Job titles of the future: Nature’s drug designer

未来职业：自然界的药物设计师

In 2018, after nearly two decades working in Big Pharma, chemist Tim Cernak was ready to put his skills to a new use. For Merck, he’d developed precision therapies for cancer, HIV, and diabetes that could target disease while minimizing harm to healthy cells. But as a lifelong nature lover, he was increasingly concerned about the health of ecosystems and wondered whether his expertise could transfer. 2018年，在大型制药公司工作了近二十年后，化学家蒂姆·瑟纳克（Tim Cernak）准备将自己的技能用于新的领域。在默克公司（Merck）工作期间，他曾开发过针对癌症、艾滋病和糖尿病的精准疗法，这些疗法能够在靶向疾病的同时，最大限度地减少对健康细胞的伤害。但作为一名终身的自然爱好者，他越来越关注生态系统的健康，并思考自己的专业知识是否可以迁移到这一领域。

Animals, he learned, are often treated with pharmaceuticals formulated for humans, which affect them like old-school cancer drugs: Though intended to kill abnormal cells, they’re indiscriminate in the harm they cause. For instance, the standard of care for frogs infected with a deadly skin infection is itraconazole, an antifungal that is often lethal for the amphibian. Cernak imagines a world where “the patient was always meant to be a frog in the first place, from the beginning to the end.” Now an associate professor at the University of Michigan, he’s worked on all types of creatures, from a Gila monster with a parasite to bald eagles with avian flu. Here’s what it takes to treat nature’s patients. 他了解到，动物通常被施以专为人类配制的药物，这些药物对它们的影响就像老式的抗癌药物一样：虽然旨在杀死异常细胞，但它们造成的伤害是不分青红皂白的。例如，治疗感染致命皮肤病的青蛙的标准方案是伊曲康唑（itraconazole），这是一种抗真菌药物，但对两栖动物来说往往是致命的。瑟纳克设想了一个世界，在那里“患者从始至终都被设定为青蛙”。如今，作为密歇根大学的副教授，他已经治疗过各种各样的生物，从患有寄生虫的希拉毒蜥（Gila monster）到感染禽流感的秃鹰。以下是治疗自然界患者所需的条件。

Experience with protein-modeling software 蛋白质建模软件的经验

Developing any type of drug is extremely expensive, failure-prone, and slow-going. But AI can speed up the entire drug-design workflow, says Cernak. Google DeepMind’s AlphaFold model allows him to visualize a mutant protein’s three-dimensional structure on a screen—rather than growing it on a plate, the traditional methodology—and then quickly generate possible new drugs that would latch onto that structure. The next step is to run a series of reactions and see which potential drugs may be effective; with the help of robots in the lab, he can speed through as many as 1,500 per day. 开发任何类型的药物都极其昂贵、容易失败且进展缓慢。但瑟纳克表示，人工智能可以加速整个药物设计的工作流程。谷歌DeepMind的AlphaFold模型使他能够在屏幕上可视化突变蛋白质的三维结构——而不是像传统方法那样在培养皿中培养它——然后快速生成可能与该结构结合的新药。下一步是进行一系列反应，观察哪些潜在药物可能有效；在实验室机器人的帮助下，他每天可以处理多达1500种药物。

Curiosity about creatures of all sizes 对各种体型生物的好奇心

Cernak isn’t selective with his patients. For example, he worked on a treatment for loggerhead sea turtles after he was shocked to learn that the iconic species suffered from contagious tumors. He feels especially drawn to creatures that have helped humans, like the Gila monster, whose hormones have informed popular weight-loss drugs like Ozempic. And it’s not just animals; he’s also developing a precision insecticide to treat hemlock trees under attack from invasive species. 瑟纳克对患者并不挑剔。例如，在得知红海龟这种标志性物种正遭受传染性肿瘤的困扰后，他感到非常震惊，并着手研究治疗方案。他特别被那些曾帮助过人类的生物所吸引，比如希拉毒蜥，其激素为Ozempic等热门减肥药提供了研发思路。不仅是动物，他还在开发一种精准杀虫剂，用于治疗受到入侵物种侵害的铁杉树。

A pioneering spirit 开拓精神

Cernak refers to this new discipline as “conservation chemistry.” It’s a combination of words with a loaded history, from DDT decimating US bald eagle populations in the 1960s, to cow painkillers killing millions of Indian vultures in the ’90s. He recognizes the risks, but Cernak feels that excluding chemists from conservation is a missed opportunity. “I’m just sick of looking at the chemical tools that are used in the conservation space, and they’re not cutting-edge,” he says. “It’s like, how do you have this super high-tech engine over here for making human medicines, while we’re living through a mass extinction?” 瑟纳克将这一新学科称为“保护化学”（conservation chemistry）。这是一个带有沉重历史背景的词汇组合，从20世纪60年代滴滴涕（DDT）导致美国秃鹰数量锐减，到90年代牛用止痛药导致数百万印度秃鹫死亡。他认识到其中的风险，但瑟纳克认为，将化学家排除在保护工作之外是一个错失的机会。“我厌倦了看到保护领域使用的化学工具，它们根本不是尖端的，”他说。“这就好比，我们这边有制造人类药物的超高科技引擎，而我们却正经历着一场大规模物种灭绝，这怎么说得过去？”