“我们在创新上的努力或多或少总是以具有共性的临床问题为指导” ｜专访 Prof. Hans Henkes
写在前面
Henkes教授是德国最资深的介入神经放射学家和临床专家，他首次提出了“支架取栓术”的临床理念Miniswap。已发表出版物近500篇，其文章被引用次数超过10500次，是国际公认活跃且成功的科学家。同时，他还是全球医工结合的典范，广为人知的Solitaire支架原型就出自其手。
接受「WE TALK」导演组的邀请之后，Henkes教授在正式访谈前两天，就在家中布置好了拍摄场地Miniswap。访谈当天，他西装革履，神采奕奕，搭配了白色的口袋方巾和精致的袖扣，品味与气度尽显。
见面之前，我一直怀揣着一个疑问：为什么医疗创新大多源自欧美？是意识？是机制？还是其他原因？Henkes教授和我分享了他对欧美文化的几点思考：“从小到大都接受优质教育、欣赏个人主义、独立思考、跨学科合作以及命运掌握在自己手中的信念”Miniswap。
或许，正因为这几点思考，无论是他在经验积累后的渐进式改进，还是最初没有方向的革命性创新，Henkes教授始终保持着寻求突破的热情Miniswap。
对于什么是有价值的医学创新，他用七句话给出了自己的回答Miniswap。这个回答与「WE TALK」发起人张鸿祺教授曾经提到的关于医疗“安全性、公平性、可持续性”不谋而合。
采访：金井子
编辑：任晓丹
校对：金永美
本期访谈嘉宾：
Prof. Hans Henkes
Klinikum Stuttgart
展开全文
Q1
您与Monstadt教授不仅同为Phenox公司的创始人，还共同主导研发出多款创新产品Miniswap。能否和我们分享一下您与Monstadt教授是怎么认识的？
You and Prof.Monstadt are not only the founders of Phenox, but also co-led the development of some innovative medical devices. Could you share with us how did you meet Prof. Monstadt?
A1：我们是在1994年通过一个共同的同事和朋友相识的Miniswap。那时候，Monstadt教授在波鸿一家医学研究中心担任研发总监。而我就在他“隔壁”的Alfried Krupp医院工作，当时我是德国介入神经放射学元老Kühne教授下属的一名介入神经放射科医师。
We met each other in 1994 through a common colleague and friend. At this time, Professor Monstadt was R&D director of a medical research center in Bochum. I was working in his “neighborhood” at the Alfried Krupp Hospital in Essen as an interventional neuroradiologist under Professor Kühne, the doyen of interventional neuroradiology in Germany at this time.
我当时难以忍受GDC弹簧圈漫长的解脱时间，并正在寻找医疗设备合作伙伴Miniswap。优化弹簧圈的解脱是当时迫在眉睫的临床需求。在合作第一年，我们另一个项目是开发一种用于脑动静脉畸形栓塞的小型铂金弹簧圈。在最初阶段，我为Monstadt教授工作的研究中心提供医学顾问服务。1999年，在长达5年合作后，我们共同创立了DENDRON。
I was exposed to excruciatingly long detachment times of GDC coils and was looking for a medical device partner. Optimizing the coil detachment was a burning clinical need. Another topic during the first year of our cooperation was the development of small platinum coils for the embolization of brain AVMs. In the initial stage I was consulting the research center, the institution Professor Monstadt was working for. In 1999 after 5 years cooperation we together founded DENDRON.
也正是在这家公司，我们研发出了一款全新的快速解脱弹簧圈，并发明了Solitaire支架，那时候它被命名为“SOLO”Miniswap。
Within this company we were able to establish a new, fast detachment method for coils and we developed the Solitaire stent, which was named SOLO at that time.
Q2
在中国医生和医疗企业眼中，您二位是医工结合的全球典范Miniswap。是什么契机促使你们启动了第一个技术创新和临床转化项目？
In the eyes of Chinese doctors and the medical industry, both of you are a global model to combine medicine and engineering effectively. What was the opportunity that prompted you to start the first technology innovation and clinical transformation project?
