Rudi Balling: I am representing, I think, one of the greatest
countries, but probably the smallest today.
[laughter]
And I am actually very thankful to Geoff for not distributing the time to talk here according
to the size of the population.
If we calculated it through, it would give us, Luxemburg, 1.5 seconds to talk.
Now, this is where Luxemburg is, so it's 80 kilometers North-South and 60 kilometers East-West.
And it has 500,000 people, five hospitals, five research centers, and we have a budget
of about €5 million per year to do genomic science, medicine, systems biomedicine.
I think in terms of the context it is important to know that 10 years ago, the country did
not have a University.
It was established in 2003.
And all the young and bright students that wanted and could go to a university were actually
very proud of being able to go and get scholarships to go to Brussels, or Vienna, or U.S., or
ever.
And it's almost a culture of the country to say we need to send our young people out so
they come back and they have seen the rest of the world.
So there was a lot of resistance to build the university.
And the resistance came from the academics.
Ten years later the game has changed.
The country, I think, is becoming proud of the University.
And so there was a decision made to put -- make it research oriented.
And about five years ago there was another decision made, namely, to set priorities and
to focus because in a small country, in a small university, you can't do everything.
And one of the priorities, the other one is telecommunication, security, reliability,
and trust.
There are some banks in Luxemburg.
The other one basically was to go for biomedicine.
And if you just -- how do I move this forward -- the right one.
The rationale was that Luxemburg has undergone a couple of [unintelligible] cycles in their
economic development.
A hundred years ago it was basically an agricultural country, with some wine at the Mosel.
And then, about 150 years, 100 years ago, steel industry came up, which in the '70s,
1970 reached its peak with more than 40,000 people working there, out of 250,000 people
at the time.
That went into decline -- with still 5,000 people working in the steel industry, and
the banking business came up.
There were more than 250, 280 banks.
I think there are still 150 to 180, which serves the country well.
But things change, and now this is what happened in 2005.
The decision was made to basically re-build the entire steel industry down -- this is
the steel campus, these are still the furnaces here that are now mall monuments -- to transform
it into a city of a university and business.
And this is where things go, and there was an investment of basically, in dollars, of
about $200 million.
This is probably about the biggest construction site currently in Europe.
And this is where I work, right here.
This is a bank.
And those are student houses and private houses.
This is the main building of the university.
And this is the humanities building, and the mathematics building coming up, and so on
and so forth.
So if you come over and visit, it's worth taking a look at it.
Now, there was a question about vision in terms of genomic medicine and personalized
medicine.
I think one of the visions and the scarce is that there needs to be another future in
terms of economy.
That's why I was sort of a little bit sensitive about the question that my Belgium colleague
asked.
Let's keep business out.
In terms of the expectations, there is an expectation that health, health insurance,
wellness, is not the only a cost factor, but maybe also a business opportunity.
Now that's not the only incentive in Luxemburg to build biomedicine and personalized medicine,
but it's one.
And I think it's important, at least for me and the expectations that are built into our
institute.
It's in this context of, what do you give back in terms of economic?
You can be saving money but can also be attracting business.
So, there are always two coins of this.
So, I was charged in 2009 as the founding director of the LCSB, Luxembourg Center for
Systems Biomedicine.
The name that had been given to me was "systems biology," and in four weeks, I changed it,
I said "I want to work in systems biomedicine."
And it served us well, that decision.
And the concept is basically not unique, it's what I think every center in this time of
age does, is combined experimental biology with technology platforms.
Make a big -- that's why it's red here -- make a big focus on computational biology, and
then reach out to clinical research and clinical implementation.
Now the reason why I point this out is when you have 500,000 people in a country, you
cannot compete in being a role model in terms of large number of patients.
You have to have a different unique selling point or a competitive advantage where you
can contribute to the international community.
So don't expect from Luxemburg big cohorts.
You might expect a pilot, small and beautiful, because Luxemburg has only one health insurance.
I come from Germany originally, 35, a zoo, competing and hating each other.
So that is a very different context.
And I think there is a big chance in Luxemburg here.
Now, I had to make a focus, and a focus in terms of a disease.
So we can't cover all of the diseases, although most of the diseases occur in Luxemburg.
I made a choice and I went for neurodegenerative disease.
Within neurodegenerative diseases I went for Parkinson, not for Alzheimer, although there
was some frantic pressure for me to go into Alzheimer from the political side.
I resisted that because I thought the door into understanding neurodegenerative diseases
four years ago in Parkinson with 15 familial genes known, in Alzheimer with only three
at the time, is bigger, and genomic and genetic medicine, I thought I had a better quick start.
And that's what we needed, a quick start, because otherwise the politicians lose patience,
as you know.
So, I'm not going into this at all, except to say that the focus that we currently try
to push and implement is become a strong driver and get on the map in bioinformatics, computational
biology, and systems analysis, which is mainly network science right now.
And I am convinced, we heard this in a couple of talks today, that one of the big challenges
is in making sense out of genetic variation in a non-linear system, extremely complex,
progressing and changing the topology and the dynamics over time.
That's what we are facing with, and I think climate modeling is peanuts compared to what
we are getting into this.
Maybe I shouldn't have said that.
But I think we can learn from them a lot.
So, we started, just as an exercise, to get on the map and create pathway maps initially,
and so this is where we sort of see ourselves right now in Luxemburg.
And the cohort studies -- so a lot of the themes that are discussed today, we need and
want to tackle by international cooperation.
This is where we feel at home, and this is the quick way of validating genetic variation,
and then, of course, you have this back and forth and ying and yang.
And so this is basically -- I show this slide one more time -- this is where I think we
would like to contribute to this international consortium to make sense out of genetic variation.
