The market share of ultrafast sequencing machines on the total sequencing market is set to expand rapidly. In April 2010, Roche daughter 454 Life Sciences (Branford, US) is launching a new system especially designed for...
The market share of ultrafast sequencing machines on the total sequencing market is set to expand rapidly. In April 2010, Roche daughter 454 Life Sciences (Branford, US) is launching a new system especially designed for individual researchers. The size of a laser printer, the machine has read lengths of 400-500 base pairs and will be sold at a fraction of the cost of other current high throughput sequencing systems. 454’s GS Junior addresses a market that is estimated to be 10-100 times larger than that for the current US$500,000 machines, which are aimed at just 1,000 core labs and sequencing centres worldwide. The new development looks set to make next-generation sequencing available even for smaller labs. EuroBiotechNews spoke with Christopher McLeod, President and CEO of 454 Life Sciences, about what the new system can do.
Roche/454 recently announced it was launching the GS Junior System – a new machine for next-generation sequencing – by the spring of 2010. What are its features and its target markets?
With the GS Junior, we will make next-generation sequencing available to the indi- vidual researcher. Up to now, access to high-throughput sequencing was still primarily limited to large research facilities because of IT infrastructure requirements for data analysis, and the cost of capital equipment and disposables. We want to change that with a new system that is tailored to the needs of the individual lab. The GS Junior is a benchtop system that offers a throughput of over 35 million high-quality, filtered bases per run – which is about 100,000 reads. The system needs 10 hours for sequencing, and an additional 2 hours for data processing. Like its big brother, the GS FLX System, it will offer read lengths of 400 base pairs on average at 99% accuracy. All 454 data processing can be performed on an accompanying computer with a pre-installed software package that includes easy-to-use tools for assembly, mapping and variant detection. We will launch our new system by March or April 2010.
What was behind the idea to bring this kind of personal sequencer to market?
DNA sequencing has become more affordable with the introduction of 454 sequencing and other high-throughput sequencing technologies. We are continuing to try to improve the performance of our technology, including our flagship system the GS FLX system – to increase the throughput and reduce the cost per base of sequencing. Recently, we announced that we will double the read lengths of our current GS FLX Titanium Chemistry kits from 400-500 bp per read to 800-1000 base pair reads in 2010, which is comparable to that of Sanger sequencing. In terms of throughput, we are far beyond Sanger sequencing because of its 500 times faster throughput and reads that are 50 times cheaper. One of the strongest applications of 454 Sequencing systems is analysing genes or genetic regions in great depth – whether to identify rare mutations such as in HI-Viruses, or to identify haplotypes within the MHC region, which includes a critical set of genes involved in immune response. However, the capabilities of the current GS FLX System are often too great for this type of research. You don’t need to have a US$500,000 instrument and a US$5,000 run cost if your goal is to analyse a limited number of genes. So what we have heard from our customers is that they would like a less expensive instrument; one that doesn’t need the same throughput, but is significantly less expensive per run. We have delivered on these needs with the GS Junior System. This new system is truly targeted for the benchtop in the individual lab, as opposed to core labs or genome centers. With the GS FLX we revolutionised sequencing. Five years ago, high-throughput sequencing was really only being done in 10-12 genome centers, because it required tens of millions of dollars of investment to have the kind of throughput that you would need. With our GS FLX System, you can achieve this level of sequencing power with a single instrument. So now high-throughput sequencing has expanded in many more labs, such as core labs. But now with the GS Junior System, we want to become for biology what personal computing has been for the IT branch. It really is an individual piece of research equipment.
According to your estimates, how many additional customers does it address?
Our GS FLX System targets a market of perhaps 1,000-2,000 customers worldwide. In comparison, our new GS Junior System, which costs one fifth of the price, targets all the tens of thousands of labs that have, for example, a thermocycler. It targets all research groups that carry out targeted sequencing for identifying genomic regions that are associated with disease, all groups that carry out genotyping or de-novo microbial genome sequencing, as well as those pursuing metagenomic studies or seeking to detect novel pathogens.
What are the advantages of Roche/454’s two sequencing systems compared to the systems offered by Illumina and ABI/Life Technologies? What do you predict for its market position in applications such as re-sequencing, de-novo sequencing, transcriptional profiling, miRNA sequencing, amplicon sequencing, and so on?
