基因抗癌:承诺与心碎
基因抗癌:承诺与心碎
Beth McDaniel’s oncologist, a bear of a man, hugged her and twirled her around.
贝丝·麦克丹尼尔(Beth McDaniel)的肿瘤医生是一个壮实如熊的男人,他激动地抱着她原地转了一圈。
“Holy cow, Beth!” Dr. John J. Gohmann exclaimed.
“太棒了,贝丝!”约翰·J.戈曼博士(John J. Gohmann)惊叹道。
For the first time since a rare cancer appeared eight years before, her lymph nodes had shrunk to a normal size, her skin was no longer bright red and inflamed, and the itchiness that plagued her had subsided.
自从八年前患上一种罕见的癌症以来,这是麦克丹尼尔女士的淋巴结第一次缩小到正常大小,她的皮肤不再红肿,困扰她的皮肤发痒也消退了。
Mrs. McDaniel, the 69-year-old wife of a retired corporate executive, had gambled on the ultimate in personalized medicine, an approach known as whole genome sequencing, and it seemed to be paying off.
麦克丹尼尔女士当时69岁,她的丈夫退休前是一位企业高管,她把自己抗癌的希望押注在最前沿的个性化医学上,那是一种称为全基因组测序的方法,她似乎赌赢了。
Scientists had compared the entire genetic sequences of the tumor cells invading her body with those in her healthy cells, searching for mutated tumor genes that could be thwarted by drugs approved for other cancers or even other diseases. That had led them to give her an expensive drug approved just a month earlier for melanoma patients. It had never been given to anyone with a blood cell cancer like hers. In theory, the drug should have killed her. Instead, it seemed to have halted or even reversed her cancer.
科学家们把她体内的肿瘤细胞和健康细胞的全基因序列相对比,找到突变的肿瘤基因,在已获得批准治疗其他癌症或其他疾病的药物中,寻找能抑制这些基因突变的药物。科学家们由此给她开出了一种昂贵的药物,这个药刚在一个月前获得批准用于黑色素瘤患者的治疗,此前并没有用来治疗她患的这种血细胞癌。从理论上讲,这种药物可能导致她死亡。事实则刚好相反:这个药看来似乎抑制、甚至逆转了她的癌症。
But would it last? And what would it mean if it did not?
但这能持续多久? 如果这种药的疗效不能持续,那么这意味着什么?
In the end, Mrs. McDaniel’s journey to the edge of genetics research turned out to be a decidedly mixed experience. It was hard — much harder than anyone in her family had imagined — to get the sequencing and analysis done. It was breathtaking to see the results, which indicated that her cancer was driven by a strange gene aberration that could be attacked with a new drug. But it was heartbreaking to see how quickly her cancer recovered from the assault, roaring back in a matter of weeks.
最终,麦克丹尼尔见证了遗传学最前沿的研究,走过了一段跌宕起伏的历程。基因测序和分析的难度超过了她的家人的想象。结果是令人惊叹的,测序分析表明一个奇怪的基因异常导致她罹患癌症,而一种新药可以与这个基因突变作战。但令人心碎的是癌症只偃旗息鼓了几周,不久就卷土重来。
Mrs. McDaniel’s story offers a sobering look at the challenges for this kind of quest for a treatment, even for someone like her, who had both the means and the connections to get the intricate geography of her cancer charted. Her husband, Roger McDaniel, was a former chief executive of two companies involved in semiconductor manufacturing, and the family could afford the approximately $49,000 that the search would cost. They had expected to pay much more, but to their astonishment, Mrs. McDaniel’s insurance company covered almost all the drug costs. And the scientists who did the data analysis did not charge.