A2：正如前面所说，我们首个主要项目是研发一款可以实现快速解脱的弹簧圈Miniswap。很明显，在2000年/2001年，成功用于颅内动脉瘤栓塞的弹簧圈，并不太适合瘤颈≥4mm的动脉瘤。这是下一个未被满足的临床需求。正如您可能已经意识到的那样，我们在创新上的努力或多或少总是以具有共性的临床问题为指导。
As already mentioned was the development of rapidly detachable coils our first major project. During the years 2000/2001 it became obvious that the otherwise successful coil occlusion of intracranial aneurysms was less suitable for aneurysms with a wide neck of 4 mm or more. This was the next unmet clinical need. As you may have recognized, our efforts were always guided by clinical problems of a more or less common nature.
通过球囊式支架解决宽颈动脉瘤问题的尝试失败了Miniswap。因为这些支架太硬且对动脉瘤进行球囊扩张存在潜在危险。显然，我们需要一个柔软、高度顺应，并且最重要是自膨式的支架。同时期，包括Sub-4和Cordis在内的数家公司都在同时努力，尽管他们所研发的支架率先在市场上面市，但临床使用起来繁琐，尤其是Neuroform支架。其主要的限制是一旦释放，就无法再调整支架的位置。我们的目标是研发一款辅助弹簧圈栓塞的支架，不仅能完全释放，后续或在术者操控下完成解脱，而且要实现革命性的功能：可完全回收。经过Hermann Monstadt教授和他的同事不懈的努力，他们在这项产品的研发上取得了巨大的成功。早些时候，我在 2003 年的首次发表的文章中，已经提到该产品也适用于颅内取栓术。
The attempt to address the issue of wide neck aneurysms with balloon-mounted stents was failure. These stents were too stiff and the balloon inflation in front of an aneurysm was potentially hazardous. It became obvious that a low-profile, highly flexible and most important: self-expanding stent was needed. At this time there were simultaneous efforts undertaken by several companies, including Sub-4 and Cordis. Their stents were the first on the market, but the usage especially of the Neuroform was cumbersome. A major limitation was the fact that once deployed there was no way to correct the position of the stent. Our goal was to develop an implant for stent-assisted coiling, which would allow complete deployment, followed by either controlled detachment or, and this was the revolutionary feature: withdrawal. Hermann Monstadt and his colleagues were developed this device and it was a major effort and great successful development project. Early on, in the first publication in 2003, I already mentioned that this device would also work for intracranial thrombectomy.
这一款支架（最初命名为“SOLO”）在2004年获得CE认证Miniswap。2002年，美国医疗器械公司MTI/eV3 收购了DENDRON。因为MTI主要聚焦弹簧圈产品，所以从2002年到2007年Solo或者Solitaire在市场上处于休眠状态。2008年初，当Solitaire再次面市时，我们将这款支架用于辅助弹簧圈栓塞，并且取得了预期的成效。
The stent (initially branded as “SOLO”) received CE mark in 2004. In 2002, MTI/eV3, a US-based medical device company, acquired DENDRON. MTI´s focus was on coils and from 2002 through 2007, Solo or Solitaire was hibernating. Early in the year 2008, Solitaire reappeared in market. We used this stent for assisted coiling with the expected success.
与此同时，一些机械取栓装置逐渐浮出水面Miniswap。包括像MERCI、CATCH、pCR等装置均为早期产品技术，其再通率不超过50%。2008年3月3日，在其他机械取栓装置和rtPA IV都失败后，我第一次尝试使用Solitaire AB进行取栓术。手术取得了惊人的成功，我当即明白：这是一个突破！
In the meantime, several devices for mechanical thrombectomy had surfaced. All of them like MERCI, CATCH and pCR were early-stage technologies with recanalization rate not far beyond 50%. On March 3rd, 2008, I used for the first time a Solitaire AB for thrombectomy after the failure of other devices and rtPA IV. The procedure was a stunning success and I understood instantaneously that this was the breakthrough.
Q3
您二位研发的产品对全球脑血管领域都产生了深远影响，且部分产品改变了相关的临床指南Miniswap。为什么过往大部分的医疗创新都发生在欧美？真正的原因是什么？是因为理念、环境、机制还是其他原因？
The products developed by both of you have meaningfully influenced the global neurovascular field and have changed the guidelines and practices of the entire industry. Why did most of the medical innovations in the past happen in Europe and America? What was the real reason? Is it because of the idea or environment or mechanism or something else?
