioneering IVF on the other side of the world in Melbourne.

Like the UK team, they had been trying for a decade to achieve a successful pregnancy, said Alan Trounson, one of the team members, who was based at Monash University at the time.

"There was some optimism by the scientists, but there was a lot of cynicism from many other scientists that thought this was unlikely to happen and was going to be a problem."

Carl Wood and John Leeton in the early days of IVF.

(Supplied: Alan Trounson.)

Soon after Ms Brown's birth, Australia's first IVF baby, Candice Reed, was born on June 23, 1980.

Both Ms Brown and Ms Reed had been born using the natural ovulation cycle — which is wildly unpredictable.

However, Professor Trounson and his colleagues had other ideas and started trialling fertility drugs to try to control the cycle.

"It worked. Suddenly everything became possible," he said.

Professor Wood's team also pioneered techniques to inject sperm into eggs to overcome male infertility; egg donation resulting in the world's first donor egg pregnancy; and freezing embryos, which resulted in the world's first frozen embryo pregnancy.

"We were lauded for those breakthroughs in those early days," Professor Trounson said.

"And because it was happening mostly in Melbourne around us it was something of a national pride."

IVF pioneer Alan Trounson in the early 1980s.

(Supplied: Alan Trounson)

Polling of community attitudes at the time indicated 60 per cent of people surveyed supported the work, he added.

"But the church and the radical feminist groups were very strongly opposed. This was an area they thought was meddling by science," Professor Trounson said.

Professor Wood's team also drew criticism from some scientists, including Professor Steptoe, about the development of techniques such as egg donation, when the first egg donor pregnancy failed in 1982.

As a result, the Victorian government placed a moratorium on the egg donor program. This was lifted at the end of 1983. Legislation dealing with the birth of children using IVF technology was passed by the state and federal governments over the next two years.

At the same time, the world's first ethics guidelines around IVF and embryo technologies were established in Australia.

"It was a very interesting time, but it established a technology that has been rewarding for many people," Professor Trounson said.

"There's over 10 million births now, so you don't often get a technology delivered in such a rapid and effective way."

The 90s to now: from little things big business grows

Though once experimental, reproductive technologies have become standard medical treatments, changing the lives of heterosexual and same-sex couples and single women.

The average age of women undergoing IVF in Australia in 2015 was 35.8 years. Around 1 in 23 children born in Australia were IVF babies, and more than half were born using frozen embryos.

About 1 in 23 births in Australia are created using assisted reproductive technologies.

(News Online Sydney)

But reproductive technologies continue to pose ethical and legal dilemmas.

Assisted reproduction technology (ART) is a "fantastic mechanism for people to form a family when otherwise it would not be possible," Dr Newson said.

"At the same time, I think the way a lot of the industry ART has developed is problematic."

Globally, the fertility industry is estimated to be worth $4 billion annually. But with the industry gaining commercial momentum, questions have been raised over the cost and success of individual clinics.

The use of add-on technologies, such as "assisted hatching" to break down the coating of the embryo and increase the chance of implantation and live birth rates, is also vexed.

"Often things are being introduced into practice before the evidence is really there to show that they work," Dr Newson said.

Professor Trounson, who has moved on from fertility research into the area of stem cell science at the Hudson Institute, is also concerned about this development.

"I'm not supportive of the sort of high technology and add-ons that they've made," he said.

Genetic diagnosis to 'three person IVF'

Along with the potential to treat infertility in both women and men, assisted reproduction technology has offered the potential to diagnose genetic diseases before eggs are fertilized.

The technology, developed in the 1980s, is offered to people with a family history or a diagnosis of conditions associated with specific genes, such as cystic fibrosis.

"[Pre-implantation genetic diagnosis] was a major step forward," Dr Trounson said.

"You could diagnose genetic disorders in these embryos and so you could sort them for patients that had serious genetic disease. That's replaced a lot of the prenatal diagnoses that involves therapeutic abortion."

In 2016, researchers in the United States went one step further when they announced the birth of a baby boy using "three person IVF", to prevent a rare genetic condition called mitochondrial disease.

Dr John Zhang, who helped pioneer three person IVF.

(Supplied: New Hope Fertility Center)

The technique involves replacing the nucleus of a donor egg cell that has healthy mitochondria with the nucleus of the affected woman. The new combined egg, which contains healthy mitochondria from the donor, is fertilized and implanted in the woman carrying the condition.

To get around regulations surrounding experimentation on embryos in the US, they performed the procedure in Mexico.

