In the new installment of our podcast, Dr Joe Lennerz, the CSO of BostonGene and a long-term lecturer of the Advanced Oncology study program, is talking about teaching pathology to the Advanced Oncology students and about one of the initiatives he co-founded with Dr. Ester Abels and Dr. Brandon Gallas, the Pathology Innovation Collaborative Community, now hosted by the Medical Device Innovation Consortium 

Tune in to learn about obstacles in the implementation of innovations and how to overcome them. As a board-certified pathologist, Dr Lennerz is familiar with reluctance towards innovation and change but – in the end – also with the benefits that implemented change will bring to the patients. Dr Lennerz often points out: The precompetitive space is the place where real magic happens. Collaboration in the pre-competitive space has the advantage of being able to gather critical evidence and arguments that will ultimately be part of a jointly acceptable solution.

The Data for Health Initiative of the German Ministry of Health is another project Dr Lennerz is involved in, and lots of magic is happening there as well under the leadership of Dr. Susanne Ozegowski.

Transcript of the interview:

USS: [00:00:00] Welcome to Caring and Sharing - the Advanced Oncology Podcast. My name is Uta Schmidt-Strassburger. I am meeting Jochen Lennerz today. Joe, as he goes by in the U.S., is currently the Chief Scientific Officer of BostonGene. Until last year, he served as Medical Director in the Massachusetts General Hospital’s Center for Integrated Diagnostics. He taught also pathology at Harvard Medical School. He is currently the president of the Association of Directors of Anatomic and Surgical Pathology. Also, he is a member of the Federal Advisory Committee of the CMS, where he also serves as a co-chair. On top of that, he is connected with the German Ministry of Health as the co-organizer of the Data for Health Initiative (#dfh). It's really a pleasure to see you. Welcome.

JKML: [00:01:04] Thanks for having me.

USS: [00:01:05] You insisted that I explain how we met. I did not point out in the introduction that you are also among the lecturers of our study program. Not only are you sharing your insight into the molecular biology of several diseases, but you are also serving and have been doing so as a lecturer in our very first attendance seminar. This is the one where we do explain, or we try to convey and level up the knowledge of everyone who's participating to a certain level if it comes to classical anatomical pathology, but also where you give an introduction into molecular diagnostics. And I think you really relish in doing that job. You have never, ever declined to do that because you seemingly enjoy it.

JKML: [00:02:05] First of all, I really love working with you and the entire team. But what I really think is amazing in this master course, is that people who join are very enthusiastic about what they do, and they come from different backgrounds. So, the seemingly daunting task to get everyone up to speed from traditional pathology all the way to molecular diagnostics or precision oncology, I think, is a challenge. But it's also always super fun to get bombarded with questions from all different angles and of course, big shout out to all the various teams that suffered through those hours of pathology. But I really enjoy the group and, of course, the teams - it's all about the people. So, thank you.

USS: [00:02:52] Thank you for doing all this amazing work. What I like best is that usually the people, when they see six hours of pathology or even more than six hours of pathology, they start groaning. But in the end, they would love to have so much more. Usually the final say is, well, we are so unhappy that it's already over. And I think that's, a great thing because it means you did an amazing job. They are invested in the entire program, in the entire process. I couldn't think of a better person doing that than you.

JKML: [00:03:30] Thank you. Well, I believe pathology, you can see it as what's portrayed on TV with autopsies and weird people, but you can also just enjoy the total broad spectrum of diseases because it is really the study of diseases. If you're a good physician, a good oncologist, you in a way have to understand the diseases. And I think just the topic or the name maybe is not the most attractive. But, you know, everyone uses laboratories, everyone uses lab medicine and uses a lot of different insights into diseases. And I think that's where I get very fascinated by how clinical the field is. And maybe, maybe that helps. But I also always enjoy talking six hours, just pathology. That's fantastic. And making it as interactive as possible. And thank you again for allowing me to do this over the many years.

USS: [00:04:29] It's always a pleasure to have you.

Today, we agreed to talk about the – and it says it already in the background of your screen – the Pathology Innovation collaborative community. What I would like to know on behalf of our listeners is first, how did the whole thing come about?

JKML: [00:04:54] Thank you. First of all, the two first words, pathology and innovation may seem already a little bit contradictory because pathology is one of the oldest disciplines in medicine. And then coupling that with innovation is already sort of a weird thing.

The story of how I came about doing this is actually very, very fascinating because one of the oldest and probably most powerful tools in medicine is the microscope. Back in Ulm, I was working on a type of research called digital pathology. When I switched back over to Boston at Mass[achusetts] General [Hospital], I continued to do so, and I do so in my current job as well. That is basically trying to digitize histologic slides using a microscope, but a digital microscope, and then you have access to that data. Now that sounds like it should have been done in the 80s, but it hasn't. It is for various reasons, and we can talk about this. But the story began when we decided that jointly with, in that case, an industry partner - and back in the day that was Philips, but there are many other companies now that that have achieved something similar, which is that we said – we really want to take a slide scanning system to the FDA and push that through in terms of an instrument precision study. During that time, I was at first completely ignorant, like, why? What's needed? I mean, it's a slide scanner, [00:06:25] it will scan an image, you look at it, it makes sense. And I was slowly but promptly introduced to the topic of regulatory science by one of my good friends and colleagues, um, Esther Abels, and she at the time worked with and for that company, and we kind of jointly planned this out. I turned out to be the principal investigator of that study, and that ultimately led to an FDA approval of the first digital whole slide scanning system.