麦克丹尼尔女士的亲身经历揭示了这种新的治疗方法在实践中面临的挑战,即使像她这样的人也要经历重重困难——她本人既有财力、又有人脉,能够做如此复杂的癌症基因组测序分析。她的丈夫罗杰·麦克丹尼尔(Roger McDaniel)曾在半导体制造行业的两家公司担任首席执行官,她家里负担得起约4.9万美元的基因组测序分析费用。他们一家原本还准备承担更高的医疗费,但令他们惊讶的是,她的保险公司支付了几乎所有的药费。而做测序数据分析的科学家们则没有收费。
From the start, the family knew the odds were against Mrs. McDaniel, but she thought she had little to lose.
从一开始,家人就知道她在这场基因赌博中的胜算并不大,但她认为自己也没什么放不下的东西了。
“You cannot feel bad if this doesn’t work or I die,” she told her son Timothy, a molecular biologist. “I would have died anyway.”
“如果这种方法不起作用,或者我就这么走了,你不要伤心,”她对做分子生物学研究的儿子蒂莫西(Timothy)说:“反正左右都是死啊。”
Scarlet Skin and Infections
猩红色皮肤和皮炎
Beth McDaniel’s cancer began with itching all over her body. Then her skin turned scarlet and started becoming infected.
贝丝·麦克丹尼尔的癌症始于全身发痒。然后她的皮肤变成猩红色,接着开始发炎。
In 2005, after she had spent more than a year going from specialist to specialist, a dermatologist figured it out. Mrs. McDaniel, then 62, had Sezary syndrome, a rare T cell lymphoma, in which white blood cells become cancerous and migrate to the skin. All her doctors could tell her was that the disease was incurable, that there was no standard treatment, and that on average patients at her stage die within a few years.
她花了一年多时间,看了无数专家,终于在2005年,一位皮肤科专家找到了确切的病因:时年62岁的麦克丹尼尔患了Sezary综合征,这是一种罕见的T细胞淋巴瘤,患者的白细胞发生癌变,并转移到皮肤。她的医生们如实告诉她,这种病无法治愈,也没有标准的治疗方法,处在她这个分期的患者,平均存活时限不到几年。
“Of course I was shocked,” Mrs. McDaniel said in an interview last September.
“当然,我很震惊,”麦克丹尼尔女士去年9月在接受记者采访时说。
She wept that day as her husband drove her home. And she asked God to help her cope.
确诊后的那天,丈夫开车带她回家,她哭了一路,祈求上帝帮助自己应对这一切。
Before cancer, she had had a vibrant life, hiking in the mountains, traveling the world, entertaining her wide network of friends. Her disease destroyed all of that. She could not even enjoy her luxuriant garden because sun on her inflamed skin was agony.
患癌症之前,她的生活多姿多彩:游山玩水,周游世界,款待亲朋。一场病毁了这一切。她甚至不能好好欣赏家里修剪得整整齐齐的花园,因为一被阳光晒到,发炎的皮肤就会非常疼痛。
Although there is no standard treatment, for five years chemotherapy held her disease at bay. But in the summer of 2010, she got worse, much worse, with hundreds of tumors popping up under her skin. Some grew as large as kiwi fruits and split open.
虽然没有标准的治疗方法,但化疗还是使她的病情缓解了五年的时间。但在2010年夏天,她的病情急转直下,上百个肿瘤包块从她的皮肤下面窜出来。有些包块甚至能长到猕猴桃那么大,然后破溃。
Her son, Dr. McDaniel, decided he would orchestrate the use of the most advanced techniques of gene sequencing and analysis to take on her cancer. Because of his job — he works for Illumina, a company that does DNA sequencing — Dr. McDaniel had read scientific reports and gone to medical conferences where he heard talks on whole genome sequencing. He noticed that the patients all seemed to have rare cancers.
她的儿子麦克丹尼尔博士决定亲自上阵,使用最先进的技术对她的癌症进行基因测序和分析。当时他在一家专门做DNA测序的公司Illumina公司工作,读过很多相关科学报告,参加过很多医学学术会议,在这些会议上他听过各种全基因组测序的研究报告。他注意到,这些做基因测序的病例似乎都患有罕见的癌症。
“Every time I heard one of those stories, I thought, ‘That’s my mom,’ ” he said.
