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Q&A: Eurofins' Bruno Poddevin on Deciding When to 'Industrialize' Next-Gen Sequencing


PhotoPoddevin2.jpgName: Bruno Poddevin
Age: 47
Position: Senior vice president, genomic services, Eurofins Group, since 2008
Experience and Education:
Various positions at Eurofins (CEO of MWG Biotech, CEO of Eurofins Medigenomix/MWG Biotech, CEO of Operon Biotechnologies/Eurofins Medigenomix/MWG Biotech), 2005-2008
Vice president, primers and probes, Proligo (after acquisition of Genset's oligo business by Degussa and merger with Proligo), 2002-2005
Vice president, oligonucleotides (and other positions), Genset, France, 1992-2002
Postdoctoral fellow, National Cancer Institute, US, 1991-1992
PhD in molecular biology, University of Paris-Orsay, 1991
MS in engineering, Ecole Centrale de Paris, 1988

Founded in 1987
as an NMR-based wine testing business in France, Eurofins today provides a wide range of bioanalytical testing services in the areas of food, pharmaceuticals, and the environment. The company has more than 12,000 employees and over 160 laboratories in 32 countries.

Eurofins first entered the DNA testing arena in 2000, when it acquired Medigenomix in Germany. Its genomics portfolio grew with the acquisitions of GeneScan in 2004, MWG Biotech in 2005, and Operon Biotechnologies in 2007, which added laboratories in Germany, the US, India, and Japan. Those acquisitions helped the company build a presence in the research services market and provided its core business divisions with the expertise and facilities required to develop industrial-scale DNA testing.

In 2006, Eurofins-Medigenomix-MWG Biotech was among the first service providers in Germany to introduce sequencing on the 454 platform (GWDN 11/27/2006). While Eurofins does not disclose the types or numbers of sequencing instruments it has in house today, and does not allow visitors to enter its laboratories, the company offers next-gen sequencing services on the HiSeq 2000, Roche 454 GS FLX+, Roche 454 GS Junior, and, through a collaborator, on the PacBio RS platform.

Last week, In Sequence spoke with Bruno Poddevin, senior vice president of genomic services at Eurofins, at the company's "DNA campus" in Ebersberg near Munich, where Eurofins MWG Operon and Eurofins Medigenomix have laboratories and offices with more than 220 employees, offering a variety of genomic services, including Sanger sequencing, next-generation sequencing, oligonucleotide synthesis, genotyping, DNA forensics, and pharmacogenomics. Below is an edited version of the conversation.

What types of sequencing platforms — both Sanger and next-gen sequencing — does Eurofins have, and in which of your laboratories across the world are they located?

This is confidential information. But I would like to provide some context for this question. It's a very difficult decision for a company like Eurofins to decide which equipment to buy, how many pieces of each equipment to buy, when to buy, and where to set up the equipment. This is not the case in general for the vast majority of the business segments in which Eurofins is active, where the technologies are totally stabilized and under control.

For the field of sequencing, most of our resources today are in Sanger sequencing because this is where the service business is today, meaning Eurofins has the capability to provide a valuable service to customers, where we are capable of doing something better, faster, and cheaper than they can do, and they are willing to outsource this type of service to a service company.

How large is your Sanger sequencing business?

We are, as a matter of fact, today the number one company in Sanger sequencing services worldwide. There is no other company bigger than ourselves in the world offering Sanger sequencing — we are the company processing the largest number of Sanger reads per day, per month, per year.

Experts believe that Sanger sequencing is eventually going to move to some kind of next-gen sequencing platform. When do you see that coming?

At some point, but probably not before, let's say, 10 years, Sanger sequencing will be totally replaced by a new generation of sequencing. Next-gen sequencing will take over, will become a commodity type analysis, and we shall analyze the full genome of every living organism for many different types of applications, in humans, in food, in seed development, in environmental control, pathogen detection, and so on. How the transition will take place and for how long is difficult to predict.

From a business point of view, the shape of the curve will not follow the technology transition. The technology transition comes first, but the relationship between service provider and customers has some delay, and also the shape of the curve is different. What we observe right now is that Sanger sequencing services grow faster than ever. Why? On the one hand, there are more sequencing projects in general. The new capacity of next-gen sequencing technology drives a lot of interest, this drives a lot of budgeting, so a lot of money in R&D is being spent on sequencing. This money is being split between different types of technology. Sanger sequencing technology is still part of this, and receives a contribution from this budget increase. The second thing is that there is still a lot of synergy between Sanger sequencing and next-gen sequencing. Today, Sanger sequencing technology remains the most accurate technology, and as long as next-gen sequencing has not yet reached the same level of accuracy, for many applications, Sanger sequencing remains a mandatory complement to a sequencing project to have some confirmation. The third point is that many labs have stopped investing in Sanger sequencing platforms and decided to redirect their budget into next-gen sequencing technology. Consequently, they outsource Sanger sequencing more and more.