GS Junior will target the scientist in the individual lab. Whether or not our competitors decide that this is a market they want to address – and whether or not their technologies will scale as well – is an open question. Comparing the GS FLX with the offerings from Illumina or the ABI SOLID system, their systems are capable of generating more bases with a larger number of reads, but significantly shorter read lengths. The strength of our technology is in applications that require long, high-quality reads. This includes almost every type of de-novo assembly; i.e when you are sequencing an organism for the first time and building a reference sequence, searching for the presence of rare variations in viruses, or if you want to identify which organisms are present in metagenomic analyses. On top of this, we think that our system has some very clear speed and data analysis advantages. Because you can complete a sequencing run in less than 12 hours with 454 sequencing, researchers can get results very quickly. Our competitors need days, if not weeks to generate results. Secondly, what really is becoming the bottleneck now is not the sequencing itself, but how to analyse the data at an acceptable cost and then to transform the data into useful , biologically-relevant results.
The GS Junior has a kind of automated assembly software for users who are unfamiliar with bioinformatics. Can you give us some details about that feature?
That feature is part of the overall software design. Whether the task is to assemble a whole genome sequence de novo or to look at genomic variation caused by SNPs, deletions, copy number variations or genomic re-arrangements, in both cases we have software tools that will make it easy for the GS Junior user to go from experimental design to analysis of the data. Another point is that if you are going to resequence a genomic region, what you are doing is mapping against a reference genome. The problem you run into is that you may miss certain types of variations because you are forced to map against a reference. We think that certain experiments need to use de-novo assembly. And we provide an automated solution to do this with our GS De Novo Assembler software.
What advantages does the GS Junior offer compared to the GS FLX System?
The benefit of the GS Junior System is that it is a much more affordable solution. It can be acquired by individual scientists, and give very quick answers to research questions. In comparison to the GS FLX, the GS Junior System has a lower throughput – but the cost per run and the instrument cost is lower.
What research applications is the the new system designed for?
The system is sized for a number of different applications. If you wanted to analyse drug resistance in HIV in the past, and do it economically, you would need to run 40 or 50 samples at a time. With the GS Junior, you can do the same analysis economically with 10 samples, without the need to wait for enough samples to perform a sequencing. For certain types of research, you don’t need the full throughput of the GS FLX. This is also true if you’re looking at certain genes for potential genetic disease, which you can do with a handful of samples, depending on the experimental design. As mentioned before, the system is also capable of sequencing whole viral or microbal genomes de novo in a single run. You can also use the system for research into individual bacterial genomes.
Currently, the GS FLX as well as the GS Junior are for research use only. When will we see systems approved for use in the diagnostics market?
We are speaking with regulatory authorities and experts in the US and in Europe about what is required to bring a system into that market segment. The GS FLX System is already used in research to identify biomarkers. Now we want to see it approved for use in diagnostics because there is tremendous interest amongst our customers.
Have next-generation sequencers already replaced Sanger sequencers, or will these continue to have a significant market share?
What we can see about the impact of high throughput sequencing from ABIs financials is that there is still a substantial market for Sanger sequencing. However, we think that this will erode, as the capabilities of the high-throughput platforms are better suited for more and more applications. Nobody can predict if they will be completely eliminated, but the GS Junior and the GS FLX Systems will replace Sanger sequencing where they offer clear advantages to customers, as in de-novo sequencing. In terms of the current market share, there are estimates that more than half of the total sequencing market is being covered by new-generation high-throughput sequencing. But it is difficult to extract the exact numbers from our competitors.
There have been several announcements of single molecule sequencing platforms. How far along are they?
Collectively, the risk that most single molecule approaches have is that you only have one chance to record a base, and if you miss it you could have an error. What we have seen so far is Helicos, with the only single-molecule platform that is commercially available. They tend to compete more with the Illumina and the SOLID platforms, but because they lack the read length quality for de-novo sequencing, an application in which 454 Sequencing remains unmatched, were not able to carry out high-throughput de-novo sequencing.
Luxembourg has appeared from nowhere with an initiative to set up a European center for diagnostic biomarkers, while it’s government has set aside EUR140m to reach some ambitious goals. To speed up development, Luxembourg looked...
Jeannot Krecké is a busy man these days. Luxembourg’s Economics Minister is pulling every string he can to put the little country on the biomedical map in Europe. In total, his government has earmarked EUR140m in funding until 2013 – money that will be used to set up a complete new research infrastructure. “If we want to attract life sciences to Luxembourg, then we need an academic background,” Krecké told EuroBiotechNews.
