A recent article in Journal of Experimental Medicine by Susan Weiss on ‘Forty years with coronaviruses’ is very informative and gives the history of research in this expanding field in a time of pandemic (1). In her Fig. 1, a timeline of these forty years of research is presented with two pathogenic human coronaviruses named for the early years 1960–1970. There are, however, no references given to the origin of these strains.

Who were behind the isolation of these two coronaviruses in Fig. 1, OC43 and 229E (1)? The first one, OC43, was isolated and detected by Kenneth McIntosh et al. working at NIH, Bethesda, Maryland, USA (2). He was using an organ culture method and refers to Hoorn and Tyrrell for this technique (3). The second coronavirus in the timeline, 229E, was isolated and described by Almeida and Tyrrell (4). They also described a similar virus isolated earlier (5), B814, and the excellent electron microscopic images by June Almeida later led to the name corona (6). These two strains were very early coronaviruses isolated from human sources, and this reference is often given for the first isolation of coronavirus in man. However, as rightly pointed out by Elisabeth Mahase in British Medical Journal of this year (7), the very first description was for the one just mentioned, strain B814, and in the very same journal, BMJ (5). It is, however, very interesting to note that the method of isolation used in all these early investigations was the organ culture method of Hoorn (8), a fact that is often overlooked.

The organ culture method used was described by Hoorn and by Hoorn and Tyrrell (8, 9). Dr David Tyrrell was the head of the famous ‘Common Cold Research Unit’, Salisbury, England, run by Medical Research Council, MRC, England. But who was Hoorn?

Dr Bertil Hoorn was a Swedish ENT medical doctor who got intrigued by common colds and their causative agents. He had a true explorative mind and he returned to the basic sciences and started a research project at the Department of Medical Microbiology, University of Lund, Lund, Sweden. The department had earlier seen both professor John Forssman (discoverer of the Forssman antigen) and professor Arvid Lindau (von Hippel-Lindau disease) as heads of the department. The professor and head in the 1960s was Rune Grubb, who discovered the inheritable Gm groups of the immunoglobulins.

At the same time we, the present authors, were young medical students with interest in microbiology who had joined the same department. We got to know Bertil Hoorn quite well and one of us, E.N., even shared laboratory space. Bertil Hoorn worked hard on setting up organ cultures of tracheal tissue. With synthetic media, he managed to keep the organs alive with beating ciliae. He presented his innovation at meetings and in a scientific article (8). Dr David Tyrrell heard about the novel technique and invited Bertil Hoorn to set up his method at the Common Cold Research Unit in Salisbury. Bertil Hoorn accepted the invitation and loaded his Citroen car with all the equipment and reagents needed and drove to England. After initial problems with water quality, the method was working well. Together with David Tyrrell, Bertil Hoorn then published several papers on the successful isolation of upper respiratory tract viruses using this new method (3, 9-12).

Back in Lund, Bertil Hoorn also worked on his academic career and wrote his PhD thesis in 1966 which was successfully defended at a public dissertation (13). His laboratory at the department was located in a wing where the virologists had set up their quarters (Fig. 2).

Dr David Tyrrell in Salisbury continued to use the new organ culture method, and in 1967, he described the two coronaviruses isolated from cases of human infections (4). His coworker, June Almeida, was the very best electron microscopist at the time.

So the two strain names mentioned in the review by Susan Weiss and the first coronavirus isolated as described by Elisabeth Mahase had a further history, leading to an innovative young Swedish medical doctor, Bertil Hoorn, later professor of medical virology in Umeå, Sweden, who laid the methodological foundation for research on coronavirus infections in humans. This part of the history is also worth mentioning and to remember.