Be it genome sequencing data, be integration, be it the development of integrative maps,
not just sequencing, but all the other omics clinical data, bioinformation, machine learning
essentially.
So, I am not showing any in-depth here, I just want to say I also had to make a decision
for which technology to go for.
The first decision was not going into sequencing, but invest heavily in sequence analysis.
I did go for one technology, which is metabolomics, headed by Karsten Hiller.
I think in terms of this context here, maybe in the workgroups we discussed this a little
more, we have invested -- and I think we are getting the first fruits from that -- into
in vivo metabolomics.
You are looking for fluxes, not just for metabolite concentrations, using stable isotopes, like
a challenge test, like a glucose challenge test.
I think there is information in there which we should harvest from genetic epidemiology
and cohorts.
We can talk more about this in the coffee, or at the beer, or in the workshop.
We have built up a SNP validation tool.
And I just want to point out that this is just -- we are a couple of European consorts
here on epilepsy because of the bioinformatics.
But our fish facility, we were -- because of this we were able to make a functional
validation of a genetic variation of a family that we sequenced with Dravet [spelled phonetically]
syndrome, a genetic inherited epilepsy.
And so very quickly, within three months, we were able to make that contribution.
And we also built up IPS and have started to build up IPS from patients and so.
I'm not really going into this.
So again, the question is how -- what kind of know-how can we bring in, which I am fully
aware hasn't reached the clinic yet, but I think we are on the way.
So, we went into bioinformatics, recruited Ronald Schneider [spelled phonetically] from
the MBL [spelled phonetically] facility in Heidelberg, who was running some of the bioinformatics
there, and went into pathway analysis and network analysis as some of the focal points,
and start to try now to make dynamic and kinetic models.
This is about electron transfer chain in mitochondria, because that seems to be one of the hallmarks
in Parkinson's disease, probably in others as well.
I think it's very relevant for cancer, Warburg effect and all these issues, and I think it
already brings us into some questions of co-morbidities at the model -- disease model level, and I
come back to this in a minute.
Now they recently, in April this last year, we recruited Enise Teeler [spelled phonetically].
And Enise has done a community-driven effort to make metabolic reconstruction worldwide,
so this is the point I want to make: community-driven worldwide curation and disease model or modeling
efforts to make metabolic reconstructions, and we just published, just a few months ago,
a community effort to develop a Parkinson's disease map in joint cooperation with Hiroaki
Kitano in Tokyo to use almost a Wiki [spelled phonetically] format to basically click in
and use intuitively when you want to find the NIH in Washington, D.C.
So, those are some of the European clients where we work.
They are all bioinformatics, computational, more or less, and now the question, what does
this have to do with genomic medicine?
There is just a grand -- in preparation; I hope we get it, looks good -- to establish
a national center of excellence in research in early diagnosis and stratification of Parkinson's
disease.
And Frank Laud [spelled phonetically], from the FNR, the Fornational [spelled phonetically]
Research, is here, can tell you much more about it.
This is a 12-year commitment in Parkinson's disease research, with an extension probably
into AG [spelled phonetically] and others, from the government side.
I think this is extraordinary, and we have all the players in the country.
I mentioned -- I said there were five research centers, this is including the biobank.
There was a big investment made into the International Integrated Biobank Luxemburg.
More than €60 million going into this, the LCSB, the hospital, and the CRP public research
center, Santé Health Research Center.
And this is happening in the next few years.
So, I think the commitment from the country, in terms of moving this into early diagnosis
and stratification with the hospitals, is a big one, and so I think we are quite privileged,
but of course I can't -- I am not sure I can convey the expectations that are put on us:
rescue the economy, change the healthcare system, and, by the way, bring up good science
into the country.
So I think I stop here.
Those are the groups I'm not going into.
It is an interdisciplinary under one roof that is the key message.
Thank you very much.
[applause]
Geoffrey Ginsburg: Thank you, Rudi.
I'd like to just ask you maybe one question, and I may have my facts wrong.
But, first of all, congratulations on what you've done in 10 years, it's --
Rudi Balling: Four.
Geoffrey Ginsburg: Well, okay, four years --
[laughter]
-- going back to when there was no university.
To what extent do you attribute what you've been able to do with partnerships with other
countries, and I'm thinking specifically of the investment that made with TGEN and Institute
for Systems Biology.
I noticed that you didn't mention them, so I'm just curious as to what role they play.
Rudi Balling: [laughs] Well, yes, I have mentioned them.
They have run out, more or less, but they were absolutely instrumental.
So, just for the people who don't know, there was, I would say, about half of the money
that was in was named "The American Project," which was with three different American partners,
and one of them was the Institute of Systems Biology in Seattle with Lee Hood.
I think that, personally, the most productive one and delivered, very, very well, so I don't
mention the others.
[laugher]
But that's a personal thing.
Things really worked out really well.
We basically -- I sent over seven fellows into these institutions, and they stayed there
for two years and then they came back for three years.
We call this knowledge transfer.
That worked extremely well.
Now, the way European institutions work in collaborations is sometimes a little bit different
compared to this continent.
So, I feel we were very lucky -- not lucky, I shouldn't say that.
But it happened that the increase in funding happened into the recession, and it's good
to invest on a stock market when everything goes down; it gave us a big opportunity.
So the doors, internationally for us, were open everywhere.
We are not heavily collaborating, continuing with Hiroaki Kitano, but also the other that
I didn't mention we are going into imaging, cellular imaging, IPS cells and others.
We do this with the Gladstone Institute, with Steven Finkbeiner, quite a lot.
And immediately realized the challenge is image analysis.
Again, bioinformatics.
All these data.
So, yeah, it was absolutely essential.
Geoffrey Ginsburg: Thanks.
We are at --