In terms of research, the Grand Duchy has a lot of catching up to do. Its three Centres de Recherche Public (CRP) – Santé, Henri Tudor and Gabriel Lippmann – were only founded at the end of the 1980s. Luxembourg didn’t even have a Research Ministry or a research budget until 1999. Six years ago, the University of Luxembourg was born. “Back in the old days, the philosophy was that young people don’t need a university in Luxembourg, they have to study abroad,” explains Research Minister François Biltgen. But that attitude has changed in the last few years. Now Biltgen is proud to have a university that offers Bologna-conform studies right from the start. And research has joined higher education at the top of the country’s wish-list. The Luxembourg Centre for Systems Biomedicine (LCSB) and the Integrated Biobank of Luxembourg (IBBL) are the visible signs of that new strategy. They were both built from scratch. “We have to provide credibility,” Krecké says.
Even before the onset of the financial crisis, the minister was lobbying for more diversity in the country’s economy and a move away from the banking sector. More than 150 financial institutions have offices in Luxembourg, and almost a third of the country’s gross domestic product is earned with financial services – the result of beneficial regulatory conditions and an attractive tax environment. But Krecké says this strength also hides a weakness: “The strong concentration of growth toward a single sector makes our country vulnerable.”
Biomarkers as a niche strategy
Since Krecké took office in 2004, the government has been looking for alternatives, and one sector of interest was biotechnology. In 2006, the CRP-Santé published a report with an interesting conclusion. The biomedical research landscape is small, it said, and the majority of the 56 companies active in the field are pharma firms.
Since 2008, the path has grown clearer.Luxembourg doesn’t want to pursue expensive drug development, but instead diagnostic biomarkers and personalised medicine. This goal was firmed up in June 2008 with a strategic partnership deal involving three renowned US-research institutes.
In concrete terms, this means that both of the new research centres have established a close relationship with the US research community. Whereas the Translational Genomics Research Institute (TGen) under Jeffrey Trent in Phoenix has been helping with the start-up of Luxembourg’s biobank, the LCSB has been working closely with the Seattle-based Institute of Systems Biology (ISB) under Leroy Hood, the founder of a number of biotech companies – among them Amgen, Rosetta and Applied Biosystems. One of the biobank‘s first customers will be a lung cancer project from the Partnership for Personalized Medicine (PPM) in Phoenix, which was initiated by Nobel laureate Leland Hartwell. The overall goal of this project, in which the CRP-Santé is also taking part, is to identify biomarkers for lung cancer. “With these three cooperations we have already received a lot of publicity,” sums up Krecké when discussing the first phase. “In the long run, we will also benefit from it economically.”
And the minister has provided the regulatory basis to do so. In 2007, he passed a law that is not only attractive for Luxembourg’s companies. It states that anyone who creates intellectual property in Luxembourg or in cooperation with one of its research entities can receive tax rebates of up to 80% on the revenues generated by this IP. Another law was passed granting companies generous support for R&D activities. A majority of the millions reserved for the biomedical offensive will be channeled into technology transfer. Spin-offs derived from the partnership with the US institutions are to be started as bi-national firms, with a consequent division of patent rights. There are also incentives for researchers to patent first and publish later. In spite of the rosy description though, there are still a few prospective pitfalls. This is especially true for the labs.
Critics from private laboratories
“To date, laboratories are only allowed to register as a non-incorporated firm in Luxembourg, not as an incorporated entity,” criticises Jean-Luc Dourson, the President of Luxembourg’s Federation of Medical Analytic Laboratories (FLLAM). The major problem is a laboratory law that falls under the purview of the Ministry of Health. Initiated in 1984, it places medical analysis firmly in the hands of doctors. Based on that, a range of clinical laboratories have emerged that are proving a lucrative source of income for the clinics – due to the fact that laboratory analysis is directly reimbursed by health insurance schemes. For private sector competitors, it’s an attractive market. To date, three companies are active in the area: Ketterhill, Laboratoires Réunis and Laboratoires Les Forges du Sud. Nevertheless, the laboratory law inhibits cooperation with international partners, and limits its working radius. “We are allowed to take blood and urine samples, but not to analyse tissue,” says Dourson. Possible solutions are currently the focus of talks between Krecké and Health Minister Mars Di Bartolomeo. For the Economics Minister however, the situation is clear: “We have to cut a fire break between the national insurance and economic development in the health sector.”
Meanwhile, the establishment of research infrastructure is in full swing. In March of last year, international biobank expert Robert Hewitt, President of the International Society for Biological and Environmental Repositories, was appointed Chief of the IBBL. The biobank only recently moved into its new facilities. Hewitt is aiming to establish the IBBL as a centre with high technical expertise when it comes to storing and analysing bioprobes – one that will cooperate with others under the roof of the European biobank-network BBMRI. Last summer, an LCSB-head was found in German science manager Rudi Balling, former chief of the Helmholtz-Center for Infection Research in Braunschweig. “During the next four to five years I will have up to 100 employees,” Balling claims. The first will initially settle in the US before coming back when the infrastructure is ready.