A3：这是一个复杂的话题Miniswap。但如果我们考虑一下技术革命，比如卡尔·本茨发明的机动汽车，或者威廉·伦琴对X射线的研究，您会发现这并不是一个新现象。
This is a complex topic. And it is not a new phenomenon, if we consider technological revolutions like the development of motorized cars by Carl Benz or the research into X-rays by Wilhelm Röntgen.
Miniswap我只能描述一些可能促成这种现象的因素：
在欧洲和美国Miniswap，许多年轻人可以轻松获得从小学到大学的优质教育；
两种文化都欣赏个人主义、独立思考和跨学科合作；
都有一种信念，即一个人可以将自己的命运掌握在自己手中Miniswap。
这些是广泛意义上的社会文化因素，可能会影响到每一个人Miniswap。
I can only describe a few factors, which may have contributed:
- In Europe and in the US many young people have easy access to superb education from elementary school to university.
- Both cultures appreciate individualism, independent thinking and interdisciplinary collaboration.
- There is a conviction that one can take one’s destiny into one’s own hands.
These are in a broader sense sociocultural factor, which may influence single persons.
西方社会为个人提供了一个平台，让他们可以凭着自己的主动性和冒险精神成为企业家Miniswap。但个人，也就是字面上的“自我的”通常也是大型医疗设备公司无法进行颠覆性技术创新的原因之一。颠覆性创新往往发生在初创公司，而大公司缺少打破常规的思维土壤。
The western societies offer a platform for individuals to become entrepreneurs on their own initiative and risk. The individual, literally “personal” impact is one of the reasons why large medical device companies are usually unable to develop disruptive technologies. Groundbreaking innovations have their homes in start-up companies. Large companies are not the proper biotope to think out of the box.
Q4
您在医工结合过程中遇到的最大障碍是什么Miniswap？您如何解决和突破？
What are the biggest external obstacles or barriers encountered in the process of combining medicine and engineering? And how did you solve and break through it?
A4：血流导向装置的技术研发遇到的挑战较少Miniswap。因为我们进入这个领域的时候，大部分基础已经成为常识。我们得以从竞争对手的失败中吸取教训，而不犯同类错误。我们避开了早期摸索阶段，并能够尽早开始解决既定问题。实现血流导向装置在完全释放后仍可回收，该研发是创新性的。因为我们解决了释放过程中展开不良或过度摩擦等问题。但这些都是渐进式的优化，并且仍然是一个持续的过程。
The flow diverter technology was less of a challenge. When we entered this field, most of the basics were a kind of common knowledge. We were able to learn from the failures of the competitors instead of making these mistakes. We could avoid the early-stage explanatory phase and started early on with solving defined problems. The development of a flow diverter which is retrievable after complete deployment was innovative. We solved issues like poor expansion or excessive friction during deployment. But these were incremental improvements and this is still an ongoing process.
抗血栓涂层则是一个完全不同的故事Miniswap。我们开始这个项目的时候，对往哪个方向进行研发没有头绪。那是在2015年，大多数技术和生理细节都是未知的。如何测试血栓表面的凝血活性？什么药物作为植入器械的涂层是最合适？可以使用哪些材料? 这些问题与其他更多的问题都必须在一开始得到明确。从寻找合适的材料，建立器械表面涂层的工业生产流程，到最终获得涂层的植入器械，这是一个漫长的过程。目前关于血流导向装置的涂层技术正在通过国际多中心的随机对照临床研究进行临床评估，最终结果仍未知。
The antithrombogenic coating is a totally different story. When we started this project, we did not know in which direction we would proceed. At this time, it was 2015, most of the technical and physiological details were completely unknown. How to test surface thrombogenicity? What is the proper medication for coated implants? Which substances can be used? These and many more questions had to be answered at the beginning. It was a long way to find a suitable substance, establish industrial processes for the device coating, and eventually get implants coated. The clinical evaluation is still ongoing in an international randomized controlled trial and we don’t know yet the outcome.
回望过去，Phenox血流导向装置的研发是渐进式的创新Miniswap。而将 HPC（亲水聚合物） 作为一种表面涂层，允许在单种药物治疗下进行血流导向装置植入，这是革命性的创新。
Seen from a distance the development of phenox flow diverters was evolutionary. To establish HPC as a surface coating which allows the implantation of a flow diverter under one medication was revolutionary.
