Many of you in the audience are just beginning your careers as physician-scientists. And most of you, I suspect, are struggling with the question of how can I do something worthwhile in biomedical research. The answer to your struggles may be found in a provocative sculpture created by the contemporary African American artist Martin Puryear (Figure 1).

Ladder for Booker T. Washington. Martin Puryear. 1966. Wood (ash and maple). 36 × 1.9 feet (narrowing at top to 3 inches). Collection of the Modern Art Museum of Fort Worth. Gift of Ruth Carter Stevenson, by Exchange.

Puryear’s sculpture is a tall wooden ladder (36 feet high) suspended by invisible wires, enabling it to float from the ceiling of the atrium of the Museum of Modern Art in Fort Worth. Puryear constructed the ladder from a single oak tree. The bottom rung is 2 feet wide, and the top rung is 1 inch wide. There are 100 rungs, most of which are at the top and not visible in the photograph. The narrowing of the ladder towards the top creates a distorted visual perspective that evokes an illusionary goal that is unattainable. It is easy to get both feet on the first rung of the ladder, but it is an almost impossible struggle to reach the top. Opportunity narrows at the very highest reaches.

Puryear created this work to symbolize the struggles of Booker T. Washington, who was the dominant African American figure in the U.S. in the early 1900s. Booker T. Washington was born into slavery in 1856, was freed at age 9, and by age 25 had established the Tuskegee Institute in Alabama as a trade school for African Americans. His autobiography, Up from Slavery, is still read today, more than 100 years after it was written. Harvard University conferred an honorary degree on Washington in 1896 when he was only 40 years of age.

Puryear’s ladder can be thought of as a universal metaphor for everyone who struggles to do something worthwhile. But there’s another way to think about the ladder that may be more relevant to beginning physician-scientists (Figure 2). If we turn the Booker T. Washington ladder upside down, the difficult challenge is not at the top, but at the bottom — getting your little toe on the first rung. Here the ladder symbolizes the struggles of physician-scientists like Barry J. Marshall, who made the totally unexpected discovery that peptic ulcers are caused not by stress, but by a bacterial Helicobacter infection that can be cured with antibiotics. Marshall got his first toe on the ladder by doing a bold experiment in 1985 that opened a new field, but virtually no one recognized the significance of his work when it was first published in the Medical Journal of Australia — not one of your high-profile journals!

Ladder for physician-scientists. Puryear’s Ladder has been turned upside down. Illustration by Nancy Heard; reproduced with permission of the artist.

The Barry J. Marshalls of the world who do truly original research have the first 94 rungs of the upside-down ladder all to themselves for many years until reaching the 95th rung — the 5th rung from the top — where there’s now room for other scientists to jump on the bandwagon and join in on the fun and excitement of a new venture. This is the tipping point when a new field of science or medicine explodes with widening opportunities and becomes widely recognized as important.

So what is the best way for a young physician-scientist to get his or her little toe on the first rung of the upside-down ladder? The key is to choose the right mentor. You don’t want a mentor who counts papers, who is focused on impact, or who seeks press conferences. What you want is a mentor who can teach you how to ask the right question. Asking and framing the right question — one that is original, interesting, and experimentally tractable — is the hardest thing to do in science. In my view, the biggest mistake that beginning scientists make is to follow the crowd, which means you will be asking the next incremental question — not a bold one.

To the beginning physician-scientists in the audience, I wish you all good luck and success in selecting a mentor who can teach you how to ask the right question. Remember, you can’t choose your parents, but you can choose your mentors.

Footnotes

Reference information: J Clin Invest. 2017;127(10):3576. https://doi.org/10.1172/JCI97405.

Remarks at the Presentation of the 2017 Donald Seldin~Holly Smith Award for Pioneering Research during the annual meeting of the American Society for Clinical Investigation and Association of American Physicians, Chicago, IL, April 22, 2017.