The close US-relationship offers advantages. In 2009, Eric Tschirhart, the administrative head of the University of Luxembourg, told a local newspaper “that we will get a push in terms of knowledge during five years of cooperation with the ISB that would take 25 years to acquire on our own.” The first projects have already begun.
But the American connection also increases pressure. “If an initiative of this stature goes wrong, we can forget biotech in Luxembourg for the next 30 years,” Tschirhart believes.
Researchers aren’t worried. They feel lucky to be setting up an infrastructure in a special environment. “I already received a request from a banker who is thinking about donating to research,” says Balling.
Good support for start-ups
Luxembourg’s big advantage is the nearby banks, which will also aid future start-ups. Last year alone, the VC Fonds Vesalius Biocapital (EUR75m) – which has an office in Luxembourg – began a partnership with the CRP-Santé to support young biotech companies. Krecké is also planning his own risk-capital funds with a focus on companies in the field of personalised medicine. This fund will be established in a close relationship with the German Hopp BioTech, the investment company set up by former SAP founder Dietmar Hopp. “We only have to clear up the final details,” according to Krecké, who added that “Luxembourg will do its share, but I also negotiate with partners.”
Djalil Coowar has already gone a step further. In 2006, the neurologist at the University of Luxembourg founded Axoglia Therapeutics S.A together with French colleagues. Since then, he’s been able to count on Kreckés financial and political support. Axoglia is not just the young university’s first spin-off – it’s also the first in biotechnology.
Systems biology is aimed at achieving a holistic understanding of living organisms, while synthetic biology seeks to design and construct new living organisms with targeted functionalities. Genome sequencing and the fields of...
Transcription network inference – which reverse engineers the transcriptional control of an organism from high-throughput gene expression data – offers valuable insights into the induction/inhibition relationship among genes and their regulating factors. Gene regulation can potentially proceed through many mechanisms, including post-translational modifications of transcription factors, and it can also involve many factors at the metabolic, enzymatic, and extra-cellular signaling levels that are not readily measurable at the genome-scale level. The average working hypothesis when making deductions about transcription networks therefore generally assumes that only expression levels of transcription factors significantly contribute to gene regulation. There are three common approaches to inferring transcription networks . Logical network inference methods represent genes as Boolean On/Off states connected by binary interactions, and then proceed to explore the available topologies. Alternatively, a statistical approach can be used to evaluate the mutual dependence between each gene pair in all measured conditions in order to infer the connectivity of the genes. Based on differential equations, the third approach captures the dynamic evolution of gene transcripts and their regulating factors. It can offer a more detailed analysis of the network, but due to its high computational cost, this approach is limited to small groups of genes. The large number of genes in a typical organism causes a high ratio of unknown variables versus data points; nevertheless, the problems posed by an under-determined system can be alleviated with additional information from verified interactions – for example, from DNA sequence binding motifs or data from comparative genomics. More efforts need to be made to incorporate non-transcription factors in the transcription network analysis, and to improve the accuracy of the inferred connections.
A metabolic network is a dynamic system of reactions that responds to the availability of nutrient sources and the surrounding conditions of an organism. Until now, the determination of reaction kinetics at the genome-scale level remains an overwhelmingly demanding task in terms of experiments. For this reason, the pseudo-steady-state assumption for example – which states that the concentration of each metabolite is constant over time – is generally used to simplify the relationship among metabolites to a linear stoichiometric model, thereby abolishing the need to use unknown reaction kinetics. Such models are constrained by biological limits such as reaction reversibility, maximum possible enzyme activity, and gene activity (e.g. determined from transcriptomics data). There are generally two different approaches to tackling linear stoichiometric genome-scale models: optimisation-based and unbiased analysis. The optimisation-based approach assumes the metabolic flux distributions at steady-state are regulated so as to achieve certain objectives. For example, Flux Balance Analysis calculates the optimal metabolic flux distribution among all possible sets of solution for a specific objective such as maximal growth yield or compound yield. It can also assess the viability of mutants  by evaluating the feasibility of biomass synthesis. Sometimes the assumption of perfect optimality in biological systems may not be true, and thus Flux Variability Analysis may be used to calculate sub-optimal solutions to give a range of possible flux distributions. Selecting the optimal mathematical function to represent the biological objective to optimize (cell growth, biomass or energy production) remains an open problem. When addressing the subject of mutant selection for example, the decision of gene-knockout could be assisted by the OptKnock method ,which identifies knockout targets for bioproduction by maximization of both cell growth and the yield of the metabolite of interest. A schematic diagram of gene-knockout selection based on genome-scale metabolic modeling is shown in Figure 1. The changes in flux distribution between the wild-type and mutants can be predicted by the Minimisation of Metabolic Adjustment or Regulatory On-Off Minimisation methods. The first of these assumes that mutants tend to minimise variations to metabolic fluxes . The second minimises the number of adjustments in the reaction network . Both methods take into account that cells may not function at the optimal state, and mutants may evolve slowly before arriving at the new ideal flux distribution. They are both useful, with one performing at times better than the other depending on the situation.
