猪肾脏移植人体首次成功,或将突破器官供应难题
In a First, Surgeons Attached a Pig Kidney to a Human, and It Worked
RONI CARYN RABIN
2021年10月21日
Surgeons in New York have successfully attached a kidney grown in a genetically altered pig to a human patient and found that the organ worked normally, a scientific breakthrough that one day may yield a vast new supply of organs for severely ill patients.
纽约外科医生成功将一只在转基因猪体内生长的肾脏移植到了人类病人身上,并发现该器官工作正常。这一科学突破有朝一日可能为重症病人带来大量新的器官供应。
Researchers have long sought to grow organs in pigs that are suitable for transplantation into humans. Technologies like cloning and genetic engineering have brought that vision closer to reality in recent years, but testing these experimental organs in humans has presented daunting ethical questions.
长期以来,研究人员一直试图在猪身上培育适合移植到人体的器官。近年来,克隆和基因工程等技术使这一愿景更接近现实,但在人类身上测试这些实验器官却存在令人生畏的伦理问题。
So surgeons at N.Y.U. Langone Health took an astonishing step: With the family’s consent, they attached the pig’s kidney to a brain-dead patient who was kept alive on a ventilator, and then followed the body’s response while taking measures of the kidney’s function. It is the first operation of its kind.
因此,纽约大学朗格尼医学中心(NYU Langone Health)的外科医生采取了一项惊人的举措:在征得患者家属同意的情况下,他们将猪的肾连接到一名靠呼吸机维持生命的脑死亡患者身上,然后密切关注身体的反应,同时测量肾脏功能。这是第一次有人进行此类手术。
The researchers tracked the results for just 54 hours, and many questions remained to be answered about the long-term consequences of such an operation. The procedure will not be available to patients any time soon, as there are significant medical and regulatory hurdles to overcome.
研究人员仅对结果进行了54个小时的跟踪调查,关于这种手术的长期后果,还有许多问题有待回答。由于有重大的医疗和监管障碍需要克服,该手术短期内不会提供给病人。
Still, experts in the field hailed the surgery as a milestone.
尽管如此,该领域的专家仍将该手术誉为里程碑。
“This is a huge breakthrough,” said Dr. Dorry Segev, a professor of transplant surgery at Johns Hopkins School of Medicine who was not involved in the research. “It’s a big, big deal.”
“这是一个巨大的突破,”没有参与这项研究的约翰斯·霍普金斯医学院(Johns Hopkins School of Medicine)移植外科教授多里·塞格夫(Dorry Segev)博士说。“这是一件非常非常重要的事情。”
A steady supply of organs from pigs — which could eventually include hearts, lungs and livers — would offer a lifeline to the more than 100,000 Americans currently on transplant waiting lists, including the 90,240 who need a kidney. Twelve people on the waiting lists die each day.
来自猪的器官(最终可能包括心、肺、肝等脏器)的稳定供应,将为目前等待移植的10万多美国人提供一条生命线,其中包括90240名需要肾脏的人。每一天,等待名单上都有12个会人死去。
An even larger number of Americans with kidney failure — more than a half million — depend on grueling dialysis treatments to survive. In large part because of the scarcity of human organs, the vast majority of dialysis patients do not qualify for transplants, which are reserved for those most likely to thrive after the procedure.
更多患有肾衰竭的美国人——超过50万——依靠痛苦的透析治疗来生存。在很大程度上,由于人体器官的稀缺性,绝大多数透析患者不具备移植的资格,移植只留给最有可能在手术后健康存活的人。
The surgery was first reported by USA Today on Tuesday. The research has not yet been peer-reviewed nor published in a medical journal.
《今日美国》(USA Today)周二率先报道了该手术。这项研究还没有经过同行评审,也没有在医学杂志上发表。
The transplanted kidney was obtained from a pig genetically engineered to grow an organ unlikely to be rejected by the human body. In a close approximation of an actual transplant procedure, the kidney was attached to blood vessels in the patient’s upper leg, outside the abdomen.