观众中的许多人刚刚开始您作为医师科学家的职业。我怀疑，你们中的大多数人都在为我该如何在生物医学研究中做一些有价值的事情而苦苦挣扎。奋斗的答案可以在当代非裔美国艺术家马丁·珀伊尔（Martin Puryear）创作的挑衅雕塑中找到（图1）。

布克·T·华盛顿的阶梯。马丁·珀伊尔。1966年。木材（白蜡木和枫木）。36×1.9英尺（从顶部缩小到3英寸）。沃思堡现代美术馆的收藏。交换给露丝·卡特·史蒂文森（Ruth Carter Stevenson）的礼物。

Puryear的雕塑是一根高高的木梯（36英尺高），由看不见的金属丝悬挂，使其可以从沃思堡现代艺术博物馆中庭的天花板上漂浮下来。Puryear用一棵橡树建造了梯子。底部梯级为2英尺宽，顶部梯级为1英寸宽。一共有100个梯级，其中大多数梯级位于顶部，在照片中不可见。梯子朝顶部变窄会产生扭曲的视觉效果，从而引起无法实现的幻觉目标。双脚踩到梯子的第一个梯级很容易，但要爬到顶部几乎是不可能的。机会在最高端逐渐缩小。

Puryear创作了这部作品，以象征布克·T·华盛顿的奋斗，他是1900年代初在美国占统治地位的非洲裔美国人。布克·T·华盛顿于1856年出生于奴隶制，在9岁时被释放，到25岁时，他在阿拉巴马州成立了Tuskegee学院，作为一所非洲裔美国人的贸易学校。他的自传《从奴隶制起来》至今仍在阅读中，距其写作已经有100多年的历史了。1896年，哈佛大学40岁时，他在华盛顿授予了荣誉学位。

对于所有努力去做有价值的事情的人来说，Puryear的阶梯可以被认为是一个普遍的隐喻。但是，还有另一种思考阶梯的方式可能与初级医师科学家更为相关（图2）。如果我们将布克·T·华盛顿梯子颠倒过来，那么困难的挑战就不在顶部，而在底部–将您的小脚趾放在第一个梯级上。在这里，梯子象征着像巴里·J·马歇尔（Barry J. Marshall）这样的医师科学家的努力，他完全出乎意料地发现消化性溃疡不是由压力引起的，而是由细菌性幽门螺杆菌引起的。可以用抗生素治愈的感染。马歇尔（Marshall）于1985年进行了一次大胆的实验，从而开拓了一个新领域，这使他的第一只脚趾踏上了台阶，但实际上，没有人意识到他的工作的重要性，因为该工作首次在《澳大利亚医学杂志》上发表，而不是您的知名度高的一个。期刊！

医师科学家的阶梯。Puryear的阶梯已经被颠倒了。Nancy Heard的插图；经艺术家许可转载。

世界上真正从事原创研究的Barry J. Marshalls拥有多年以来全部94头上下颠倒的梯子，直到到达第95梯级（从上到下的第5梯级）为止，现在这里还有其他科学家的空间赶上潮流，加入新企业的乐趣和兴奋。这是一个新的科学或医学领域爆发的机会越来越大，并被广泛认为是重要的转折点。

那么，年轻的医师科学家将自己的小脚趾放在颠倒的阶梯的第一梯级上的最佳方法是什么？关键是选择合适的导师。您不希望导师计数论文，关注影响力或寻求新闻发布会。您想要的是一位可以教您如何提出正确问题的指导者。提出和提出正确的问题-一个原始的，有趣的并且在实验上易于处理的问题-是科学界最难的事情。在我看来，新手科学家犯的最大错误是关注人群，这意味着您将要提出下一个渐进的问题，而不是一个大胆的问题。

对于听众中刚开始的医师科学家们，祝大家选择一个能教您如何提出正确问题的导师，祝您好运和成功。请记住，您不能选择父母，但可以选择您的导师。

脚注

参考信息：J Clin Invest。2017; 127（10）：3576。https://doi.org/10.1172/JCI97405。

在2017年4月22日于美国芝加哥举行的美国临床研究学会和美国医师协会年会上，发表2017年Donald Seldin〜Holly Smith杰出研究奖颁奖典礼。