Topologies of networks
The unbiased analysis approach investigates the topology of the metabolic network to reveal its fundamental properties. For example, Elementary Flux Modes indicate all minimum feasible sets of metabolic pathways to maintain steady-state. The Extreme Pathways method evaluates the network in a similar way, but treats internal reversible reactions differently by splitting them into two separate reactions, resulting in different practical aspects in real metabolic systems . These two methods, however, can become intractable in computational terms for genome-scale networks. Alternatively, the qualitative relationship among fluxes – how changes in one flux would affect another flux in a large network – can be computed by the Flux Coupling Finder method. This assigns relationships to reactions based on the extent of their mutual influence. Genome-scale metabolic modeling can be used to assist over-production of compounds of industrial or clinical interest, to understand the metabolic properties of certain pathogenic organisms , or to engineer cells to modify their functions.
Prediction of genetic regulation
Coupling the models for regulatory networks and metabolic networks to predict the effect of genetic regulation on metabolic fluxes is still an open challenge. In order to extend the capability of genome-scale metabolic models to describe transient dynamics, several approaches have been adopted to compromise the lack of detailed quantitative reaction kinetics from an entire organism. For example, reactions in a signaling network can be assumed to be fast, and thus simplified using quasi-steady-state. And slow reactions like biomass synthesis can be approximated in a time-delayed manner . Another suggestion is to use a linear sum of logarithmic terms based on stoichiometric relation to approximate unknown enzyme kinetics . It is important for models to capture dynamic responses in biological systems, since these are known to be of a highly non-linear nature. The efficient engineering of cell hosts (‘chassis’ ), requires synergy from both experimentation and a predictive genome-scale model that integrates the knowledge of all cellular activities.
In efforts to increase the predictive capability of large transcription and metabolic network models, many challenges remain to be overcome, among them the quality of gene annotations and genes with unknown functions. Modeling and experimentation at the genome-scale are destined to grow closer in the future, enabling us to understand the biological world in ever greater detail, and synthesize more accurate biological devices. The ability to infer transcription networks correctly and predict metabolic responses is especially important for synthetic biology, where synthetic gene regulatory networks are built within cell hosts  or novel biocatalytic circuits are designed to reprogramme cellular metabolic patterns . A ‘blueprint’ of the interactions among genes, proteins, metabolites, and regulatory factors in a host cell from systems biology would form the basis for studying artificial manipulation of the cell in synthetic biology. Together, the two fields will continue to expand our knowledge of the properties of living organisms, and open new avenues for biotechnological development.
 Agapakis, C.M., Silver, P.A., Agapakis, C.M., Silver, P.A, Synthetic biology: exploring and exploiting genetic modularity through the design of novel biological networks. Molecular BioSystems (2009), 704-713.
 Carrera, J., Rodrigo, G., Jaramillo, A., Towards the automated engineering of a synthetic genome. Molecular BioSystems (2009), 733-743.
 Bansal, M., Belcastro, V., Ambesi-Impiombato, A., Bernardo, D.D., How to infer gene networks from expression profiles. Mol. Syst. Biol. (2007), 78.
 Oh, Y.K., Palsson, B.O., Park, S.M., Schilling, C.H., Mahadevan, R., Genome-scale reconstruction of metabolic network in Bacillus subtilis based on high-throughput phenotyping and gene essentiality data. J. Biol. Chem. (2007), 28791-28799.
 Burgard, A.P., Pharkya, P., Maranas, C.D., Optknock: a bilevel programming framework for identifying gene knockout strategies for microbial strain optimization. Biotechnol. Bioeng. (2003), 647-657.
 Segre, D., Vitkup, D., Church, G.M., Analysis of optimality in natural and perturbed metabolic networks, PNAS (2002), 15112-15117.