Today, the procedure is allowed in countries such as the UK. The technique is still illegal in Australia, but the Senate recently gave cautious support for three person IVF and recommended investigation into changing laws surrounding embryo research.

"The legislation was developed about 15 or so years ago and this technology was not predicted at that point," Dr Newson explained.

There are good reasons to be cautious though, she said.

"If you're going to do something that has a good chance of someone being born at the end, then you need to know what is being done is being done with good evidence behind it," Dr Newson said.

But, she added, it is time to look at a way of regulating technology that allows both flexibility and peace of mind.

"I think we are at the point where we need to revisit how we regulate these technologies to allow us to innovate when it's appropriate to do so," she said.

The future: embryos from skin cells?

The past 40 years have pushed the boundaries of science and ethics, but the next 40 years could be even more transformative if a new technology called in vitro gametogenesis or IVG becomes a reality.

IVG combines IVF technologies with advances in stem cell science.

In 2012, a Nobel Prize was co-awarded to Japanese scientist Shinya Yamanaka who discovered it was possible to reprogram cells.

This means cells such as skin cells or blood cells can be potentially turned into egg and sperm cells.

"They're not exactly the same as embryonic stem cells but very, very close," Professor Trounson explained.

Fibroblasts (skin cells) could be reprogrammed into other types of cells in the future.

(Getty Images: Science Photo Library)

Four years later, Japanese scientist Katsuhiko Hayashi used these so-called induced pluripotent stem cells (iPSC) extracted from skin cells from female mice to produce a clutch of healthy pups.

Dr Hayashi, who can not experiment on human embryos, predicted the technology may be used to produce human eggs in the next 10 years, although he was concerned about the quality of the eggs.

Professor Trounson was also cautiously optimistic.

"The technology is not there yet. [But] we're getting there and eventually it will happen," he said.

But while producing sperm cells might be possible, he predicted producing egg cells might be much harder and require other cells from surrounding tissues to reprogram the skin cell.

"I imagine they'll have a lower viability than the natural egg, an embryo, so you probably have to produce more to get the same outcome," Professor Trounson said.

Dr Newson first looked at the potential impact of IVG technology more than a decade ago.

"This technology could have really powerful implications for people who can't generate their own gametes [egg and sperm cells]," she said.

"For example women who've gone into menopause very early in their lives.

"Similarly it might, subject to safety considerations, be something that same-sex couples may be interested in using."

Because the gametes are created using a person's own cells it could also eliminate the need for egg donation or fertility drugs to stimulate the ovary.

"We know that people value genetic kinship, but is that something we value because we are conditioned to value it?" Dr Newson said.

Professor Trounson said the technique also raises the possibility that a father could be a mother as a man could produce egg cells.

"I'm not very good at producing eggs because I've only got one X chromosome but … you only need one X chromosome in an egg."

Whether or not this technology becomes a reality beyond the lab is yet to be seen.

"I think the reality is we will use some of the technology, but some of it will be too difficult or we will ban it," Dr Trounson said.

Not all technology developed over the past 40 years has made it from use in animals to humans.

"Cloning came and went with Dolly and nobody was cloned. I think everybody was happy about that," he said.

Happy birthday: a time to celebrate and reflect

In 2010, Professor Edwards was awarded a Nobel Prize for his work in IVF. He passed away in 2013.

Professor Steptoe passed away in 1988 before he could be awarded a Nobel Prize, but was acknowledged by the Nobel Prize committee.

Ms Purdy, the nurse who worked alongside Professors Steptoe and Edwards managing the laboratory and patients, passed away in 1985 at the age of 39.

Jean Purdy was an IVF pioneer.

(Supplied: Bourn Hall)

Ms Purdy co-authored 26 papers with Professor Steptoe and Professor Edwards and co-founded the Bourn Hall fertility clinic.

"We were a threesome … [she was] the patient, indomitable helper without whom none of our work would have been possible," Professor Edwards wrote in his autobiography.

Although Ms Purdy developed processes that are still part of IVF treatments today, her role was largely forgotten in the IVF story and the Nobel Prize committee.

Professor Trounson, who met Ms Purdy on several occasions, remembers her as a "shy, gentle person" who was devoted to her work.

"She was the key to a very organized and well-functioning laboratory," he said.

Ms Purdy was the first person to see the cells dividing in the embryo that would become Ms Brown.

Forty years later, she is recognized as an IVF pioneer.

Louise Joy Brown — who now has two children of her own — turns 40 today.

Source: ABC News

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