移植的肾脏来自一头经过基因工程改造的猪,它能生长出一个不太可能被人体排斥的器官。在与实际移植手术非常接近的情况下,肾脏被连接到患者腹部外侧的大腿血管上。
The organ started functioning normally, making urine and the waste product creatinine “almost immediately,” according to Dr. Robert Montgomery, the director of the N.Y.U. Langone Transplant Institute, who performed the procedure in September.
据9月进行手术的纽约大学兰贡移植研究所(NYU Langone Transplant Institute)主任罗伯特·蒙哥马利(Robert Montgomery)说,该器官开始正常运作,“几乎立刻”就开始制造尿液和肌酐废物。
Although the kidney was not implanted in the body, problems with so-called xenotransplants — from animals like primates and pigs — usually occur at the interface of the blood supply and the organ, where human blood flows through pig vessels, experts said.
专家说,尽管肾脏没有被植入体内,但在所谓的异种移植(从灵长类动物和猪等动物身上移植)当中,问题通常发生在血液供应和器官的接口处,也就是人类血液流经猪血管的地方。
The fact that the organ functioned outside the body is a strong indication that it will work in the body, Dr. Montgomery said.
蒙哥马利说,器官在体外发挥作用的事实,有力地表明它在体内也会发挥作用。
“It was better than I think we even expected,” he said. “It just looked like any transplant I’ve ever done from a living donor. A lot of kidneys from deceased people don’t work right away, and take days or weeks to start. This worked immediately.”
“这比我们预期的还要好,”他说。“它看起来就像我做过的任何活体捐赠者的移植手术。很多来自死者的肾脏无法立即工作,需要几天或几周的时间才能开始工作。而这次的移植立即就起作用了。”
Last year, 39,717 residents of the United States received an organ transplant, the majority of them — 23,401 — receiving kidneys, according to the United Network for Organ Sharing, a nonprofit that coordinates the nation’s organ procurement efforts.
据协调美国器官获取工作的非营利组织器官共享联合网络(United Network for Organ Sharing)称,去年,美国有39717名居民接受了器官移植,其中大多数(23401人)是接受肾脏移植。
Genetically engineered pigs “could potentially be a sustainable, renewable source of organs — the solar and wind of organ availability,” Dr. Montgomery said.
基因工程猪“有可能成为一种可持续的、可再生的器官来源——相当于器官供应的太阳能和风能”,蒙哥马利说。
The prospect of raising pigs to harvest their organs for humans is bound to raise questions about animal welfare and exploitation, though an estimated 100 million pigs already are killed in the United States each year for food.
尽管据估计,美国每年有1亿头猪被宰杀作为食物,但为了获取人体器官而养猪的前景,必然会引发有关动物福利和剥削的问题。
“Pigs aren’t spare parts and should never be used as such just because humans are too self-centered to donate their bodies to patients desperate for organ transplants,” said a statement from the organization People for the Ethical Treatment of Animals, or PETA.
善待动物组织(PETA)在声明中说:“猪不是多余的器官,也不应该被用作多余的器官,只因为人类太自我中心,不愿意把自己的身体捐赠给迫切需要器官移植的病人。”
Among transplantation experts, reactions ranged from cautiously optimistic to ebullient, though all acknowledged the procedure represented a sea change.
移植专家们反应不一,从谨慎乐观到热情高涨都有,不过所有人都承认这是一个巨大的变化。
While some surgeons speculated that it could be just months before genetically engineered pigs’ kidneys are transplanted into living human beings, others said there was still much work to be done.
虽然一些外科医生推测,将基因工程猪的肾脏移植到活人身上可能只需要几个月的时间,但也有人说仍有很多工作要做。
“This is really cutting-edge translational surgery and transplantation that is on the brink of being able to do it in living human beings,” said Dr. Amy Friedman, a former transplant surgeon and chief medical officer of LiveOnNY, the organ procurement organization in the greater New York area.
“这是真正尖端的转化手术和移植,即将在活人身上实现,”前移植外科医生、大纽约地区器官采购组织LiveOnNY的首席医疗官艾米·弗里德曼(Amy Friedman)说。
The group was involved in the selection and identification of the brain-dead patient receiving the experimental procedure. The patient was a registered organ donor, and because the organs were not suitable for transplantation, the patient’s family agreed to permit research to test the experimental transplant procedure.