In terms of business impact for us, this is still a fast-growing segment, and I see this growth ongoing for several years until at some point, it may plateau and progressively be replaced by some next-gen sequencing technology that will have emerged and stabilized.

So have you invested in additional Sanger sequencing platforms?

Yes, we keep investing, first of all to address the demand we have. There are more and more universities that decide to close down their core facilities and want to rely on a supplier. Sometimes we already have a laboratory in place that can provide them with acceptable logistics, and we can offer the service from that existing laboratory. Sometimes, we create new laboratories that are connected to our global network. Here, we benefit from the scale of operations because our laboratories are all connected with the same LIMS, e-commerce system, and it's kind of a plug-and-play machinery.

How many of your labs provide Sanger sequencing in Europe right now?

We have hubs and we have what we call satellites, and we have many.

Can you talk about your next-gen sequencing business?

Sanger sequencing remains, from a business point of view and the scale of operations, what is the true business today. Nevertheless, I anticipate that the next-gen sequencing business will reach at some point a similar level of development, but it has not yet been reached. At the Eurofins level, it is not a stable market for us yet. This is why we are much more careful in terms of investment. Until now, none of the technologies has provided enough stability for us in order to decide to invest into a global network, a similar type of organization as what we have set up for Sanger sequencing.

The volatility of the technology is too high. If we had made the decision two years ago to buy 50 PacBio machines, it would have been a disaster. If three years ago, we had done the same with SOLiD, it would have been the same. What will happen with the Ion Proton coming soon, we don't know. What is going to happen with Oxford Nanopore, we don't know yet. Even Illumina and Roche have been changing their protocols so many times, which has a major impact for an industrial organization, because all the sample preparation automation you want to set up usually has to change, all the IT infrastructure that you set in place has to be upgraded at the same time, the bioinformatics solutions that you need to set in place also. So it is for sure not yet a stable environment to make a massive investment.

That being said, of course we could not just sit and wait, so in 2006 we started to invest in next-gen sequencing in order to learn about this type of technology. I think we were probably the first private laboratory in Europe to buy a Roche 454 sequencer, at that time the GS20. We have kept investing in order to have access to all the technologies, until one technology emerges and can be selected as the one in which we are going to invest at an industrial level to bring the service to the market. We are not yet at that point, but it will happen soon.

Why do you believe it will happen soon?

Because of customer demand. Genomic services within Eurofins works very closely with all other divisions — food, environment, pharmaceutical testing. We have had interactions with customers for years that try different approaches and technologies. Until now, there was no application that could be industrialized, meaning there is enough sample, on a regular basis, to be tested. Now, in some specific business segments, we have reached a point where some applications are mature enough so that it becomes a true industrial business. And because of that, we believe that we shall be able to safely invest in the infrastructure.

What are these applications?

I think the most advanced field is agrogenomics, with customers in the field of seed breeders, and also food manufacturers. This doesn't mean that there is no activity in other fields. For instance, it is obvious that in the pharmaceutical and clinical fields, a lot of things are being done, but from an industrial point, it is not advanced enough yet.

What kinds of next-gen sequencing services do you offer right now, and what are the most popular applications?

We offer sequencing on the Illumina, 454, and PacBio platforms. I think the vast majority of customers today ask for a combination of Illumina and Roche still. There is almost no demand for Pacific Biosciences, and there is no real demand for Ion Torrent yet.

We have a broad portfolio of applications. We specialize in de novo sequencing of genomes of any size, from planning the experiment and sample preparation with very specialized libraries to sequencing, using usually a combination of Roche FLX+ and Illumina, plus de novo assembly and also annotation. We also offer transcriptomics, where we have specialized libraries for sequencing the complete transcriptome, for expression profiling, detection of mutations. The next area is amplicon sequencing, which is still a Roche domain, and we also offer targeted resequencing and exome sequencing.

I think the Ion Torrent is a good technology, but it's not a good technology for a service company. There is no real added value we could bring with this type of machine today. It is an inexpensive technology, so if a customer wants to do this type of sequencing, he will buy the machine. We might be able to bring some value if, for instance, human exome sequencing becomes a routine type of analysis, and there is a need for a company that is able to provide thousands of such analyses per day, where you need to set up a true industrial organization. At that point, it might be a good time for us to do that, but we have not reached that point yet.