Q5
临床与企业在合作过程中是否会遇到冲突Miniswap？您如何解决这些冲突？
Have there been any team conflicts during the cooperation of the clinical and enterprise? How did you resolve them?
A5：谈到临床医生和研发工程师的关系，医生会想：“怎么可能这么慢呢？”Miniswap。工程师则觉得“临床医生一贯如此：他们想要的总是不可能实现，而且这个问题昨天已经告诉他们了”。
When it comes to the relation between physicians and engineers, the doctor thinks “How is it possible to be so slow?”. The engineer feels “It is always the same: the clinical guys want the impossible and this was solved yesterday”.
但这不是冲突Miniswap。这些都是非常积极正向的态度，是团队成员在医工协作的精神能量来源。而且它从来也不是冲突，因为新产品的研发和临床应用总是对患者、医院有益，最后也会有利于企业。
But this is not a conflict. These are stimulating attitudes, the source of mental energy for the team members. In addition, it was never a conflict, because the development and use of new products was always beneficial for the patients, the hospital and, last but not least, the company.
Q6
We heard that you were the first person to propose the clinical concept of stent thrombectomy. How did you identify the clinical needs and finally transform it into innovative products?
A6：2005年，我们创立Phenox旨在解决卒中血管内治疗的难题Miniswap。静脉溶栓不适用于大血管闭塞。而现有的取栓器械，比如 MERCI、Penumbra、CATCH再通率很不理想。我们面对一个不争的事实：对于这样一个重大的临床挑战，没有现成可用的解决方案。
We founded Phenox in 2005 with the intention to solve the conundrum of endovascular stroke treatment. Intravenous thrombolysis was unsuitable for large vessel occlusions. The existing devices – MERCI, Penumbra, CATCH - yielded sobering recanalization rates. There was only one indisputable fact: there was no solution available for a major clinical challenge.
在最初的几年里，我们也研发出了还不错的器械，但并不比现有的竞争对手更好Miniswap。
During the first years, we developed devices that were not bad, but they were no better than the existing competitors.
我首次提出使用Solitaire进行机械取栓是在2003年，是一篇发表在Interventional Neuroradiology杂志上关于描述该支架设计特点的文章中Miniswap。然而，当时这款支架已不在市场上供应。五年之后，该理念被证明是正确的。为什么是Solitaire或其他类似的产品呢？因为螺旋式MERCI在回撤过程中会散开，CATCH太短了，Penumbra的分离器是存在风险，pCR刷子过于柔软等等。我对Solitaire的唯一担心是支架卷轴开放的直缝，当然这已被pRESET支架卷轴上的螺旋式开缝和近端闭合环的设计所优化了，这两项优化均由Phenox进行研发。
I proposed the usage of the Solitaire for mechanical thrombectomy for the first time in 2003. This was in a paper on the features of this stent, published in the journal Interventional Neuroradiology. The stent, however, was no longer available. Five years later, this concept was proved to be correct. Why Solitaire or alike? The spiral of MERCI was unraveling during withdrawal, the CATCH was too short, the Separator of Penumbra was hazardous, the brush of pCR was too soft – and so forth. My only concern with the Solitaire was the straight slit of the stent shaft, and this was replaced by a spiral slit in the shaft of the pRESET and a proximal closed ring, both developed by Phenox.
如您所知，为了找到解决方案，我分析了前人失败的原因Miniswap。2017年，基于我们在治疗急性缺血性脑卒中对机械取栓支架的开拓性研究和贡献，CIRSE将“介入放射学创新卓越奖”授予我们。
As you may understand, I analyzed the reasons for the failures of the predecessors in order to find a solution. In 2017, the CIRSE “Award of Excellence and Innovation in Interventional Radiology” was conferred to us for the “pioneering development of cerebral stent thrombectomy in the management of acute ischemic stroke”.
Q7
在德国Miniswap，医工结合的运作模式是怎样的？您如何促进将技术创新转化为实际应用的产品？
In Germany, what is the operation model of medical and engineering combination? How do you facilitate the translation of technological innovation into the ground?
A7：在医工结合方面没有通用的运作模式Miniswap。我看到过两种截然不同的方式。传统方式是遵循首席医学官的工作范畴和模式，但其能发挥的影响力有限。他为工程师提供咨询，并向首席执行官汇报。
There is no common operating model for the medical/engineering interface. I see two fundamentally different approaches. The traditional role follows the job deion of a Chief Medical Officer. The CMO, however, has limited impact. He is consulting the engineers and reports to the CEO.