该组织参与了接受实验手术的脑死亡患者的选择和识别工作。这位病人是注册过的器官捐赠者,由于器官不适合移植,病人的家人同意在其身上研究测试实验性移植程序。
Dr. Friedman said she envisioned using hearts, livers and other organs grown in pigs, as well. “It’s truly mind-boggling to think of how many transplants we might be able to offer,” she said, adding, “You’d have to breed the pigs, of course.”
弗里德曼说,她还设想使用猪的心脏、肝脏和其他器官。“想想我们能提供多少移植手术,这真的令人难以置信,”她还说。“当然,我们需要培育这些猪。”
Other experts were more reserved, saying they wanted to see whether the results were reproducible and to review data collected by N.Y.U. Langone.
还有一些专家则比较谨慎,他们说希望看看这些结果是否具有可重复性,并审阅纽约大学兰贡学院收集的数据。
“There’s no question this is a tour de force, in that it’s hard to do and you have to jump through a lot of hoops,” said Dr. Jay A. Fishman, associate director of the transplantation center at Massachusetts General Hospital.
“毫无疑问,这是一项壮举,因为这很难做到,必须克服很多困难,”马萨诸塞州总医院(Massachusetts General Hospital)移植中心副主任杰伊·A·菲什曼(Jay A. Fishman)说。
“Whether this particular study advances the field will depend on what data they collected and whether they share it, or whether it is a step just to show they can do it,” Dr. Fishman said. He urged humility “about what we know.”
“这项研究是否会推动该领域的发展,将取决于他们收集了什么数据,以及他们是否分享这些数据,或者这只是表明他们可以做到这件事中的一个步骤,”菲什曼说。他呼吁以谦逊的态度对待“我们的所知”。
Many hurdles remain before genetically engineered pigs’ organs can be used in living human beings, said Dr. David Klassen, chief medical officer of the United Network for Organ Sharing.
器官共享联合网络的首席医疗官戴维·克拉森(David Klassen)博士表示,在将转基因猪的器官用于活人身上之前,还有许多障碍。
While he called the surgery “a watershed moment,” he warned that long-term rejection of organs occurs even when the donor kidney is well-matched, and “even when you’re not trying to cross species barriers.”
虽然他把这次手术称为“一个分水岭时刻”,但他警告说,即使捐赠者的肾脏匹配度很高,而且“即使你没有试图跨越物种障碍”,也会发生器官的长期排斥。
The kidney has functions in addition to clearing blood of toxins. And there are concerns about pig viruses infecting recipients, Dr. Klassen said: “It’s a complicated field, and to imagine that we know all of the things that are going to happen and all the problems that will arise is naïve.”
除了清除血液中的毒素外,肾脏还有其他功能。还有人担心猪病毒会感染接受者,克拉森说:“这是一个复杂的领域,认为我们可以知道所有将会发生的事情和所有将会出现的问题,那就太天真了。”
The combination of two new technologies — gene editing and cloning — has yielded genetically altered pig organs. Pig hearts and kidneys have been transplanted successfully into monkeys and baboons, but safety concerns precluded their use in humans.
两项新技术——基因编辑和克隆——的结合产生了基因改变的猪器官。猪的心脏和肾脏已被成功地移植到猴子和狒狒体内,但出于安全考虑,它们不能用于人类。
“The field up to now has been stuck in the preclinical primate stage, because going from primate to living human is perceived as a big jump,” Dr. Montgomery said.
“到目前为止,这一领域一直停留在灵长类动物临床前阶段,因为从灵长类动物到活人被认为是一个大飞跃,”蒙哥马利说。
The kidney used in the new procedure was obtained by knocking out a pig gene that encodes a sugar molecule that elicits an aggressive human rejection response. The pig was genetically engineered by Revivicor and approved by the Food and Drug Administration for use as a source for human therapeutics.
在新手术中使用的肾脏是通过敲除猪的一种基因获得的,这种基因编码一种糖分子,会引发强烈的人类排斥反应。这头猪由Revivicor公司进行基因工程改造,并获得美国食品和药物管理局(Food and Drug Administration)的批准,可作为人类治疗的来源。