Since Prof. Leroy Hood (ISB, Seattle, USA) first proposed the concept of P4 medicine (predictive, personalized, preventive and participatory), some of his vision has already become reality, and the technological developments that he so avidly champions, has also seen rapid progress. The most notable result of these changes is perhaps the significant drop in the costs associated with whole genome sequencing. The technology has not only enabled many novel findings, but has also raised new social and ethical challenges. It is the goal of the first EMBL conference on “Omics and Personalized Medicine”, jointly organized by Rudi Balling (LCSB, Luxembourg), Leroy Hood, Wolfgang Huber (EMBL, Heidelberg, Germany) and Lars Steinmetz (EMBL), to address the potential and challenges of translating systems biology research into the clinic by “bringing together scientists and clinicians”, according to Dr. Steinmetz in his opening speech.
The first EMBL conference on “Omics and Personalized Medicine”, jointly organized by Rudi Balling (LCSB, Luxembourg), Leroy Hood, Wolfgang Huber (EMBL, Heidelberg, Germany) and Lars Steinmetz (EMBL) addresses the potential and challenges of translating systems biology research into the clinic. This meeting report provides a highlight of the conference, covering not only the science, but also social and legal issues.
The EMBO Lecture
Prof. Leroy Hood opened the conference with “The EMBO Lecture” – Systems Approaches to Disease and the Emergence of Proactive P4 Medicine. According to Prof. Hood, progress in P4 medicine over the next decade will generate billions of data points for each individual, and the grand challenge would be how to integrate the information. A crucial point of this is the signal-to-noise ratio of high-throughput data. Using his group's study on prion disease  as an example, Prof. Hood demonstrated how the background noise in biological data can be removed through a systems approach. The group studied multiple parameters in eight strains of mice over time – the use of different strains of mice allowed them to separate what is a strain-specific phenomenon to the “real” changes in gene expression as a result of prion disease. Not only did Prof. Hood talk about a systems approach to medicine, he also gave his presentation with a systems approach – the whole process from bench to bedside was discussed, including what we could do as individuals to make the choice of being proactive about our health, as exemplified by Prof. Hood's reference to Prof. Larry Smarr's efforts to quantify his own body.
Omics and cancer
As mentioned in the report to another meeting that I also attended recently , cancer is a leading cause of death around the world and has been the major driving force behind the efforts of many research laboratories; cancer was also a major theme at the current conference. Some examples included Dr. Jan Korbel (EMBL)'s presentation on childhood medulloblastoma, in which he discussed a new mechanism of tumour development, i.e. “chromothripsis” [3, 4]. Also on pediatric brain tumours, Prof. Peter Lichter (DKFZ, Heidelberg, Germany) presented their work on integrated (i.e. integrating whole genome, whole exome and RNA sequencing, methylome analysis) approaches to identify mechanism underlying medulloblastoma tumorigeneisis. Also with an integrated approach, Prof. Anne-Lise Bo̊rresen-Dale (Oslo University Hospital, Norway) discussed personalized treatment of breast cancer, in which predictive prognostic markers were identified. Interestingly, one of the pathways perturbed in breast cancer was that of the immune system, and better prognosis was associated with a type 1 immune signature (see [5–6] for further reading on cancer and the immune system).
While understanding disease mechanism is important, it is also critical that the knowledge is translated into medical practice. In this direction, Dr. John Castle (TRON, Mainz, Germany) presented data on exploiting the cancer mutanome to identify cancer-specific targets for immunotherapy with polytope vaccines.
Data overflow – what to do with it?
A clear challenge to the medical science community is the shear amount of data generated by high-throughput studies. Prof. Sven Bergmann (University of Lausanne, Switzerland) presented their work on the “Cohorte Lausannoise”, a random population sample of 6000 or so individuals who were genotyped for 500000 single nucleotide polymorphisms (SNPs). The group attempted to correlate this information with phenotypes, and identified 20 loci associated with adult height .
Genomic information alone is complex, further adding to the complexity is the interaction between genes, between genes and the environment, and the outcome of these interactions. Using the Zeebrugge ferry disaster as an example, in which multiple factors finally led to disaster, Prof. Cornelia van Duijn (Erasmus Medical Center, The Netherlands) vividly presented her case that perhaps genome-wide association studies may not have such a powerful predictive function and the major challenge is to determine which of the current complex diseases can be accurately predicted with personal genome testing. Also pertaining to dissecting complex interactions, Dr. Wolfgang Huber and Prof. Michael Boutros (DKFZ) each presented their collaboration on high-throughput combinatorial RNAi effects on cell culture combined with automated image analysis. The groups use such model systems, together with mathematical modeling to examine complex molecular interactions .
