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Seeking Cures, Patients Enlist Mice Stand-Ins

BALTIMORE — Megan Sykes, a medical researcher, has a mouse with a human immune system — her own. She calls it “Mini-Me.”

巴尔的摩——医学研究人员梅根·塞克斯(Megan Sykes)有一只有着人类免疫系统的老鼠,其实就是她本人的免疫系统。她把它叫做“迷你的我”。

There are also mice containing a part of 9-year-old Michael Feeney — a cancerous tumor extracted from his lungs. Researchers have tested various drugs on the mice, hoping to find the treatment that would work best for Michael.

另一些老鼠则带有一名九岁男孩迈克尔·菲尼(Michael Feeney)身体的一部分——一个从他肺里摘除的癌变肿瘤。研究人员在这些老鼠身上试验了各种药品,以希望能找出治疗迈克尔的最好方法。


In what could be the ultimate in personalized medicine, animals bearing your disease, or part of your anatomy, can serve as your personal guinea pig, so to speak. Some researchers call them avatars, like the virtual characters in movies and online games.


“The mice allow you the opportunity to test drugs to find out which ones will be efficacious without exposing the patient to toxicity,” said Colin Collins, a professor at the University of British Columbia.

“这些老鼠给你提供了测试药物的机会,这样就避免了让病人承担中毒的风险,而且还能找出哪些药效果好。”不列颠哥伦比亚大学(University of British Columbia)教授科林·科林斯(Colin Collins)说。

Experiments on mice have been done for decades, including implanting people’s tumors into the animals. But the techniques have improved in the last few years and interest is growing. The National Institutes of Health held a workshop on personalized animal models earlier this month. And while the models are mainly being used for research, companies are beginning to commercialize them for use in drug development and medical treatment as well.

用老鼠来做试验已经有数十年的历史,包括移植人类肿瘤到动物体内。但是在过去的几年里,医学技术取得了巨大的进步,同时对动物试验的兴趣也在增长。本月初,美国国家卫生研究院(National Institutes of Health)举办了一个关于个性化动物模型的研讨会。虽然所讨论的动物模型还是主要用于实验目的,但是一些公司已经开始将其商业化,用于药品开发和医务治疗。

Experts caution that it has not been proved that the use of avatars will prolong the lives of cancer patients. And it costs tens of thousands of dollars, which insurers will not cover, to create and test a colony of the animals.


“It’s an act of faith to say this is a superior way of proceeding,” said Dr. Edward Sausville, a professor of medicine at the University of Maryland.

“说这是最好的治疗方案,那简直是对信仰的考验。”马里兰大学(University of Maryland)医学教授爱德华·索斯维尔(Edward Sausville)博士说。

But some cancer patients, wanting to try everything possible, are turning to the mice anyway.


“This just seems right to us,” said Jill Feeney, the mother of Michael, who has been fighting a type of bone cancer called Ewing’s sarcoma since 2009, when he was 6. “It’s actually his tumor growing somewhere, and we’re treating it the way he would be treated.”

“这对我们来说,似乎是正确的选择。”迈克尔的妈妈吉尔·菲尼(Jill Feeney)说。从2009年开始,迈克尔一直在和一种叫做尤文氏肉瘤(Ewing’s sarcoma)的骨癌进行抗争,那时他才6岁。“那就是他的肿瘤,只是长在了别的地方,采用的治疗方法就是将来用在他身上的方法。”

When Michael had surgery in February to remove a tumor that had spread to a lung, a courier was waiting outside the operating room in New York to whisk the tumor to a laboratory here run by a company called Champions Oncology.

2月份,迈克尔做了手术,摘除了一个已经扩散到肺部的癌症肿瘤。当时,一个快递员就等在纽约的手术室外,等着把肿瘤送到这里一家名叫冠军肿瘤学的公司(Champions Oncology)的实验室去。

Four hours later, technicians cut the tumor into five pieces and placed each piece under the skin of an anesthetized mouse. Two months later, after the tumors had grown, they were removed, cut into pieces and each piece implanted into another mouse. A month later there were enough mice models to begin testing.


The Feeneys, who live in Ridgewood, N.J., paid $25,500 for the creation of the avatars and the testing of four different drugs or drug combinations.


The results came back in July. A combination of four drugs — gemcitabine, docetaxel, Avastin and Afinitor — was “astonishingly active” in shrinking the tumor in the mice, said Michael’s oncologist, Dr. Leonard H. Wexler of the Memorial Sloan-Kettering Cancer Center. Dr. Wexler said that the combination was not something oncologists would typically choose.

7月,结果出来了。一种四种药物的组合——吉西他滨、多西他奇、阿伐麦布和依维莫司——在促使老鼠肿瘤萎缩中表现出“惊人疗效”,负责迈克尔的肿瘤专家,斯隆-凯特琳癌病中心(Memorial Sloan-Kettering Cancer Center)的莱纳德·H·韦克斯勒(Leonard H. Wexler)博士说。他还说,肿瘤医生一般不会选择使用这种药物组合。

Michael has not tried the combination yet because he is participating in a clinical trial of an experimental drug. But if that drug does not work, his mother said, “we have the home run in the back pocket.”


