Listen to the interview (transcript below)

Glossary of terms

Professor Jan Törnell is Global Director for AstraZeneca Transgenics and Comparative Genomics. In connection with his participation at the PharmaDiscovery 2005 conference in Washington D.C. in May, Professor Törnell was interviewed by the internet-based talk radio programme Science and Society.

Dr David Lemberg hosts Science and Society, a programme that discusses innovative science particularly in biotechnology and related industries. The sound file is has been provided courtesy of Science and Society and is published with their written permission.

Transcript

David Lemberg:Our next guest is professor Jan Törnell, Global Director for AstraZeneca Transgenics and Comparative Genomics. In 1996, professor Törnell was recruited to Astra to build and lead a core unit to generate and analyse transgenic models for the company worldwide. Prior to joining AstraZeneca professor Törnell ran a research group at Gothenburg University. He has had a leading role in building transgenic technology in Scandinavia. At PharmaDiscovery 2005 professor Törnell will chair the session “Pharmacological models for human diseases” and will do a closing presentation on “Increasing predictive power of animal models – what can we do?”. Welcome professor Jan Törnell!

Jan Törnell:Thank you very much David. Thanks for having me on the show today.

David Lemberg:You are welcome, Jan. Thank you so much for being with us so late in the evening in Sweden, I appreciate your time.

Jan Törnell:No problem at all.

David Lemberg:Can we talk about moving discovery research, translational research, to the patients? In the States we call this ‘bench to bed science’.

Jan Törnell:Yes, I think that’s a very good name of it, that is really the aim for very much of the research that we do in the pharmaceutical industry. Translational science, or bench to bed science is extremely important. It is a major challenge for the whole pharmaceutical industry that only about 10 percent of the compounds tested in man will eventually become a new medicine. And we definitely must invest to link our data from discovery research to clinical outcome in patients. I think by doing this, by picking the winners early, it is possible to speed up the generation of new important medicines. And actually to use our resources more efficiently and decrease also the risk of exposing patients to possibly non-safe chemical substances.

David Lemberg:Can you tell us what structures you have in place at AstraZeneca to promote this process from discovery to patient related studies?

Jan Törnell:Yes that is clearly a main priority for us in the company right now. And to try to handle that we have formed a discovery medicine programme which includes both discovery scientists and clinical experts. Here we are co-ordinating activities throughout the company to share experience in areas such as biomarker discovery for understanding mechanisms underlying diseases and also identifying the best possible models where you can test potential medicines. We had in parts of the company quite good experience from this before and we are trying to build on the previous strength that we have within efficient seamless interaction between discovery and development.

David Lemberg:With that, can you say what kinds of skills are required, what are you looking for to build a translational team?

Jan Törnell:There are many kinds of expertise needed in a translational team. Clearly the clinical input is extremely important. We must have clinical expertise that can guide us and identify what disease mechanisms we are studying. And then we need to translate this into the pre-clinical side and therefore we need people like pharmacologists, imaging people but also cell biologists and computer scientists, because it will be different kinds of models that will be used in the translational studies, ranging from in silico models, cell-based models, to optimised in vivo models.

David Lemberg:What do you anticipate as the next breakthrough in this overall area?

Jan Törnell:Currently we have the sequencing of the human genome that was done a couple of years back and this is a fantastic resource that I think will enable the community to understand human disease on a molecular level. I think it is important to realise that this is nothing that will happen over night. It will take some time to understand human disease on a molecular level. But when we have that, it’s a tremendous resource. And I think also we have the DNA sequence of several of the model organisms that we use in research and this will actually give us a chance to translate human disease into model organisms. Great advances have been done in recent years also in the “omics” area such as transcriptomics, proteomics or metabonomics. We have great advances in imaging technology and techniques also for functional analysis of model organisms. I think the next great breakthrough actually will come from combining the knowledge that we got from the sequencing of the human genome, the model organism genomes, with these technologies that can be used for analysing that. If we have the skills to combine all that knowledge, I think that will provide us with the next great breakthrough.

David Lemberg:I am thinking that software here is critically important to understand the data. Is AstraZeneca developing its own in-house computer models or are you partnering with other companies in Europe or in the states?

Jan Törnell:We are doing both. Clearly, powerful internal research remains the hallmark of AstraZeneca’s success. We cannot do everything ourselves and we are always looking for new collaborations. So we are developing some software in-house but we are also collaborating with the academia and biotechs in the software area.

David Lemberg:Can we extend our conversation, can you tell us of features that will lead to a successful project with the end result of discovering novel medicines?

Jan Törnell:I think a project that will be successful in the future will have a range of expertise, that I described before, ranging from clinical scientists to basic scientists. I also think it is vital that the projects are working on very well-validated targets, drug targets, because that will give them the confidence to be persistent and actually generating series of compounds that can be tested in man. I think working on a well-validated target and being persistent in that area has been a key to success and I think it will be in the future as well.

David Lemberg:So target validation really is the critical piece?

Jan Törnell:Target validation is extremely critical. A view from many people is that now since we have the sequence of the human genome, we know the 30 or 35 thousand genes, so basically we have all the targets. The problem is that we don’t know what they do; we don’t know how they are linked to disease. And doing that in a clever way will give us a competitive edge, I am quite sure about that.

David Lemberg:We have got a little less than two minutes less. I am certainly interested in your closing presentation topic “Increasing predictive power of animal models”. Can you give us some of the highlights?

Jan Törnell:I think it is extremely important that we try to understand both the opportunities and limitations of all kinds of models, both animal models, cell based models and computer models. I think what we have done in the past is that many of the models used have been of less predictive value or of variable predictive value I would say. We now have the tools to understand how they can be used and what they can be predictive for. And I think also using transgenic technology, it is actually possible to optimise the models. There clearly are areas where we didn’t have any really good models at all before, such as Alzheimer’s disease for example. That was an extremely difficult area to do research in, just say, five to ten years back because of the lack of cell-based models. It was difficult to get access to human material for natural reasons and there were no animal models at all. With the generation of animal models for Alzheimer’s disease it has opened up a new field and there’s a lot of promising research going on in the pharmaceutical companies and in clinical trials as well, very much based on new models for that disease.

[Additional comment: Alzheimer's is a disease with a large unmet medical need, with serious implications for patients and society. With the help of new animal models for mice, AstraZeneca can now perform better research within this area. Previously these models were too unspecific, and therefore not efficient to use for research in this context.]

David Lemberg:Jan, thank you so much for your time and a terrific conversation today.

Jan Törnell:OK, thank you very much.

David Lemberg:You are welcome. Our guest is professor Jan Törnell, global director at AstraZeneca transgenic genetics and comparative genomics. Stay with us on Science and Society.

Published 10 August 2005