 Shlomi, T., Berkman, O., Ruppin, E., Regulatory on/off minimization of metabolic flux changes after genetic perturbations. Proc. Natl. Acad. Sci. U. S. A. (2005), 7695-7700.
 Papin, J.A., Stelling, J., Price, N.D., Klamt, S., Schuster, S., Palsson, B.O., Hierarchical thinking in network biology: the unbiased modularization of biochemical networks. Trends Biotechnol. (2004), 400-405.
 Oberhardt, M.A., Puchalka, J., Fryer, K.E., Martins dos Santos, V.A.P., Papin, J.A., Genome-scale metabolic network analysis of the opportunistic pathogen Pseudomonas aeruginosa PAO1 J. Bacteriol. (2008), 2790-2803.
 Lee, J.M., Gianchandani, E.P., Eddy, J.A., Papin, J.A., Dynamic analysis of integrated signaling, metabolic, and regulatory networks. PLoS Comput Biol (2008), e1000086.
 Smallbone, K., Simeonidis, E., Broomhead, D.S., Kell, D.B., Something from nothing: bridging the gap between constraint-based and kinetic modelling. FEBS J. (2007), 5576-5585.
 Andrianantoandro, E., Basu, S., Karig, D.K., Weiss, R., Synthetic biology: new engineering rules for an emerging discipline. Mol. Syst. Biol. (2006), 2006.0028.
 Cantone, I., Marucci, L., Iorio, F., Ricci, M.A., Belcastro, V., Bansal, M., Santini, S., di Bernardo, M., di Bernardo, D., Cosma, M.P., A yeast synthetic network for in vivo assessment of reverse-engineering and modeling approaches. Cell (2009), 172-181.
 Landrain, T.E., Carrera, J., Kirov, B., Rodrigo, G., Jaramillo, A., Modular model-based design for heterologous bioproduction in bacteria. Curr. Opin. Biotechnol. (2009), 272-279.
Prof. Dr. Dipl-Ing Vitor A.P. Martins dos Santos
Systems and Synthetic Biology Group
Helmholtz Center for Infection Research
Inhoffenstr. 7, 38124 Braunschweig, Germany
Tel./ Fax: +49-531-6181-4008/-4199
from 03/2010: firstname.lastname@example.org
Politics / Law
Europe is to receive a new Super Commissioner for biotech, as well as the largest budget for research the bloc has ever granted. Even before the start of hearings considering the 26 Commission nominees that began in mid-January,...
Barroso foresees Dalli taking over responsibilities for the European Medicines Agency (EMA). As chief of the European Food Safety Authority (EFSA), he will additionally be in charge of overview for all market authorisations in agribiotech, cloning or assessing new technology. The new commissioner will also take the helm at the EU’s Plant Variety Office and the European Centre for Disease Control (ECDC), and will assume competencies for consumer protection from the Environment Directorate-General, together with those for the Executive Agency for Health and Consumers (EAHC). The reshuffling appears to have resulted from the conflicts that arose between up to 5 Commissioners in Barroso’s last team in the areas of GMOs, cloning and other new technologies.
Positive EP hearing
In his European Parliament hearing, Dalli made it clear that he will seek to push the stalled pharma package, saying he wants to move forward quickly with non-controversial areas like pharmacovigilance and counterfeit medicines. But he was more reserved concerning direct-to-consumer advertising of drugs (see EuroBiotechNews 11-12/2009) by the pharmaceutical industry, saying “we have to bring more patient perspective in the proposal.”
“The underlying theme of my work will be Patients First,” he said, but underlined that this “did not exclude a strong commitment that the pharma industry remain competitive.” He also wants to focus on prevention, which could be good news for the diagnostics industry if plans include predictive diagnostics tests. In agribiotech, Dalli indirectly backed the EFSA by saying that science must be the basis for assessments of new technologies. To cope with attacks on the agency, which made headlines after a member of its GMO panel moved to an agribiotoech company, he has proposed regular reviews of independence in various agencies. In the ongoing debate on foods from cloned animals, he said: “I hope that within a year we can come up with a report on how to tackle the cloning issue.”
Confirmation of the new Commission is expected after the hearings are wrapped up in February.
The new EU Commissioner-Delegate for Health and Consumer Policy made his case to the European Parliament in January, and has now been granted a revamped portfolio of previously distinct health-related organisations and...
