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First IVF baby's 40th birthday: How a tiny girl changed science and the world
ABC Science, by Genelle Weule

首位试管婴儿的四十岁生日——一个小小女孩如何改变了科学与世界
本文由吉纳尔·兀勒发表于澳大利亚广播电台网站科学频道



Baby photo of Louise Joy Brown taken not long after she was born.
Louise Brown made headlines even before she was born (Getty Images: Keystone)

上图是在路易斯·乔·布朗出生后不久所拍的照片。 路易斯·布朗甚至在出生之前就上了头条新闻。

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.

1978年的7月, 澳大利亚人正把《搞笑音乐会》(Grease, 又译为《油脂》)里的《你是我想要的人》捧上流行之巅, 美国女人在为平权游行示威, 而英国则迎来了路易斯·乔·布朗的诞生。

就在7月25日的午夜之前, 奥德哈姆综合医院的医生为了躲避媒体的骚扰, 在手电筒光线的照耀下, 以剖腹产的方式接生了这位重达2.5公斤的世界首位试管婴儿。 据说《每日邮报》为她的首张照片支付了大约32.4万英镑的费用——然而在可爱的路易斯被介绍给世界之前, 她就已经出名了。



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

罗伯特·爱德华兹教授(左)抱着路易斯, 她的妈妈和帕垂克·斯德普投在看着她。

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 fertilisation 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."

九个月前, 路易斯的妈妈莱斯利接受了一项由已故医生帕垂克·斯德普投和罗伯特·爱德华兹以及简·帕迪所做的实验性医疗程序。 这项医疗程序也就是后来广为人知的试管内受精程序, 简称IVF。
布朗女士在成长的过程中一直和这些科学家们保持着联系。

“虽然这听上去有些奇怪, 但他们就像是我的爷爷一样......他们跟爸爸妈妈比起来有点老,”布朗女士在2008年的出生30周年纪念日上跟澳大利亚广播电台讲到, “我们以前常常送生日贺卡给他们, 他们也会送生日贺卡给我们。 而且只要我们有见面的机会那一定会见上一面。 ”

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.

今天, 数以百万计的婴儿通过IVF和其他的先进生育技术降生到这个世界上。
“只要想到我是他们中的第一个......我就会觉得‘噢’,”布朗女士说。



Louise Brown turns 40 today. (Getty Image: Joe Giddens PA Images)

路易斯·布朗40岁了。

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."

悉尼大学生物伦理学家艾因斯利·纽森认为, 辅助生殖技术具有令人难以置信的力量。 “它在问世的40年时间里给很多人带来了欢乐, 也让很多人梦想成真。”纽森医生说, “这次周年纪念日对我们来说是一个机会, 它让人思考我们现在已经走到了何处, 未来将会去往何方。”

The early days: a time of firsts and fights

早期阶段:首创与斗争的年代

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'd 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."

在布朗女士诞生之际, 已故的卡尔·伍德带领的另外一支科学家团队也在世界彼岸的墨尔本从事着IVF的先驱事业。
和英国团队一样, 为了取得一次成功的怀孕他们也已经花费了十年的时间, 位于莫纳什大学的该团队当时的队员艾伦·楚恩森提到。 他表示:“科学界虽然有一些乐观主义精神, 但也有很多其他科学家对此冷嘲热讽。 他们认为这不可能发生, 也会成为一个问题。 ”



Carl Wood and John Leeton in the early days of IVF. (Supplied: Alan Trounson.)

在IVF早期阶段的卡尔·伍德和约翰·里坦。

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.

在布朗女生降生后不久, 澳大利亚的第一个IVF宝宝坎迪斯·瑞德于1980年6月23日出生。 布朗女士和瑞德女生都是利用自然排卵期出生的, 这种方法具有很大的不可预测性。但楚恩森医生和他的同事们想出了另外的方法, 他们开始试验促生殖药物, 试图控制排卵周期。
“试验成功了。 突然间,任何事都有了可能。” 楚恩森医生说。

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.