“每当我听到这些病例报告,我就会想,‘我妈妈就是那个病例’,”他说。
For now, there are not many drugs that can target specific gene mutations in cancer cells.
到目前为止,针对癌细胞中特定基因突变的靶向治疗药物还不是很多。
But the hope is that when more is known and more drugs are developed, doctors will treat cancer by blocking several major genes at once. With several escape routes barred, the cancer will not be able to break free of the drugs stopping its growth.
但人们希望,随着基因研究的发展和更多新药物的研发,将来医生可以通过同时抑制几个关键基因来治疗癌症。几条逃生路线被同时阻断,这样,癌症将无法突出重围,摆脱药物的重重封锁。
Full-Time Help From a Son
儿子的全时专业服务
In theory, it seemed straightforward for Dr. McDaniel to help his mother. The technology for getting and analyzing DNA sequences has advanced greatly, and the cost has plummeted. In fact, Dr. McDaniel said, the price of sequencing has dropped so fast that if the work were done today, it would cost just $26,200 instead of the $46,280 it cost last year.
从理论上来说,麦克丹尼尔博士似乎能轻而易举地为他妈妈做基因测序。获取和分析DNA序列的技术都取得了很大进展,测序费用直线下降。他介绍说,测序费用降得非常快,如果今天做测序,那么就只要花26200美元,而在去年,还需要花46280美元。
The first obstacle was just getting a sample of Mrs. McDaniel’s cancer cells. One doctor told her the odds of success were so slim that she would be better off spending her money on a vacation. Another seemed interested but did not follow through. A third did two biopsies but was unable to get usable DNA.
第一个难关是活检取得麦克丹尼尔女士的癌细胞样本。一位医生告诉她,这种方法成功的可能性非常渺茫,她还不如拿着这笔钱度个假。另一位医生似乎有兴趣,但并没有接手。第三位医生给她做了两次活检,但未能取得可用于测序的DNA。
Finally, Dr. McDaniel and his wife, Gia, decided he would make helping his mother a full-time job. He took a leave of absence from Illumina, and he, Gia and their three young children moved from San Diego to Lexington, Ky.
最后,麦克丹尼尔博士和妻子吉娅(Gia)做出了一个决定:他应当把帮助自己的妈妈当作全职工作来完成。他向公司告假,然后与妻子带着他们的三个孩子,从圣地亚哥举家搬迁到肯塔基州的列克星敦市。
“I have not been a particularly humble person,” Beth McDaniel said. “That humbled me.”
“一直以来,我不是一个特别谦卑的人,”贝丝·麦克丹尼尔说:“这个举动使我变得谦卑。”
Dr. McDaniel’s parents had two homes in the Lexington area. One, on a horse farm, was vacant, and he appropriated a bedroom on the second floor for his office. He treated his work like a regular job, driving to the office each day from another house where he and his family were living. He dressed in his normal work clothes, slacks and a collared shirt. Meanwhile, his mother’s cancer was erupting.
在列克星敦地区,麦克丹尼尔博士的父母拥有两所房子。其中一所房子建在马场边,当时是闲置的,他将二楼的一间卧室改为办公室。他像对待正式工作那样,每天从家里开车去办公室。他在办公室穿着正式的工作服、长裤和衬衫。此时,母亲的癌症恶化了。
“She was covered in tumors, almost like cobblestones,” said Dr. Fernando R. de Castro, her dermatologist. “They felt like marbles and pebbles all over her skin.” Large ones on her arms and legs had burst open. “We started talking about hospice.”
“她浑身就像石子路一样,上面长满了肿块,”她的皮肤科医生费尔南多·R.德卡斯特罗博士(Dr. Fernando R. de Castro)说:“这些肿块摸上去,就跟大理石和鹅卵石一样。”她的胳膊和腿上有几个大的包块都溃裂了。“我们开始谈到临终关怀。”
Mrs. McDaniel said she was not a vain person, but with red lumps all over her face, she was embarrassed to go out. She slept on a cooling pad and carried one with her to relieve the constant itching.