苏珊·韦斯最近在《实验医学杂志》上发表的一篇关于“冠状病毒四十年”的文章非常有用，并介绍了大流行时期这一不断扩大的领域的研究历史 ( 1 )。在她的图 1 中，展示了这 40 年研究的时间表，其中展示了两种以 1960 年至 1970 年早期命名的人类致病冠状病毒。然而，没有提到这些菌株的起源。

图 1、OC43 和 229E ( 1 )中这两种冠状病毒的分离背后是谁？第一个是 OC43，由 Kenneth McIntosh 等人分离并检测到。在美国马里兰州贝塞斯达 NIH 工作 ( 2 )。他使用了器官培养方法，并参考了 Hoorn 和 Tyrrell 的这项技术 ( 3 )。时间线中的第二种冠状病毒 229E 是由 Almeida 和 Tyrrell 分离并描述的 ( 4 )。他们还描述了一种较早分离的类似病毒（5），B814，后来琼·阿尔梅达（June Almeida）出色的电子显微镜图像导致了日冕这个名字（6）。这两种毒株是从人源中分离出来的非常早期的冠状病毒，这一点常被用于首次在人体内分离出冠状病毒。然而，正如 Elisabeth Mahase 在今年的英国医学杂志 ( 7 ) 中正确指出的那样，第一个描述是针对刚刚提到的菌株 B814，以及在同一期刊 BMJ ( 5 ) 中。然而，非常有趣的是，在所有这些早期研究中使用的分离方法是 Hoorn ( 8 )的器官培养方法，这一事实经常被忽视。

使用的器官培养方法由 Hoorn 以及 Hoorn 和 Tyrrell 描述 ( 8, 9 )。David Tyrrell 博士是英国索尔兹伯里著名的“普通感冒研究单位”的负责人，该单位由英国 MRC 医学研究委员会管理。但霍恩是谁？

Bertil Hoorn 博士是一位瑞典耳鼻喉科医生，他对普通感冒及其病原体很感兴趣。他有一颗真正的探索精神，回到基础科学，在瑞典隆德大学医学微生物学系开始了一个研究项目。该系早些时候曾将 John Forssman 教授（Forssman 抗原的发现者）和 Arvid Lindau 教授（von Hippel-Lindau 病）都任命为系主任。1960 年代的教授和负责人是 Rune Grubb，他发现了免疫球蛋白的可遗传 Gm 组。

同时，我们，现在的作者，是对微生物学感兴趣的年轻医学生，他们加入了同一部门。我们非常了解 Bertil Hoorn，我们中的一个人 EN 甚至共享实验室空间。Bertil Hoorn 努力建立气管组织的器官培养。使用合成媒体，他设法通过跳动纤毛使器官保持活力。他在会议和一篇科学文章中介绍了他的创新（8）。David Tyrrell 博士听说了这项新技术，并邀请 Bertil Hoorn 在索尔兹伯里的普通感冒研究中心建立他的方法。Bertil Hoorn 接受了邀请，将他的雪铁龙汽车装上所需的所有设备和试剂，驱车前往英国。在最初出现水质问题后，该方法运行良好。随后，Bertil Hoorn 与 David Tyrrell 一起发表了几篇关于使用这种新方法成功分离上呼吸道病毒的论文 ( 3, 9-12 )。

回到隆德，Bertil Hoorn 也开始了他的学术生涯，并于 1966 年撰写了他的博士论文，并在一篇公开论文中获得成功答辩 ( 13 )。他在该部门的实验室位于病毒学家设立宿舍的一侧（图 2）。

索尔兹伯里的 David Tyrrell 博士继续使用新的器官培养方法，并于 1967 年描述了从人类感染病例中分离出的两种冠状病毒 ( 4 )。他的同事琼·阿尔梅达 (June Almeida) 是当时最好的电子显微镜专家。

因此，Susan Weiss 在评论中提到的两个菌株名称和 Elisabeth Mahase 描述的第一种分离的冠状病毒有着更深的历史，导致了一位创新的年轻瑞典医生 Bertil Hoorn，后来在瑞典于默奥担任医学病毒学教授，他为研究人类冠状病毒感染奠定了方法学基础。这部分历史也值得一提和记住。