So a bit like Complete Genomics' business model, but for exome sequencing?

You see, Complete Genomics is a very good example because it really shows the gap between the technology, the science, future plans, and reality. They are probably very good people with very good technology, very good science; they are just too early for the market. And too early might mean in this field two or three years only, and the company can collapse because they are not there at the right time. That's exactly why it's a difficult question for us to decide what to buy and when to buy.

You were one of the first service providers to offer services on the PacBio, and you chose to provide those through a collaborator. How is that working out for you?

We had some projects where customers really had an interest in this technology. We have a relationship with an early-access customer of PacBio's platform, so we could work with them and be able to offer these services. Unfortunately, the results were not so good, so demand disappeared. The collaboration is still active but I don't think we provide a lot of these services today. It may change with the change of management at Pacific Biosciences [Michael Hunkapiller replaced Hugh Martin as CEO in January (IS 1/10/2012)]. My understanding is that they are trying to focus their technology on some very specific applications, and here, they might have a chance, maybe, because their machine might be the best machine for several years for some very specific application, but I don't know which one yet.

It is important to note that all over the world, there is a lot of next-gen sequencing capacity available. For every type of instrument, there are actually a lot that are only partially used, so having access to a sequencing run is not a difficult task. This is why, as the technology is changing, sequencing technology is not stabilized yet, and this capacity is available, we said there is no need for us to spend too much money buying a new fleet of equipment every six months.

But now, some basic infrastructure before and after sequencing is beginning to stabilize. Library preparation is getting more or less standardized. More and more, the IT infrastructure that you need to process the data becomes clearer. In terms of data analysis, it becomes clearer what type of analysis you will have to do, even if not all applications are well defined. When we decide on one specific type of equipment we want to make a massive investment in, the infrastructure platform is ready to host the equipment.

One platform you recently brought in house is the MiSeq. What's your experience with that?

We have one MiSeq here, among other equipment. First of all, we wanted to have a machine that is going to be clinically certified, so we can process some samples for the pharmaceutical industry. And as we can have quite a fast turnaround time with the MiSeq, it was better to have it here than in some other place. But I would say it is not an investment; it is still part of our approach to have access to all potential technologies. Sometimes we buy one machine, sometimes we rent one, sometimes we work in a collaboration. If we decide that MiSeq is a relevant technology for which there is a specific market, we shall buy more than one.

Do you currently offer clinical sequencing, and how is that regulated?

We have all certifications [for clinical laboratories] available in Europe, but there is not yet any specific certification to process clinical samples for sequencing. So in order to validate our work, we go through audits by our customers on top of the ISO certification we already have in our lab.

We also have CLIA labs in the US, and we have laboratories, including one laboratory here [in Germany], that are working with clinical samples, including sequencing. That's an important future market for us in connection with the pharmaceutical testing division of Eurofins. All big pharmaceutical companies are customers of Eurofins today, and we do have, as part of the Eurofins organization, a central lab business, and we are equipped and certified so we can process clinical samples for them.

Are you already using the MiSeq for clinical sequencing?

Yes, as well as the Roche 454 Junior. But the majority is done with Sanger sequencing, because that's the gold standard in clinical trials, and also in the diagnostic segment. We now see the first development of assay portfolios being shifted to next-gen, and we are working extensively with customers on validating next-gen sequencing.

Do you believe clinical next-gen sequencing is going to be an easier market here in Europe than in the US because of the different types of regulation?

The US is more advanced in using this type of technology for clinical work. Not only because they have already a type of certification in place, the CLIA certification, … but also because they have more flexibility in insurance payments for patients, which are not yet at that level in Europe, and that makes a big difference.

Last year, Eurofins acquired Lancaster Laboratories, which has a CLIA lab in the US. They are working to develop with our customers a protocol to use sequencing and next-gen sequencing. That's a good benefit we have, by working with our colleagues in the US, to learn about how things are going in the US, because at the end, from an operational point of view, the way clinical samples are being handled in the US will probably be very close to the way these types of samples will have to be handled in Europe. We closely cooperate so we can have this type of setup in Europe, too.

Where do you see the clinical market for sequencing growing?

Oncogenomics is probably going to be the first beneficiary from the technology. But there are also sectors like infectious disease that might benefit soon, because next-gen sequencing offers a breakthrough approach for pathogen identification. There are still a lot of infectious diseases treated for which we do not know the cause. But of course in the future, in 20 years, I don't think anybody would think that we would not sequence the whole genome of every individual, which would be valuable for any type of diagnostic later on.

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