麦克丹尼尔女士说自己不是一个虚荣的人,但脸上长满了红色肿块,这让她不好意思出门。 她睡在冰垫上,还要随身带一个冰垫,以缓解持续不断的皮肤瘙痒。
Every evening around 5:30 when the itching became most unbearable, she would lay her head in her husband’s lap as they watched TV in their great room and he would gently tickle her back for hours on end — trying to ease her discomfort.
每天晚上五点半左右,在皮肤瘙痒最难以忍受的时候,她就把头枕在丈夫的腿上,他们一起在大房间里看电视,长达几个小时的时间,他轻轻地给她挠背,想要减轻她的痛苦。
The disease continued a relentless course until finally, accepting what seemed the inevitable, Mrs. McDaniel gave away her clothes, planned her funeral and wrote notes to a few people she thought she had offended in her life, asking them to forgive her.
疾病持续恶化,最终,她接受了似乎是不可避免的命运,于是开始把自己的衣服送人,安排后事,她给一些自认为得罪过的人留下遗言,请求他们原谅自己。
“She believed, we all believed, she would die before we got the sequencing done,” Dr. McDaniel said.
“她认为,我们所有人也都认为,她已经等不到完成基因测序的那一天了,”麦克丹尼尔博士说。
Then, in January 2011, Dr. de Castro got a tissue sample from a tumor and, for comparison with normal cells, her saliva. He had removed a plug of tissue the size of a pencil eraser from one of the hundreds of tumors on Mrs. McDaniel’s skin, frozen it in liquid nitrogen and shipped it overnight to the Mayo Clinic in Scottsdale, Ariz. By April, scientists at Illumina and TGen, a nonprofit research institute, had completed the genetic sequencing of the samples.
结果,在2011年1月,德卡斯特罗终于取到了活检的肿瘤组织样本,为了与正常细胞相比,他还取了她的唾液样本。麦克丹尼尔女士皮肤上遍布数以百计的肿瘤,他从其中一个肿块上取得了铅笔橡皮擦大小的活体组织,样本冷冻在液氮中,连夜递送到位于亚利桑那州斯科茨代尔的梅奥医学中心(Mayo Clinic)。到了2011年4月,Illumina公司和TGen研究院(一个非营利性研究机构)的科学家们完成了样本的基因测序。
Next came the hard part — the analysis. With time short, Dr. McDaniel worked on it himself and recruited two small biotechnology companies and TGen to help.
接下来是最困难的部分——序列分析。时间紧迫,麦克丹尼尔博士亲自上阵,并取得了TGen研究院和两个生物技术小公司的支持。
Three Billion Symbols in a Cell
一个细胞中有30亿个核苷酸符号
John Carpten, an oncologist at TGen, and David Craig are accustomed to working with gene sequence data, but it is hard even for them to get used to the scale of such a project.
约翰·卡普顿(John Carpten)是TGen研究院的肿瘤学家,他和大卫·克雷格(David Craig)都是基因序列数据分析的熟手,但即使他们也很难适应这个项目的庞大数据量。
The hard drive containing Mrs. McDaniel’s genetic data arrived in the mail — it had too much data to send electronically. It took a full day just to pull this terabyte of information off the drive. Dr. Carpten explained that there were three billion symbols, made from four letters — A, T, G and C — in just one cell’s DNA. If those letters were printed on paper, they would fill a medium-sized elementary school’s library.
麦克丹尼尔女士的基因数据是存储在硬盘驱动器,通过邮寄递送的(因为数据量太大,所以无法通过互联网传送)。光是从硬盘驱动器把这万亿字节的数据信息读取出来就花了一整天的时间。卡普顿解释说,仅仅一个细胞中的DNA就有30亿个核苷酸符号,代码是A、T、G和C四个字母。如果把这些字母打印到纸上,那么一个细胞中的DNA数据量就能填满一个中等规模小学的图书馆。
But there are unavoidable errors in sequencing, so to be sure the data is correct, researchers repeat the sequencing 30 times — 30 libraries’ worth. They do this for the normal cells, too — another 30 libraries’ worth. This kind of data, though, does not come in neat genetic words and sentences. Instead, Dr. Craig said, “It looks like it’s been through a shredder.”