The new Commissioner has a strong economic and financial background, and more recently social policy responsibility in Malta. So it was not a huge surprise that his presentation to the Parliament focused on patient and consumer-driven approaches. And since biotech in Europe is still struggling to make money out of its research, Dalli’s strong statement for demand-driven health technologies was also a welcome sign, indicating he will focus strongly on funding to maturation. Until now, Europe’s localised, piecemeal approach to technology scouting and funding has produced many lemming companies – following one another over the cliff of underfunding and bankruptcy.
His presentation also placed heavy emphasis on pharma, and fed hopes that Dalli might be the one to help smooth the rocky path that is the EMEA approval process. More worrisome was that he didn’t mention the biotech SMEs that fuel the pharma pipeline. Perhaps a temporary omission from a man new to the job, but SMEs are the champions of early stage technologies.
In health care, the new Commissioner came out clearly in favour of prevention as opposed to therapy, which seems to promise significant potential for earlier diagnosis and monitoring technologies. Dalli has a background in economics and finance history. He knows how much illness costs, and wants investment in prevention now to save in the long term. But can he persuade policymakers at European and national levels to open their pockets to pay for goals that will not be measured in a single electoral cycle?
He also addressed food safety and nutrition in detail, and the new Commissioner is convinced that food needs to play a bigger role in disease prevention. Whether those words will translate into actions and the creation of a biotech-driven food sector remains to be seen.
His cautious party line on cloning, GMOs and nanotechnology was no surprise. There’s little doubt that Europe will continue its careful course in all three areas. Stem cells were not mentioned in the same breath as those technologies, indicating they could be gaining more widespread acceptance. The Commissioner’s assertion that all decisions will be based on scientific advice was certainly welcome, but has not stopped politically-motivated agendas in the past. It will probably remain business as usual when it comes to hot-potato topics.
To summarise: John Dalli appears to have clear opinions on what should drive healthcare development, as well as on the importance of preventing illness tied to economic and innovation development. The big question is – can he follow through with targeted policy? Maybe. Just don’t expect miracles.B
Reykjavik – Iceland's deCode Genetics has reimmerged as a private biotechnology company following its purchase from its former parent company by Saga Investments LLC, a consortium that includes Polaris Ventures and ARCH Venture...
Reykjavik – Iceland's deCode Genetics has reimmerged as a private biotechnology company following its purchase from its former parent company by Saga Investments LLC, a consortium that includes Polaris Ventures and ARCH Venture Partners.
Led by CEO Earl “Duke” Collier, previously an executive vice president at Genzyme Corp, plus Executive Chairman and President of Research Kari Stefansson, deCode ehf will build on the expertise in genome scans, diagnostic disease risk tests and contract service genotyping, sequencing and data analysis that it developed as a subsidiary of deCODE genetics, Inc. The company‘s IP was sold to Saga Investments LLC by deCode Genetics Inc, before the company changed its name to DGI Resolution Inc and entered liquidation.
Politics / Law
Darmstadt/Berlin – Cultivation of GM maize in the EU fell sharply in 2009, according to figures from transgen.de. The most active country is still Spain, which makes up more than 80% of all GM cultivation. In 2009, European...
Darmstadt/Berlin – Cultivation of GM maize in the EU fell sharply in 2009, according to figures from transgen.de. The most active country is still Spain, which makes up more than 80% of all GM cultivation. In 2009, European farmers planted about 20 percent less than the previous year of Monsanto’s MON 810, the only approved GM maize within the bloc. While the cultivated area in 2008 amounted to 108,000 hectares (see more…), it peaked at 86,000 ha of MON 810, just 0.1% of the worldwide GM crop acreage. In Germany, the Czech Republic, Romania, Slovakia, and Spain, cultivation declined by a total of 19,000 hectares. However, the picture on the world markets appears to be different to the situation in Europe. After China gave the go-ahead to large-scale cultivation of insect-resistant GM rice in December (see more…), experts now expect the GM crop area to expand by more than 30 million hectares in the near term. According to figures from the International Service for the Acquisition of Agri-biotech Applications (ISAAA), which is to release precise global production figures in February 2010, GM crops were grown on 125 million hectares in 2008.
Germany has launched Europe’s first civil high-throughput screening facility for high-risk infectious agents within the framework of ERA-NET PathoGenoMics. The novel bio-safety level 3 (BSL3) unit at the Max Planck Institute for...
Germany has launched Europe’s first civil high-throughput screening facility for high-risk infectious agents within the framework of ERA-NET PathoGenoMics. The novel bio-safety level 3 (BSL3) unit at the Max Planck Institute for Infection Biology in Berlin was inaugurated in mid-September by representatives from the German Research Ministry and the Max Planck Society. The next step will be to carry out functional RNAi screens in flu-infected host cells to find new targets and drug leads.