And then fast forward a few years later, this did unlock some parts, but not all parts of digitization and pathology. And jointly with a colleague in the FDA, Brandon Gallas, we sat together and brainstormed how we could help unlock some of the potential in this field. And those three people, so Esther, Brandon and myself then, are the founders of what's now called a Pathology Innovation collaborative community. But there's like a few more steps than that. But that's sort of the quick thing, how I came to it. So basically, as a naive researcher who wanted to put something in clinical practice which you could consider innovation. So: It's all back to the microscope.

USS: [00:07:45] It is amazing what you've achieved so far. And I think you gathered quite the nice community. What I shall say is that you are meeting on a regular basis every [last] Wednesday [of the month] at, I think it's 3:00 Eastern time, it's in a completely open meeting so you can check the website out, but you're also present at YouTube. And I think that's really amazing that there is so much transparency about what's going on. So, it's not something that you do behind closed doors, but you're quite open about everything that you strive for. And I think this permits a level of engagement from both the scientific community, if they were interested in it, but also from the general public, because in the end, whatever you're doing, you're doing that for the general public, for the benefit of everyone. Of course, it is important that it's being seen and it's being heard and that those decisions are being made in a cooperative manner. I really like that.

But I could imagine that there are quite a few people who are not so happy about the digitized part of pathology. How do you deal with that?

JKML: [00:09:06] Fantastic points. Maybe I start, with the community part and then we go into the “some of the people who do not like digital so much or digitization or digital pathology”.

First, the community is literally community-driven, and I'm always trying to engage multiple people in the projects. It's not just the same small group of people leading it, but I'm very thankful that the Medical Device Innovation Consortium, which is our official convener of the community, is helping and supporting us. But as you pointed out, it's really open to everyone: private people can come, patients, patient advocacy, industry, academia, healthcare providers, whoever can join and raise topics or propose projects and those are all on the website.

And the community is merely a platform for people to discuss various things. And that, I believe, has not been tried like that. So, we are literally recording everything. Sometimes we need to do a little bit of monitoring, and I want to, maybe in a bit, explain why. This is not a place for people to feature their products. And I just want to be clear about that. And that's not the purpose. The purpose is really to tackle common problems. While it sounds a bit strange that, well, everything is digital nowadays, why can't histologic slides be digital? Well, they can be, but can they be in all settings for everyone all the time? And that raises very interesting questions. For example, who would pay for this? Because, you know, I need digitization technology, while it has some obvious and some not so obvious advantages, has to be covered in terms of cost to be financially sustainable.

[00:10:55] So, that's some of the questions we talk about.

Now to the second part of your question. Why do some people not like digital pathology? There's many, many reasons for that, but I just want to first give you a quick glimpse into, you know, those little slides that many of you know from high school or from a laboratory session back in gymnasium? When you look at that, it's a couple of cells and it looks beautiful. And there are those pictures in the textbook. But when you look at it from a higher resolution scanning perspective, and now we get a little technical, the amount of data that you can capture on a single slide is probably on the order of 10 to 30 times a full body MRI. So that is a whole-body MRI scan you could fit in terms of like individual images at the current high resolution on a 10th of a regular histologic slide. So, in other words, if you have an average breast cancer or colon cancer or lung cancer case, let's say a resection of a lung with resection margins and the tumor cells and the lymph nodes sectioned and then scanned. This is a data set that is in the three-digit gigabyte range. It is extremely hard to manage this type and size of data.

Now: Do you need high resolution for every single slide? If there is a benign lymph node that you can see at low power magnification, you may not need for the Xth scanning. But if there is cancer, you might want to look for the cells. So, this level of flexibility in terms of the data versus ability of the microscope, where you just say, oh, here I want to go to 40 x costs us currently nothing computational. It can be done by the pathologist when looking through it and just changing the power. But once, when you want this digital, either the technology has to become so good that you have that always at high power or not. That's one example of about 50 that we identified. Data standardization is another, workflows, modularity, interoperability, the heterogeneity of scanning the downstream algorithms that you can run on these images.

Some people, when confronted with a technological revolution of this magnitude, that basically changes practice – and that gets a little bit into change management, which I know you're a big fan of – I just confronted with something that is just too much when putting their name on the bottom of a report every day for whether someone does or does not have cancer, which is arguably one of the biggest decisions that any medical doctor ever makes. And before engaging in a technological plethora of problems, some people just revert and say, I wait for another year, I wait for another two years, and I love my microscope – and I still do – and when I do my day-to-day job, I much rather rely on the technology that's been proven over decades because I'm putting my life and my professional career on it.

I don't know if that's adequate for everyone who's against digital pathology, but that's some of the recognizable reasons that are heard. I don't know if that answers the question, but just as a brief outline.

USS: [00:14:22] It makes perfect sense in the order of the magnitude that you explained it.