测序时不可避免会发生差错,为了确保数据准确无误,研究人员对每个样本都要做30次的重复测序,也就是30个图书馆的数据量。做比较的正常细胞也这么测序——又多了30个图书馆的数据量。非但如此,这种数据并不是整齐的基因词组和句子的形式。恰恰相反,克雷格博士说,“测序数据是碎片段,看起来像是被碎纸机裁切过一遍似的。”
“It is like putting together a jigsaw puzzle that has a billion pieces,” Dr. Carpten said.
“这就像是拼接有10亿片碎片的拼图,”卡普顿博士说。
Finally, they compared the sequences of normal cells and cancer cells. They found about 18,000 differences, most with no known significance for the disease.
最后,他们把正常细胞和癌细胞的基因序列进行比较,结果发现了约1.8万个差异位点,但其中大多数都没有已知的致病意义。
At last, the work was done, and on May 18, Dr. McDaniel flew to TGen. The researchers noticed an intriguing aberration in Mrs. McDaniel’s cancer genes. But they were uncertain what it meant.
终于,序列分析工作完成了,在5月18日,麦克丹尼尔博士飞赴TGen研究院。 研究人员们在麦克丹尼尔女士的癌症基因中发现了一个可疑的基因变异,但是他们不能确定这个变异意味着什么。
It looked as if two genes had fused to each other in Mrs. McDaniel’s cancer cells. The result was that the cell growth signals in the cancer cells were reversed, like crossed wires. The research team theorized that every time those cancer cells, T cells of her immune system, got a signal to stop growing, they reacted as though they had gotten a signal to grow. And every time they got a signal to grow, they responded by stopping their growth.
看起来麦克丹尼尔女士的癌细胞中,两个基因似乎相互融合,其结果是使得癌细胞中细胞生长的信号传导通路就像接反了的交叉线。研究小组推测,她免疫系统的T细胞癌每次得到了抑制增长的信号,这些癌细胞的反应却是如同得到了刺激增长的信号,结果会继续增长。而每次得到了刺激增长的信号,这些癌细胞的反应就是停止增长。
If they were right, the way to stop her cancer’s growth could be to signal it to grow. And that was what a new melanoma drug — ipilimumab, its trade name Yervoy — was designed to do. It spurred the growth of normal T cells.
如果他们的推测是正确的,那么就应该施加刺激T细胞增长的信号,以抑制她癌症的增长。有一种新药刚好可以用来治疗刺激正常T细胞增长,这种药通用名为易普利姆玛(ipilimumab),商品名是伊匹单抗(Yervoy),是一种治疗黑色素瘤的新药。
But if the researchers were wrong, the drug could kill her.
但是如果研究人员的推测是错误的,那么这种药很可以会断送她的性命。
They spent two hours at a whiteboard on Wednesday, May 18, trying to understand what the fusion really meant. Then Dr. McDaniel took the data home and asked a colleague at Illumina to try to fish out a handful of crucial genetic sequences that were buried among 50 million others. On Sunday night, May 22, Dr. McDaniel had them and began trying to decipher them. By 10 p.m., he had it figured out. The TGen scientists’ findings were real.
在5月18日,星期三,他们站在白板前讨论了两个小时,试图弄清这个基因融合的确切含义。随后,麦克丹尼尔博士带着测序分析的数据赶回家,请Illumina公司的同事从含有5000万个基因序列的数据库中,帮他再找出几个关键的基因序列。 5月22日(星期日)晚上,他得到了这几个基因序列,马上开始破译分析。到了晚上10点,他弄明白了:TGen研究院的科学家们发现的基因融合是确切的。
“The brake pedal had been wired to the accelerator,” Dr. McDaniel said.