Circumventing microbial resistance
Identification of drug candidates against multi-resistant bacterial pathogens will also be a priority for the team of Max Planck researchers under Professor Thomas Meyer. Infectious diseases are still the world’s second most frequent cause of death in spite of improvements in hygiene, vaccination campaigns and further development of antibiotics. Researchers currently use two scientific strategies to nail down promising drug candidates. The hypothesis-driven approach focusses on the investigation of distinct virulence processes, while the global analysis approach employs high-throughput technologies and bioinformatics to identify the most critical factors in pathogenesis. The latter has been gradually gaining in importance. Within the framework of ERA-NET PathoGenoMics, the Max Planck Society and German Ministry of Education and Research (BMBF) have now kicked-off Europe’s first high-throughput screening facility for highrisk pathogenic agents. The BSL3 (biosafety level) unit comprises a screening robot, as well as the necessary periphery infrastructure such as molecular biological BSL3 labs and state-of-the-art high-throughput microscopy and read-out devices. Its prime purpose will be to conduct screens with bacterial pathogens causing plague, typhus, tuberculosis and other deadly diseases.
First project: RNAi screen against pandemic influenza
The recent flu pandemic has also led to an expansion of that brief. The institute is now preparing to screen for drug candidates against pandemic influenza and is searching support from the EU FP7 HEALTH programme. Targeting host-cell compounds The researchers will be testing a new strategy for overcoming the ability of flu viruses to change their phenotype, thus escaping current therapeutic regimes. Influenza A viruses exhibit intrinsic mechanisms for generating altered viruses: their genome consists of 8 genome segments that can be quickly re-assorted upon viral coinfections, a process called antigenic shift. Such viral recombinants exhibit severely altered surface structures, allowing them to slip under the immune system’s radar. Moreover, virus replication facilitates the generation of point mutations, giving rise to a steady ‘antigenic drift’ and viral escape mutants. Such viral escape mutants clearly hamper efficacy of available flu treatments, as existing anti-virals are directed against bona fide viral targets, which risks generating therapy resistance. The new project is aimed at benefiting from the fact that viral infection and replication intimately depend on factors provided by the host cell.
Focus on targets essential for the virus
The MPI team will target host cell factors that are dispensable for the host but essential for virus replication. Using high-throughput RNA interference technology, they will scan the entire human genome for critical determinants of infection. Identification of these determinants will lead to promising therapeutic solutions for the most important human virus infections. The approach can also be applied to other viral infections with pandemic potential, according to Meyer. “During the past few decades, new viral diseases such as AIDS, SARS and Nipah Virus Encephalitis have emerged. On top of that, known viral agents are in the process of changing their behavior and location because of i.e. climatic variations or international traffic.” Meyer is convinced that the new project represents a necessary and timely search for suitable targets and effective drugs against devastating infections that have high mortality rates.
Politics / Law
Brussels/Strasbourg – John Dalli, the designated Super Commissioner for Biotechnology has set out his future priorities as Health Commissioner of the European Commission. In a document published on 23 December by the European...
Brussels/Strasbourg – John Dalli, the designated Super Commissioner for Biotechnology has set out his future priorities as Health Commissioner of the European Commission. In a document published on 23 December by the European Parliament, Dalli made clear that "any policy on issues such as cloning, nanotechnology will continue to be based on scientific facts, and will respect ethical values while striving to enhance Europe’s innovative drive and at the same time eliminate risks to our citizens. Equally in the area of GMOs, science will continue to guide our actions, and I will put into practice the President of the Commission's guidelines concerning cultivation." (see more…). According to www.agrarzeitung.de, this means that Dalli wants to give more flexibility to the EU member states concerning the cultivation of genetically modified crops. Furthermore, Dalli has stated that he would like to push for better regulation in the highly regulated internal market for animals, plants, seeds, food and feed, in order to boost the European agro-industry, and to stimulate innovation, while also respecting the health and interests of consumers and the environment. In this area the overarching principle remains 'safety first'. But this would not mean zero risk. He also appears to hope to follow an industry-friendly approach in the area of drug development. Dalli said: "I look forward to the upcoming evaluation report on the functioning of the European Medicines Agency, and in this context to evaluating whether there is scope for measures whereby we can optimise the bringing of new medicines to the market as quickly as possible, and with the minimum of expense." Dalli will answer questions from the members of the European Parliament on 14 January 2010. However, it remains open whether the Parliament will accept a Commissioner with almost all biotech competencies in his hands.
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