伍德教授的团队也领先研发了其他技术——如把精子注射进卵子来解决男性不育问题;使用捐献卵子完成了世界首例捐卵怀孕;还有把胚胎冷冻起来, 并进一步使用冷冻胚胎完成了世界首例冷冻胚胎怀孕。



IVF pioneer Alan Trounson in the early 1980s. (Supplied: Alan Trounson)

八十年代早期的IVF先驱艾伦·楚恩森。



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

九十年代到现在:微小之事造就巨大商机

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.

尽管生殖技术曾经只是一项实验, 如今却已经成了标准的医学治疗手段, 改变了异性恋与同性恋夫妇以及单身女性的生活。
2015年在澳大利亚接受IVF治疗的女性平均年龄为35.8岁。 平均大约每23个澳大利亚儿童就有一个是试管宝宝, 其中一半以上是使用冷冻胚胎出生的。



Around 1 in 23 births in Australia are created using assisted reproductive technologies. (News Online Sydney)

在澳大利亚每23个婴儿中就有一个是用辅助生殖技术创造的。

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.

然而生殖技术仍然继续让人们陷于伦理与法律的两难之中。
辅助生殖技术(ART)是一种“对于那些如不然就无法建立家庭的人们来说非常棒的机制,”纽森医生说:“与此同时, 我认为业界很多辅助生殖技术发展的方式是有问题的。”
估计全球范围的不孕不育行业年收益可达40亿澳元。

然而随着这个行业不断增长的商业势头, 人们对个别诊所收取的费用与成功率产生了质疑。使用添加技术, 如用“辅助孵化”化解胚胎外膜, 增加植入的机会和活产比率的做法也引起了长期争论。
“经常会出现技术在得到证据证明确实有效之前就被引入实际操作的例子,”纽森博士说道。
从不孕不育研究转到哈德荪研究所钻研基细胞科学的楚恩森教授也对这种技术的发展表达了担忧。 他说:“我并不支持这种高科技和他们所搞的添加技术。”

Genetic diagnosis to 'three person IVF'

对“三人IVF”技术的基因诊断



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.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 fertilised 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.

2016年, 美国的研究者宣布使用了“三人IVF”技术的婴儿降生, 这在预防一种叫做“线粒体疾病”的罕见基因病上又前进了一步。 这项技术包括用有着健康细胞核的捐献卵子细胞核代替患病女性的细胞核。 新生成的卵子含有捐赠者的健康细胞核, 在受精之后会植入患病女性的体内。
为了绕过美国对胚胎试验的法律规定, 他们在墨西哥实施了该项医疗程序。



Dr John Zhang, who helped pioneer three person IVF. (Supplied: New Hope Fertility Center)

约翰·张博士, 他在三人IVF技术中对先驱技术做出了贡献。

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.

今天, 英国等国都已经允许了该医疗程序的实施。 这项技术虽然在澳大利亚仍然是非法的, 但参议院最近给予了三人IVF技术谨慎的支持, 并推荐调查对关于胚胎研究法律进行修改的可行性。

"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.

“这项法律是在大约15年前通过的。 那时还没有遇见这种技术的产生,”纽森博士解释道,但她也认为存在有很多需要小心行事的理由。
“如果你想做一件事, 而这件事很有可能最后会导致一个人降生到世上, 那么你需要知道该完成的所有事都要在有充分证据支持的情况下完成,” 纽森医生说。 不过, 她补充到, 是时候研究一种既能保持灵活性, 又能让人放心的监管技术的新办法了。
“我认为到了现在这个时候, 我们需要反思应该如何监管这些技术, 使我们在适合创新的时候能够大胆去做,”她说。

The future: embryos from skin cells?

未来:用皮肤细胞创造胚胎?

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.