“刹车踏板被连到油门上,”麦克丹尼尔博士这样形容这种基因融合。
He worked all night, found a paper by scientists who had deliberately fused those very genes and discovered that, yes, the genetically altered T cells had their growth signals reversed.
他工作了一整夜,查阅到了一篇科研论文,发现科学家曾有意融合了这两个特异的基因,结果发现在基因融合后,确实发生了T细胞增长信号的逆转。
At 5:45 a.m. Dr. McDaniel sent an e-mail to his collaborators.
在早晨5点45分,麦克丹尼尔博士给合作者们发了一封电子邮件。
“I was so tired at that point that, believe it or not, I had forgotten about the drug,” he said.
“我当时实在太疲惫了,不管你信不信,我竟然忘记在邮件中提到这个治疗药物,”他说。
He fell asleep and woke at 11 a.m., rushing back to his computer. The melanoma drug he had forgotten in his exhaustion should hit that target. And that could stop his mother’s cancer from growing. “My jaw was just hanging open,” Dr. McDaniel said. “The implications were so tantalizing that I didn’t dare believe them.”
他睡着了,一觉醒来已经是上午11点钟,他立马赶到电脑前工作。他在疲惫中忘记提到的治疗黑色素瘤的药物,应该能够一举击中这个基因变异位点,由此他母亲的病情发展就能被抑制住。“我当时惊喜得合不拢嘴,”麦克丹尼尔博士说:“这个分析结果的含义是如此激动人心,以至于我都不敢相信。”
A Remarkable Turnaround
病情显著好转
Mrs. McDaniel had her first infusion on July 28, and the result seemed remarkable. Her oncologist, Dr. Gohmann, was overwhelmed. Her son, who had been terrified that he and the doctors might have made a terrible mistake, was overjoyed.
在7月28日,麦克丹尼尔女士打了点滴,第一次用上了这种药,效果似乎很显著。她的肿瘤医生戈曼博士惊叹不已。她的儿子一直担心他和医生们可能会犯严重的错误,此时他们都欣喜若狂。
Mrs. McDaniel, who had not left her house for several months except to see her doctors, began going to movies and restaurants every day.
麦克丹尼尔女士除了去医院就诊之外,已经几个月没有出过家门了,自从用了这种药,她可以每天出门,去电影院看电影,去餐馆就餐。
On Sept. 2, she and her husband went to the Heirloom Restaurant, in the middle of horse country, to celebrate their 50th wedding anniversary.
9月2日,她和丈夫一起去了市中心的Heirloom餐厅,庆祝他们50周年结婚纪念日。
She had given away so many of her clothes when she thought she was dying that she puzzled over what to wear. She had a favorite blouse that was loosefitting and comfortable, but Mr. McDaniel recalled, “It was long gone.” She could not drink wine with the medicines she was taking, so she and her husband sipped iced tea in the quiet dining room.
她以为自己快不行了,所以许多衣服都已经送人,结果到了结婚纪念日这天她都不知道应该穿什么。她有件很喜欢的外套,穿起来宽松又舒适,但丈夫记起来,“那件衣服早就送人了。”因为服用药物期间不能喝酒,于是她和丈夫在安静的餐厅喝着冰茶。
“We reminisced, but also talked about the future as we hoped it would be,” Mr. McDaniel said.
“我们回忆往昔,但也在畅想我们共同希望的未来,”麦克丹尼尔先生说。
But the reprieve lasted only weeks. By the end of September, the cancer was back.
但是病情的缓解只持续了几个星期。到了九月底,癌症又一次复。
Dr. McDaniel did not want to give up. Mrs. McDaniel’s tumor was sequenced again, looking for a new mutation, but there was nothing striking. As Dr. McDaniel sifted through the data, he called his parents every day. They began calling him the governor, hoping he would bring his mother another stay of execution.
