Part two of a two-part interview. For part one, see CBA News 7/4/05.
Ivan C. Baines
Scientific Coordinator, Director of Services and Facilities
Max Planck Institute of Molecular Cell Biology and Genetics
At A Glance
Name: Ivan C. Baines
Position: Scientific Coordinator, Director of Services and Facilities, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany, since 1999.
Background: Director of business development at Cenix BioScience, Dresden, Germany, 2002-2003
The Max Planck Institute of Molecular Cell Biology and Genetics serves as the hub of perhaps the largest industry-academic collaborations in the field of high-content screening for drug discovery: It is the coordinating institute in the High-Throughput Technology Development Studio project, a collaboration that is funded by the German government through the BioMeT Network and includes the Technische Universität Dresden; HCS vendor Evotec Technologies; image-analysis software provider Definiens; and RNAi firm Cenix.
In the first installment (see CBA News, 7/4/05) of this two-part interview with CBA News, Baines discussed the beginnings of the collaboration, why MPI-CBG works with the vendors it does, and the importance of flexibility when it comes to working with HCS vendors.
In this issue, Baines talks about MPI-CBG's software and RNAi collaborators, how technologies from the participants complement one another, and bringing pharma on board.
So regarding the other parts of the collaboration …
We also realized that an extremely critical part of the whole constellation was the ability to perform image analysis on the output. And we knew that this had been a real struggle in this area, and there were quite a few products that were useful for particular things, but they did not match, or even come close, to doing what we were interested in doing. In fact, there is sort of an amusing way that this came about. The head of our microscopy facility, Kurt Anderson, was at a trade fair in Munich and he saw a booth that was showing image analysis on continuous gray-scale aerial photography.
The Definiens platform?
Yes, and Kurt saw this, and asked them if they had thought of applying this technology to micrographs, and that's sort of where that started. They said that they had been thinking about it and were interested, so we starting applying their so-called object-oriented recognition principles to our microscope images. And we were very excited about this, because it was completely different. We had a couple of tests: One was distinguishing gold particles from ribosomes in electron microscopes, which had been a long-term problem. You're not distinguishing objects from background noise; you're distinguishing objects from like objects. That's the critical thing. Often you have vesicles that look like mitochondria … different things in the cell look like one another, so you need a way to distinguish that. And again, we've been absolutely delighted with that collaboration, and have been working very closely with them for a few years, through a couple of different transitions within their company.
This is used primarily with the Evotec instrument?
Yes. But we use [Definiens'] Cellenger on images taken with other microscopes, too. But we do the on-line [image-analysis] applications solely with the Opera.
Is the Opera a better platform when the Definiens software is used with it?
We feel the Cellenger is a lot more powerful than the Acapella, the [Opera] image-analysis software. We like Acapella because it's quick and simple, and in certain cases, when you don't need the functionality of Cellenger, it's a better tool for on-line automated analysis, when you need to actually analyze the images in parallel with the screen, rather than subsequently. If you do it offline afterwards, the deeper functionality and slightly slower analysis of Cellenger is not an issue. But on particular cases, when you're running a high-throughput screen, you may want Acapella.
And how did Cenix end up in the fold?
Cenix was a spin-out of the Max Plank institute, from the labs interested in RNAi — specifically, Tony Hyman's lab. Anything where we're doing RNAi at a larger scale, we work backward and forward with them — we would have to do the proof-of-principle, more of the basic research, and they tend to do the applications at a larger scale. This is also a far more integrated collaboration. For example, there was a recent publication in Nature [2005 Jul 7; 436(7047): 78-86] dealing with the analysis of kinases during endocytosis, and Cenix did the analysis on the first set of kinases, and then we did the secondary screen.
The Max Planck Institute is still a customer, correct? It is actually buying the platforms from these companies?