在过去的40年里科学与伦理的界限受到了冲击。 但如果一种叫做试管内配子的技术——简称IVG——成为现实的话, 那么今后的40年的变革甚至会来得更猛烈。 IVG技术里面包含了IVF的技术, 但在基细胞科学上更加先进。
2012年, 日本科学家山中伸猕由于发现了重新编辑细胞的可能, 而与人分享了诺贝尔奖。这意味着皮肤细胞或血细胞等细胞有可能被转化成卵子和精子细胞。
“虽然他们与胚胎基细胞并不完全相同, 但是非常、非常接近,”楚恩森教授解释道。



Fibroblasts (skin cells) could be reprogrammed into other types of cells in the future. (Getty Images: Science Photo Library)

成纤维细胞(皮肤细胞)在将来可能会被重新编辑成其他种类的细胞。

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.

四年后, 日本科学家林克彦用从雌性老鼠的皮肤细胞提取的所谓诱导干细胞(iPSC)繁殖出一窝健康的小鼠。
克彦医生无法用人类胚胎做这个实验, 但预计十年内这项技术可能会被用来制造人类卵细胞, 尽管他对卵子的质量感到担忧。
楚恩森教授也有着谨慎的乐观情绪。 “技术还达不到那一步。 但是, 我们正在前进的路途之中, 终有一天会达到目标,” 他说。

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.

然而, 尽管制造精子细胞可能会成为现实, 他预计制造卵子细胞可能会难得多, 需要用临近组织的其他细胞来重新编辑皮肤细胞。 “我猜它们同天然的卵子和胚胎相比活力会更低,所以你可能必须制造更多才能达到同样的结果,” 楚恩森教授说道。

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.

纽森医生早在十几年前就研究过IVG技术可能产生的影响。 “这项技术可能会对本身无法生成配偶子(卵细胞和精子细胞)的人有着十分强大的影响,” 她说:“比如那些过早经历更年期的女人。 ” “同样, 出于安全考虑, 它也可能成为同性夫妇可能感兴趣使用的东西。”
由于这种配偶子是用本人的细胞生成的, 这可能会让人们不再需要卵子捐赠或者使用促排药物刺激卵巢。
“我们知道人们很看重基因上的亲缘关系, 但我们看重它的原因会不会是习惯使然呢?”纽森医生说。



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.

2010年, 爱德华兹教授因其在IVF方面的成就被授予了诺贝尔奖。 他在2013年去世。 斯德普投教授没有等到诺贝尔奖, 于1988年去世, 但是他得到了诺贝尔奖委员会的认可。 曾经与斯德普投和爱德华教授并肩工作, 管理实验室和病人的护士帕迪女士于1985年去世, 享年39岁。



Jean Purdy was an IVF pioneer. (Supplied: Bourn Hall)

简·帕迪是IVF的一名先驱者。

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 well-organised 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 recognised as an IVF pioneer. Louise Joy Brown — who now has two children of her own — turns 40 today.

帕迪女士与斯德普投教育和爱德华兹教授一同撰写了26篇论文, 还共同建立了伯恩·海尔不孕不育诊所。
“我们是一个三人团队......她是患者, 永不气馁的帮助者。 没有她的帮助我们的所有工作都不可能实现,”爱德华兹在自传中写到。
尽管帕迪女士发展起来的的医疗程序仍然是今天IVF治疗的一部分, 她的角色却在IVF的故事里以及诺贝尔奖委员会的心中基本被淡忘了。

楚恩森教授在几次场合中见过帕迪女士。 他记得她是一位致力于工作的“害羞并且温柔的人”, 他说:“她是一所管理极佳、运作良好实验室的关键。”
帕迪女士是第一个看到细胞分裂成那个后来成长为布朗女士的胚胎的人。 四十年之后, 人们认可了她在IVF技术上的先驱者地位。
路易斯·乔·布朗——已经有了两个自己的孩子——她今天40岁了。