麦克丹尼尔博士不想放弃。他安排给母亲的肿瘤再次测序,以便寻找新的基因突变,但却没有发现显著的线索。他每天拼命筛选分析数据,同时打电话给他的父母。他们称他为州长,希望他会给母亲带来另一次死缓通知。
The doctors considered a less appealing target, a mutated gene that T cells use to stop growing. Unpublished studies in mice suggested that a kidney cancer drug might stop the growth of T cells with this mutation.
几位研究者在测序数据中找到了一个不太重要的基因靶点,这是一个抑癌基因(抑制T细胞增长的基因)的突变。有几宗未发表的研究报告表明,在实验小鼠体内,带有这个基因突变的T细胞,在一种治疗肾癌的药物作用下能够停止增长。
By then, Mrs. McDaniel’s body was ravaged by the cancer and her treatments. She had entered hospice care, with a hospital bed in her home and a nurse and an assistant to help.
此时,麦克丹尼尔女士的身体在癌症和各种药物的猛攻下已经彻底垮掉了。她家里安置了医院的特护病床,在一名护士和一名助手的帮助下,她进入了临终关怀期。
“We had this shaky evidence, based on the genome and on unpublished data,” Dr. McDaniel said.
“根据基因组测序的数据和未发表的研究论文,我们找到了不太可靠的证据,”麦克丹尼尔博士说。
But the drug’s side effects were mild, and her family and doctors decided she should try it.
新药的副作用不大,家人和医生决定给她试用这个药。
“If we do nothing, she will be dead in one to six weeks,” Dr. McDaniel explained.
“就算我们什么都不做,她也只能再活一到六个星期了,”麦克丹尼尔博士解释说。
Mrs. McDaniel took the drug on Nov. 26. But she was so ill that she was unable to get out of bed, unable to drink from a straw. Her son Tim took his children to her bedroom one at a time so they could say goodbye.
麦克丹尼尔女士在11月26日拿到了药。但是她已经病得下不了床,连用吸管喝水都喝不进去了。儿子蒂默西把三个孩子逐个领进她的卧室,和她道别。
“She wasn’t talking, but her eyes were open, and she acknowledged each one with a weak chuckle,” Dr. McDaniel said.
“她说不了话了,但眼睛睁着,看到每个孩子时会轻轻笑一声,表示认得出他们,”麦克丹尼尔博士说。
Three days later, she briefly rallied. Her husband held her hand.
三天后,她短暂地回光返照。丈夫一直握着她的手。
“She said, ‘I love you,’ ” Mr. McDaniel said. “She then repeated it twice more. I kissed her forehead and told her that I loved her. Those were our last words to each other.”
“她说了声,‘我爱你’,”麦克丹尼尔先生说。“然后又重复了两遍。我亲吻她的额头,告诉她我爱她。这就是我们彼此说的最后一句话。”
The next morning, Nov. 30, Mr. McDaniel woke early and went to his wife’s room. Her breathing had become erratic. Worried, he stepped out and asked the hospice nurse to call the doctor. “In the seconds that I was absent, she died,” Mr. McDaniel said.
第二天早晨,11月30日,麦克丹尼尔先生很早就醒了,他走进妻子的房间,发现她的呼吸变得不规律。他忧心忡忡地走出房间,让临终关怀的护士打电话给医生。“在我走出房间的那几秒钟里,她走了,”麦克丹尼尔先生说。
The team that tried to save her was heartbroken too, and was left with a long list of what-ifs. “If you really look at it, what did we buy her?” Dr. de Castro asked. Mrs. McDaniel was dying last January. Yet would she have survived as long even without the sequencing or the drugs? Did the team make a difference?
试图救治她的研究人员们也心碎不已,留给他们的是一长串的假设。“好好回想一下,我们究竟为她争取到了什么?”德卡斯特罗博士问。在去年一月,麦克丹尼尔女士一度生命垂危。如果没有基因测序或这些新药治疗,那么她的生命能延长到11月吗? 研究人员的这种新治疗方法对她有实际意义吗?
“I hope we did,” Dr. de Castro said, “but it’s hard to know.”.
“我希望我们真的帮到她了,”德卡斯特罗博士:“但我真的很不确定。”