Omics approaches and “other” diseases
While much emphasis was placed on cancer, and rightfully so, cancer is not the only disease where systems approaches have yielded powerful insights. At this meeting, several presenters demonstrated how genomics approaches can be used to understand “other” diseases, such as Prof. Stylianos Antonarakis (University of Geneva, Switzerland)'s presentation on Down's syndrome. Dr. Peer Bork (EMBL) presented his group's work on the human gut microbiome and suggested a potential value in diagnostic biomarker discovery . Dr. Lars Steinmetz (EMBL) discussed their work using yeast as a model organism to study mitochondria defects and identify potential therapeutic targets .
Ethics and legal issues
As with many new technological breakthroughs, our ability to read into the information stored in our genomic sequence has led to ethical debates and legal concerns. At this meeting, the ethics and legal issues were discussed by two experts, namely Dr. Anne Cambon-Thomsen (Inserm, France) and Prof. Hank Greely (Stanford University, USA), respectively.
Prof. Hank Greely presented his perspectives from a legal point of view. One important and very real concern is that of patent law, through which information and data may be locked up and prevented from public use – he therefore recommended a “wiki” model, in which qualified experts are able to contribute to and edit the information, as well as commenting on existing information available. Another complication is where should the information be stored? At the doctor's office? A central database? Who would have access to this information and how can our legal system prevent this from abuse? Adding to this is the attitude of patients – due to various cultural and historical reasons, the general attitude of patients varies from country to country, and it is important that we convince everyone of the value of participation.
Dr. Anne Cambon-Thomsen presented the results from patient study groups. There are two main facets of “personomics” (i.e. not only genomic but all omic information), the obvious one is that of improved medical care; however, this also comes with anxiety for potential genetic discrimination. Amongst the participants of the study, there was a general perception that technical developments are inevitable, although most felt positive about these changes. There were also concerns with regards to how the healthcare system will be able to manage the information and whether we have the moral and political ability to face the complexities, for example, should one disclose “problematic” results that have no medical solutions? Understanding patients' attitudes is of great importantance, for example, one conclusion from the study was that avoiding hype is key to building trust – something that all involved in the process have a vested interest in.
Panel discussion: Bringing the meeting into perspective
The panel discussion, a final highlight of the meeting, was chaired by Prof. Rudi Balling and consisted of the following panelists: Prof. Leroy Hood, Prof. Hank Greely, Dr. Robert Gentleman (Genentech), Dr. Tim Hubbard (Wellcome Trust Sanger Institute, UK) and Dr. John Overington (EBI, UK). In his typical humourous and good-natured fashion, Prof. Balling brought several tough themes to the panelists as well as the audience, including how to work together and achieve truly inter-disciplinary science, how to gain public support and understanding, and most importantly, how to move forward and achieve the vision of P4 medicine.
When it came to how to work together, there were many divergent opinions. Tim Hubbard for example, endorsed a government-driven model and championed the idea that it is all about consortia design and it is the funders who should be “whipping” the consortia into shape to deliver results. Others, such as Hank Greely, took a more inter-personal perspective and stated that it is about talking to people and showing interest. While Lee Hood preferred a combination approach of creating the infrastructure that allow for people to communicate.
A lack of understanding, or even worse, misunderstandings, can lead to mistrust. Learning from the experience of the early days of the human genome project, the panel agreed upon the importance of communicating scientific results and gaining public support for their research. To open this part of the discussion, Prof. Balling asked the rhetorical question, “are politicians special”. For me personally, the comments from Hank Greely resonated most, because, as he stated, politicians are driven by their electorates, which in turn receive their information from popular media. It is therefore important that scientists should make an effort to engage and educate scientific journalists, who are much more effective at communicating scientific discoveries to the general public.
And finally, how do we move forward and achieve effective healthcare? Education appears to be key: Lee Hood has already worked with high schools in the US to incorporate small modules of systems biology into their curricula; the importance of education in mathematics is also emphasized, especially, as Tim Hubbard mentioned, with the increasing outsourcing of experimental work, it is the ability to analyze and make sense of the information that is the most valued skill.
The first “Omics and Personalized Medicine” conference, hosted by EMBL, took place over three days – but time, as they say, flies when one is having fun, and the conference felt as if it were much shorter. Due to space limitations, it was impossible to describe each and every presentation, but I hope that this report has provided an accurate flavour of the diversity of the conference and will motivate even more researchers to take part in the next gathering.
Judy Peng, PhD., Managing Editor, Biotechnology Journal
I would like to acknowledge the support from Dr. Lars Steinmetz and Nicola Vegiopoulos from EMBL for their help in putting together this meeting report.