I think we provided already quite a few things that I would like to line out in today's podcast: One would be the link to your website, which we will apparently post also on the professional communication platform [LinkedIn].

Is there anything new and exciting that you would like to share with our listeners concerning the pathology innovation, Collaborative community?

JKML: [00:14:54] So maybe just quickly, the term collaborative community sounds a bit like a couple of hippies sitting around in a circle, dancing, but it is actually a fairly rigorous review process because the FDA, who is one of our participants, has specific rules to engage with the community. I don't know if you've ever been in an FDA meeting to just quickly say, and that's the same on the European and the Japanese side, with any regulator. Typically, it is a fairly confined and confidential space where you propose something and they make comments or revise, and the knowledge gained from within those confidentiality-bound sessions usually resides within that group. In other words, if company X has a proposal and then company Y comes, it's not easy to share some of the knowledge that's derived from these interactions. In the collaborative community, the interesting thing is that the regulators can join and speak on behalf of themselves, and it is a pre-competitive activity. Now, that word pre-competitive is probably the coolest new thing, and it's not a new thing, but I just want to emphasize it because the Pathology Innovation Collaborative community harnesses this pre-competitive space.

Some of the accomplishments in the pre-competitive space have changed our lives. I give you a few examples.

A USB stick that was a development made in the pre-competitive space where a few people got together. And to some of the older listeners, you remember this. It was a different plug and a port for your printer versus your mouse versus your keyboard versus, you know, all your other, you know, peripherals of a computer system. And they jointly said “That is costing us a lot. Why don't we use one - sort of - more harmonized, more interoperable way” and then, you know, USB-B, USB-C happened. Now that's an example for an accomplishment in the real world for activities in the pre-competitive space. Dimensions connectors were developed and then the specifications were set. And then people could go in the competitive space and build products around it.

Now. other tools that were developed in the pre-competitive space are Wi-Fi, Bluetooth. These are data standards and exchange mechanisms that have, I believe, really changed our lives. So, as this collaborative community acts in a pre-competitive space, we can jointly tackle problems that people bring in very different perspectives. You know, some scientists from a university come and say, we have written this paper and they share plenty of papers that we briefly discuss. But then from industry, the point of view is more how can we leverage this to make our products better? From a patient perspective, there's like “look, we have a dire need to help patients with deadly or rare diseases”. How can this technology, maybe, help bundle data from rare diseases, interoperable fashion to get data together for sharing?

And then, of course, the most or the arguably most important aspect is how can this inform the regulator on how to help us make these products risk-averse and safe, but at the same time not really just hinder innovation? So that sounds like a very complex space to act in. And some people sometimes feature their products, but that's not the place.

In the pre-competitive space, you really just try to tackle new things, 2 or 3 elements that just to give you concrete examples that are really very cutting edge and there's no predefined regulatory solution, is, for example, machine learning and artificial intelligence can leverage the data once they're there. And of course, as you move forward in time, the more data you accumulate, it might be important to use the additional data to improve your algorithms. Now, as humans, we do this all the time. Actually, we can't fight it. The more exposure we get over life, we call that experience and then we act in a more experienced fashion.

Or when it comes to a machine learning model, it is very hard to say “Well, what is a performance metric of a machine learning model when it gets retrained as data come in?” And this is called online learning or relearning or live models, people have different words, for it is one of the biggest regulatory hurdles because if the model is changing the performance changes, then you never really know how good or bad the performance is. So, you need to come up with things around that. The regulatory time for that is predetermined change control protocol or PCCP. That's one of the methods that we do.

Another very exciting topic is a cyber security. Just to have data of this magnitude about cancer or not cancer on file gives us new abilities. For example, cancer versus no, cancer is not a black and white decision. Every pathologist knows that. But to lay people, it seems “Is this cancer now or not?” And in some cases, it is really hard to define. Having this data available in digital fashion might enable more quantitative expression of things. To give a concrete example: one of the most innovative therapies for breast cancer targets a molecule called Her2, and only recently became clear that low expression of Her2 can actually be targeted. That's a quantitative measure that everyone is not talking about, how to identify it more reliably. And some of these topics I just quickly outlined are things that we discuss in the PIcc group.

USS: [00:20:43] This cuts into a topic of a thesis that I'm currently co-supervising about low Her2 two levels and how they are being assessed.

JKML: [00:20:53] Maybe just one quick anecdote.

When we started the Her2 low project and a lot of people were interested in it, we said so one of the meeting themes was what should we focus on? Is it the evaluation part, the procedural part, the essay? And in the end, we collected something like 22 topics that touch on every single aspect of testing. It was basically an overview over the entire workflow that is all relevant just because one immune-stain can be evaluated slightly differently, which says a lot about the complexity of pathology. But no, but I'd love to. I love to see the thesis.

USS: [00:21:33] I have the graphic in mind that's on the website and it's really great work.

JKML: [00:21:39] Thank you.

USS: [00:21:39] So thanks a lot for joining me today. And I hope that our listeners could find something useful.

If you liked this podcast, please like and subscribe. See you next time. Bye bye.

JKML: [00:21:54] Thank you.