This scientist is helping build a missing map of childhood
This scientist is helping build a missing map of childhood
这位科学家正在帮助绘制一张缺失的儿童发育图谱
In 2017, Deanne Taylor attended a presentation at the University of Pennsylvania, just a short walk from her office. A researcher was there to unveil the Human Cell Atlas, an ambitious project that aimed to map every cell in the human body. Taylor was floored, and then concerned. As details emerged, she discovered that the project’s researchers had only made plans to study adults. “That’s when my little alarm went off,” she says. “Not again.”
2017年，迪安·泰勒（Deanne Taylor）在宾夕法尼亚大学参加了一场演讲，会场离她的办公室仅几步之遥。当时，一位研究人员正在展示“人类细胞图谱”（Human Cell Atlas），这是一个旨在绘制人体内每一个细胞的宏大项目。泰勒起初感到震惊，随后便忧心忡忡。随着细节披露，她发现该项目的研究人员竟然只计划研究成年人。“那一刻，我心中的警铃响了，”她说，“又是这样。”
Since joining the Children’s Hospital of Philadelphia (CHOP) as the director of bioinformatics three years earlier, Taylor had been disappointed by the lack of investment in medical research focused on children. The dominant view, she says, was that children are exactly like small adults. They’re not. Children’s cells are different from grownups’ cells in the way they express genes—switching them on and off or turning them up or down. Those variations can cause drastically different and even deadly responses to drugs that adults tolerate well.
自三年前加入费城儿童医院（CHOP）担任生物信息学主任以来，泰勒一直对医学界在儿童研究领域投入不足感到失望。她说，当时主流观点认为儿童只是“缩小版的成人”。事实并非如此。儿童细胞与成人细胞在基因表达方式上存在差异——即基因的开启与关闭，或表达水平的高低。这些差异可能导致儿童对成人能够耐受的药物产生截然不同、甚至致命的反应。
The 2017 talk was the moment Taylor didn’t know she’d been waiting for. She quickly channeled her concern into a campaign, joining the Human Cell Atlas’s volunteer team and helping write a section on children for a white paper outlining the group’s goals and plans. She then rallied a cross-hospital coalition of pediatric researchers to contribute to the project and spearheaded a 2019 paper that outlined the case for studying children—a bid to attract more interest and funding to the field. “It put a flag in the ground,” she says. “Why don’t we have healthy models of children’s development?”
2017年的那场演讲，成为了泰勒一直在等待的契机。她迅速将担忧转化为行动，加入了“人类细胞图谱”的志愿者团队，并协助撰写了白皮书中关于儿童的部分，阐述了该组织的目标与计划。随后，她召集了一个跨医院的儿科研究人员联盟为该项目做出贡献，并牵头发表了2019年的一篇论文，论证了研究儿童的必要性，旨在吸引更多关注和资金投入该领域。“这就像是在这片土地上插下了一面旗帜，”她说，“为什么我们还没有健康的儿童发育模型呢？”
So far, the push has paid off. In 2021 the NIH awarded a $38.5 million grant to the Developmental Genotype-Tissue Expression Project (dGTEx), a major initiative aimed at establishing the first comprehensive database of healthy pediatric tissue. The project banks samples collected from otherwise healthy children who have died and whose parents agreed to donate their bodies, and maps how genes across all the major organ systems are expressed.
到目前为止，这些努力已见成效。2021年，美国国立卫生研究院（NIH）向“发育基因型-组织表达项目”（dGTEx）拨款3850万美元，这是一项旨在建立首个健康儿科组织综合数据库的重大举措。该项目收集了因意外去世但身体健康的儿童样本（经其父母同意捐赠），并绘制了所有主要器官系统的基因表达图谱。
Taylor and her team curate and standardize the information associated with each tissue donation, including family history and details about the samples. A separate group does analysis on the samples themselves, and then all the information is combined to create a database—a baseline of what gene expression looks like in children. It’s the first step to enabling research that could advance our knowledge of normal development, disease, drug effectiveness, and other phenomena.
泰勒和她的团队负责整理和标准化与每份组织捐赠相关的信息，包括家族病史和样本细节。另一个小组则负责对样本本身进行分析，随后将所有信息汇总，建立起一个数据库——即儿童基因表达的基准线。这是推动相关研究的第一步，有望加深我们对正常发育、疾病、药物有效性及其他现象的认知。
The dGTEx team will eventually feed its data into the Human Cell Atlas, which, thanks to Taylor and many of the coauthors of the 2019 paper, now includes a pediatric section. Taylor’s primary responsibility may be collecting and organizing data for dGTEx, but colleagues say she’s also the glue holding diverse research projects together. That’s especially important for the Human Cell Atlas, which depends on contributions from a loose coalition of researchers, all pursuing their own objectives.
dGTEx团队最终会将数据整合进“人类细胞图谱”。多亏了泰勒和2019年那篇论文的许多合著者，该图谱现在已经包含了一个儿科部分。泰勒的主要职责或许是为dGTEx收集和整理数据，但同事们认为，她也是将各种研究项目凝聚在一起的“粘合剂”。对于依赖于一个松散的研究人员联盟（每个人都在追求各自的目标）的“人类细胞图谱”而言，这一点尤为重要。
“Deanne took a big-picture view and said, We don’t just need to understand the pediatric kidney or the pediatric brain or the pediatric immune system. We need a holistic view of pediatric development,” says Sarah Teichmann, a cofounder of the Human Cell Atlas. “She embodies that interdisciplinary spirit.”