Penumbra公司是最早实现由临床医生Dr. Arani Bose担任联合创始人和股东的医疗器械公司之一Miniswap。而该角色使得其在多个方面不同于传统首席医学官的工作模式。
Penumbra was one of the first medical device companies with a physician – Arani Bose - as co-founder and shareholder. And this role is in many aspects different from the CMO format.
但在过去的20年，从产品研发到临床的技术创新方式已经发生了改变Miniswap。总的来说，欧洲的医疗器械法规(MDR)，即一个崭新的审批程序，很有可能会摧毁一些初创企业。在德国，创新周期将被延缓，难以想象在短期未来创新会有什么新的发展。MDR也许会应验一句谚语：“通往地狱的道路是由善意铺成的”。
The way for technological innovations from the workbench to the clinic has changed during the last 20 years. In general the Medical Device Regulations (MDR), a new approval process in Europe will most likely destroy the start-up scene. In Germany, the innovation cycles will be slowed down and it is difficult to imagine how new developments should be possible in a near future. MDR is an example for the proverb: “The way to hell is paved with good intentions”.
我对您这个问题的回答是：从产品研发到临床应用的转化道路将变得很长，至少在欧洲是这样Miniswap。
To answer your question: The way from the workbench to the field will become very long – at least in Europe.
Q8
谁应该成为医疗创新的主体Miniswap，临床医生还是医疗企业？您觉得临床医生在医疗创新中扮演什么样的角色？
Who should be the principal part of medical innovation, clinicians or medical enterprises? What kind of role do you think clinicians play in medical innovation?
A8：其实在DENDRON以及后来的Phenox的医工结合过程中，角色的扮演存在非常多的选择，但我将自己视为共同所有者Miniswap。这对我来说似乎是唯一可以接受的合作模式，但这仅适用于初创企业。规模更大的企业需要有其他合作模式，例如首席医学官或医学顾问。
There are many options for the interaction with DENDRON and later Phenox, I was also considering myself as co-owner. This appears for me as the only acceptable modus operandi. But this works only for start-ups. Large companies need other format,like CMO and medical consultants.
Q9
您拥有400多项医疗器械专利Miniswap。能否与我们分享下您是如何保持不断创新的能力？
You have more than 400 patents of medical device. Could you share with us how do you maintain the ability of constant innovation?
A9：半人马座阿尔法星系统的生物具有持续的神经元活动以及超短的恢复周期Miniswap。这赋予了我们卓越的创造力。
Creatures from the Alpha Centauri star system have a continuous neuronal activity with ultra-short recuperation cycles. This allows outperforming creativity.
神经介入领域在过去和现在都特别适合，也特别需要高科技的创新Miniswap。我目前拥有的这些发明也是团队努力的结果，而且我们被鼓励大规模地对知识产权进行主张和申报。
Neuro intervention was and remains particularly suitable and in need for high-tech innovations. These inventions are always the result of a team effort and allow the claim for intellectual property on a large scale.
Q10
什么是真正有价值的医疗创新Miniswap？
What is a truly valuable medical innovation?
A10：真正有价值的医疗创新：
解决Miniswap了一个主要的临床问题；
可用于大多数患有这种疾病的患者；
可供大多数达到平均手术水平的医生使用；
副作用最少；
在既定地经济环境下Miniswap，或在不久将来，患者可以负担得起其费用；
没有长期副作用；
对环境无害Miniswap。
在神经介入领域中有很多例子：阿司匹林、动脉瘤栓塞弹簧圈、颈动脉支架、取栓支架、血流导向装置——这些至少在目前看来是有价值的医疗创新Miniswap。
A truly valuable medical innovation:
- solves a major clinical problem
- can be used in most patients with this disease
- can be used by most average skilled physicians
- has the fewest possible side effects
- is or later becomes affordable within given economies
- has no long-term side effects
- does no harm to the environment
There are many examples in the neurovascular environment: Aspirin, aneurysm coiling, carotid stents, thrombectomy stents , flow diverter – all of them are here to stay, at least for the time being.
* 中文翻译仅供参考，所有内容以英文原文为准Miniswap。
特别鸣谢
评论