Cancer is not the only area where the animal models may be useful.


Dr. Sykes, a professor at Columbia, led the team there and at Massachusetts General Hospital that replicated an individual’s immune system in mice using a bone marrow sample from the person’s hip. The immediate goal is to study how Type 1 diabetes, an autoimmune disease, develops. But in the future, she said, such “personalized immune mice” might produce immune cells that can be transplanted into the patient to help fight disease.

哥伦比亚大学(Columbia University)教授赛克斯博士领导该大学和马萨诸塞州综合医院(Massachusetts General Hospital)的研究队伍,他们通过从人体髋骨提取骨髓样本,在老鼠的身上复制了这个人的免疫系统。这项工作眼前的目标,是研究I型糖尿病(一种免疫系统疾病)的发病和发展。但她说,未来这种“用于个性化治疗的免疫小鼠”可能会产生免疫细胞,这些细胞可以植入患者体内,帮助他们抵抗疾病。

At Washington University in St. Louis, Dr. Jeffrey Gordon has transplanted the collection of bacteria in a person’s intestines into mice. The “humanized” mice might be used to study, for instance, how a change in diet could influence the person’s health.

圣路易斯华盛顿大学(Washington University)的杰弗里·戈登(Jeffrey Gordon)博士将人体的肠道菌群移植到了老鼠体内。“人类化”的老鼠可能被用于研究工作,比如,研究饮食改变对人体健康的影响。

In cancer, drugs that work in mice do not always work in people. But some studies suggest that tumors freshly implanted from patients more closely resemble human disease than those created by the common technique of implanting tumor cells that have been cultured in a laboratory dish.


“It’s the closest we can get to the real deal,” said Alana Welm, a breast cancer researcher at the University of Utah.

犹他大学(University of Utah)乳腺癌研究人员阿拉纳·韦尔曼(Alana Welm)说,“这是我们最接近实际情况的方法。”

Still, the stand-ins are not perfect surrogates. A tumor implanted under the skin of a mouse might not behave the same as it did in the human breast, lung or other organ from which it was extracted. Unlike people, the mice are bred to have a deficient immune system, so they will not reject the human tumor.


There are also practical problems. Sometimes, patient tumors do not grow in the mice at all, and it takes at least four months to create enough mice to test a reasonable number of drugs. Dr. Harvey Pass, a thoracic surgeon at New York University, said four of the eight patients he referred to Champions died before any results from the mice came back.

还有一些实际问题。有时候,患者的肿瘤根本不能在老鼠体内生长,至少需要四个月的时间才能培养出足够多的老鼠来测试必要数量的药物。纽约大学(New York University)胸外科医师哈维·帕斯(Harvey Pass)博士表示,他推荐到冠军肿瘤学公司的八名患者中有四名在老鼠试验结果还没出来前就去世了。

Dr. Ronnie Morris, the president of Champions, said the company has had about 160 patients so far and has tested drugs on mice for 60 of them. The other patients either died too soon, or the tumor did not grow in the mice, or the patients are too new to have reached the drug testing stage.

冠军肿瘤学公司总裁龙尼·莫里斯(Ronnie Morris)博士表示,该公司到目前为止共接收了160名患者,他们利用老鼠为其中60名患者进行了药物测试。其他患者或是过早去世了,或是他们的肿瘤未能在老鼠体内生长,或者患者是新近接收的,还没有到药物测试的阶段。

Champions, started by two prominent oncologists from Johns Hopkins, published a paper last year reporting on 14 patients. The mouse testing found a drug or drug combination that could shrink tumors for 12 of them.

冠军肿瘤学公司是由约翰·霍普金斯大学(Johns Hopkins University)两位著名的肿瘤学家开创的。该公司去年发表了有关14名患者治疗情况的论文。老鼠试验的结果找到了一种药物或者药物组合,能够使其中12名患者的肿瘤缩小。

Tumor shrinkage does not always mean longer life, however, and skeptics say randomized trials are needed to prove patients using avatars will fare better than they would have otherwise. Better evidence is also likely to be needed before insurers would pay for the use of avatars.


Some experts say that testing a tumor for genetic mutations is a far more practical way to figure out which drug may work best. But that technique, at least for now, does not always yield a useful result. Nir Toib, an Israeli filmmaker with lung cancer, said treatments suggested by a genetic analysis of his tumor did not work, but that a combination of two drugs suggested by the avatar testing did.

一些专家表示,要想搞清楚哪种药物作用最好,更为实用的办法就是检测肿瘤的基因突变。但至少现在,这种技术并不一定能带来有效的结果。身患肺癌的以色列电影制作人尼尔·托伊布(Nir Toib)说,他根据肿瘤基因分析所做的治疗并不起作用,但替身试验得出的结论——同时使用两种药物——对他确实有效。

“I had 10 tumors on my right kidney,” said Mr. Toib. “All of them disappeared.”


While Mr. Toib joked that he had himself “cloned” in the mice, neither he nor most other patients feel any personal attachment to their mice.


“You just look at it as a tool for saving yourself,” said a 60-year-old New Jersey man with lung cancer who asked that his name not be used to protect his privacy. “From my perspective, the more that die, the better for me.”

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