“迪安拥有宏观视野，她说：我们不仅需要了解儿科肾脏、儿科大脑或儿科免疫系统，我们需要的是对儿童发育的整体视角，”人类细胞图谱的联合创始人莎拉·泰希曼（Sarah Teichmann）表示，“她体现了那种跨学科的精神。”
A healthy baseline
健康的基准线
Taylor describes her career as a “random walk,” driven by a singular intensity she now attributes to undiagnosed autism and ADHD. At five, she began reading her mom’s medical texts. By 12, she was checking out physics books from the library. Physics provided mysteries to solve, and she wanted to understand how things worked.
泰勒将自己的职业生涯描述为一场“随机漫步”，其动力源于一种独特的专注力，她现在将其归因于未被诊断出的自闭症和多动症（ADHD）。五岁时，她就开始阅读母亲的医学教材。到了12岁，她已经开始从图书馆借阅物理学书籍。物理学提供了待解的谜题，而她渴望理解事物运作的原理。
Taylor got her PhD in biophysics, in 2001, but was inspired by the then-active Human Genome Project to change gears and take on a postdoc at Pfizer，writing code to handle complex data in rare-disease research. Then she moved to reproductive medicine, where she worked on some of the first computer programs to screen embryos for chromosomal abnormalities—many of which are still in use today.
泰勒于2001年获得生物物理学博士学位，但受当时正在进行的人类基因组计划启发，她改变了方向，在辉瑞公司从事博士后研究，编写代码以处理罕见病研究中的复杂数据。随后，她转向生殖医学领域，参与开发了首批用于筛查胚胎染色体异常的计算机程序——其中许多程序至今仍在使用。
Despite this seemingly winding road, Taylor says her focus has always been on understanding why the same illness hits people differently. How can two people carry the same disease-associated gene variant, but only one get sick? The Human Cell Atlas—including all the data feeding into it from dGTEx and other projects—could at last help researchers find answers.
尽管这条道路看起来曲折，但泰勒表示，她的核心关注点始终是理解为什么同一种疾病对不同人的影响各不相同。为什么两个人携带相同的疾病相关基因变异，却只有一个人发病？“人类细胞图谱”——包括来自dGTEx和其他项目的所有数据——最终可能帮助研究人员找到答案。
The effort is a natural extension of the Human Genome Project. That initiative, which wrapped up in 2003, helped researchers link specific genes to specific diseases. But a map of the genome is a bit like a DIY kit with all the parts and no assembly manual. It doesn’t tell you where and how cells use each gene throughout the body. After all, “we’re just older kids,” Taylor says. “By ignoring the pediatric side of things, I think people are missing a window of intervention in human disease.”
这项工作是人类基因组计划的自然延伸。该计划于2003年结束，帮助研究人员将特定基因与特定疾病联系起来。但基因组图谱就像一套只有零件却没有组装说明书的DIY工具包。它无法告诉你细胞在全身各处如何使用每一个基因。毕竟，“我们只是长大了的孩子，”泰勒说，“我认为，忽视儿科领域，意味着人们错过了一个干预人类疾病的窗口期。”
For that, you need to know how the genes are expressed. Gene expression generally involves making a protein that does a specific job in the body, like building tissue or sending signals. Unlike DNA, which largely remains the same throughout our lives, the way the genes in DNA are expressed changes as we develop. Differences in gene expression can determine whether a therapy will work—or could harm more than it helps.
为此，你需要了解基因是如何表达的。基因表达通常涉及制造一种在体内执行特定功能的蛋白质，例如构建组织或发送信号。与DNA在人的一生中基本保持不变不同，DNA中基因的表达方式会随着我们的发育而改变。基因表达的差异可以决定一种疗法是否有效，或者是否会弊大于利。
Because of the way cardiac genes are expressed in children, chemotherapy drugs can attack not only tumors but also children’s developing hearts, potentially causing lifelong damage. Other treatments can affect the entire body, sometimes triggering a reversible but potentially fatal immune-system reaction called cytokine release syndrome.
由于儿童心脏基因的表达方式特殊，化疗药物不仅会攻击肿瘤，还会攻击儿童正在发育的心脏，可能造成终身损害。其他治疗方法则可能影响全身，有时会引发一种可逆但可能致命的免疫系统反应，即细胞因子释放综合征。
The dGTEx database aims to create a baseline for gene expression in children—a molecular map of how the body’s roughly 20,000 genes do their work in healthy tissue cells. It is only one of the collaborations Taylor manages. She’s a principal investigator for the Kids First Data Resource Center, which sequences…
dGTEx数据库旨在为儿童基因表达建立基准线——这是一张分子图谱，展示了人体约2万个基因如何在健康组织细胞中发挥作用。这只是泰勒管理的众多合作项目之一。她还是“儿童优先数据资源中心”（Kids First Data Resource Center）的首席研究员，该中心负责对……进行测序。