Actually, Evotec and Definiens, and to a more limited extent Cenix, have credited the promotion and exposure that we've provided with a significant impact on their sales. I think that all the partners have a high degree of enthusiasm. Our institute is a little bit unusual in the way it goes about industry collaborations — it also adopts the agenda of the industrial collaborator. We believe that we have to continually feed the collaboration with a means of generating enthusiasm. The magic ingredient for the success of a collaboration is not necessarily money. It's also enthusiasm, and what level of commitment and effort both partners put into it. In order for a company to put in a lot of enthusiasm, it has to see an immediate financial benefit, so we're very interested in helping provide that, obviously within the constraints of being a public organization. Also, we're not just applying the technologies to meet esoteric basic research questions at Max Planck. Instead, we're asking a question that we think is essential in pharma, biotech, and life sciences. We're asking a more general question, which I then think becomes more valuable to an industrial collaborator, because it addresses their entire market segment, rather than a particular opportunity.
We also agree to perform a certain number of demonstrations, and in certain cases we formalize that in terms of what our productivity has to be in terms of publications, exposure, demonstrations, beta testing, feedback, technology refinement, co-participation in conferences, and so on.
This is a rather unique industry-academic collaboration, especially when considering the scope of the players involved …
There are other collaborations with academia, but typically each company does have a single major collaborator. Here we've got collaborations in all areas; in other words, we've sort of built a jigsaw puzzle, and it's through intention rather than coincidence. It's been very interesting to facilitate the discussions between the particular companies.
Being that all the companies involved in this collaboration are from Germany, this would seem to also be beneficial to the German biotech industry as a whole.
That's a very good point, because we were selecting our collaborations at the same time as preparing a grant application. One didn't require the other, and in fact, with regards to Evotec and Definiens, the fact that they were German didn't, in fact, help us, because the mechanism of the grant was actually specific to the new German states, which Max Planck, being in Dresden, satisfied, but Definiens coming from Munich and Evotec coming from Hamburg, did not. But Evotec, in fact, does have a subsidiary in the East part of Berlin, so it can satisfy the requirement, and Cenix, of course, is in Dresden, so it does as well. But this was definitely a mechanism that was definitely supposed to be enhancing economic development in the new German states, as well as scientific progress.
Your colleague Eberhard Krausz also mentioned a 'pilot study' you did with Ambion …
Ambion we like very much, and they have a long-term relationship with Cenix Bioscience. Cenix has designed the siRNA reagents that compose the libraries of Ambion. They've been working together for quite some time. Ambion is very much focused on the research market, and has sort of made a point of maintaining quality standards in its reagents, which we wanted. And in fact, I think there was a press release from Ambion about the [aforementioned] Nature paper, because their library was used. And we are in a consortium with the EMBL working on the application of genome-scale screening in the area of cell division, and we're both working with the Ambion library.
Looking ahead, what are some of the overall goals of this collaboration?
I think now no one questions the value of cell-based analysis or genome-scale RNAi screens. There is still a lot of ambivalence in the pharma sector as to whether or not cell-based screening will be useful for drug discovery. What will change that? The only thing that will change that is when it's been demonstrated that a cell-based screen results in a higher success rate in the clinic. That's an 8-to-12-year experiment, which is hard. We have an idea of a shortcut. We have two main missions: to demonstrate that cell-based screening does result in a higher success rate in the clinic, but we don't want to wait 12 years; so we're designing experiments to demonstrate that, so we have a means of reading the clinical success of compounds on the basis of their performance in these early-stage discovery assays. We're designing experiments along those lines, and that's a more general question.
A more focused investigation is our application of what we consider to be very sophisticated multi-parametric assays in a limited number of disease areas to specifically evaluate how it performs in the context of a particular indication. We've chosen three diseases and somewhat unusual targets and assays — though recently well-validated in terms of disease relevance. Currently the areas are infectious disease, diabetes, and cancer. But I should say that it's not so much that we try to cover a particular disease; it's more about where we have a particular unique insight into the disease, where we have a particular set of assays or a handle on something.
Will you be collaborating with pharma on this?
Yes, we will. We've been visited by more or less all of them, and there's a lot of interest. Since we don't need money, because we're well-funded by grants, we're interested instead in designing an experiment which sets some goalposts that we would in the future both be interested in. So there is quite a lot of enthusiasm, but we only wish to establish those partnerships between now and the end of this year, because then we have a six-month to one-year prospect still working within a number of our major grants.
Are there plans to incorporate other collaborators, such as reagent providers?
We continue to be open, and more collaborations are on our radar screen. I would say the next most significant collaborations will be with pharma in particular areas.