Interview: Dr. Keith Grimaldi of Eurogene on Nutrigenomics
By Hsien-Hsien Lei, PhD, HUGO Matters Editor
Several years ago, I became acquainted with Dr. Keith Grimaldi who was then Chief Scientist at Sciona, a company offering nutrigenomic tests. Nutrigenomics is the study of the interaction between genetics and diet. Nutrigenomic tests are genetic tests that are used to help people determine the ideal diet for optimizing their health.
Interest in nutrigenomics started around 2003 and peaked in 2005 (around the time I started blogging about genetics). This was the time before direct-to-consumer, personalized genetic testing became the attention-grabbing industry that we are familiar with today which includes tests for specific disease-related genetic mutations to SNP analysis to whole genome sequencing. Nutrigenomics has now claimed a corner of consumer genetic testing and Dr. Grimaldi, who holds a PhD in Clinical Biochemistry from the University of Cambridge, is spearheading the nutrigenomics movement in Europe as Scientific Director of Eurogene, which we’ll learn more about in this interview.
I hope you’ll find this interview enlightening. Dr. Grimaldi has had an interesting career in the field of genetic testing and has much to share. Don’t miss his comments about science and social networking below the fold! If you have any questions for Dr. Grimaldi, please leave a comment.
HUGO Matters: Eurogene is an interesting endeavor in that it’s personal genomic/nutrigenomic testing supported by a consortium of partners. Can you tell us how Eurogene came about and some of the project’s immediate and long-term plans?
Dr. Grimaldi: At the time the project began I was working with Sciona, we had been involved with a number of EU consortium research grants and had also worked for several years with the Biomedical Engineering Laboratory at the National Technical University of Athens (BEL-NTUA) with a group of excellent software and systems developers. A call came out from the EU under the eTEN programme for market validation products. The scope of the call was to use the funds to overcome barriers to market facing new technology products and services that could be useful in society. We put together a small consortium – Sciona, BEL-NTUA, three clinical partners in Italy, Germany and Spain, plus a marketing / business development company from the UK. Fortunately we were one of the chosen few and our project was to use e-technologies to improve the product – to transform the existing largely paper based nutrigenetic test (hardcopy questionnaire and report) into electronic format and develop an interactive website for individuals and practitioners to manage their genetic & personal data and create their own personal reports.
That was the immediate plan but the project evolved along a slightly but significantly different course. It began in January 2008 and phase 1 EU funding saw it through until October 2009. Due to the economic downturn, when Lehman went bust etc, in December 2008 Sciona failed to secure some required funding and had to drastically reduce its operations (and sadly ceased trading a few months later). Sciona left the project and I left Sciona, becoming a member of BEL (it was great, I returned to being an academic and got to be in Athens a lot!). The direction of Eurogene changed then because suddenly it was no longer tied to one product or service – we outsourced genotyping of the remaining patients to a European genetics lab and carried on. One of the interesting findings, in the current debate, was that although Eurogene was set up to deliver both DTC and through practitioners, it was largely the latter market that was more receptive for this type of product/service in Europe and we ended up avoiding DTC. Regarding longer term plans, I think I’ll answer that as part of the reply to the next question
Dr. Grimaldi: As Eurogene was conceived it could have been seen as a sort of competitor to these companies, but it was really complementary. The Eurogene concept is to deliver highly personalised information based on genetics plus diet & lifestyle and other biomarkers such as traditional blood analyses. The aim is to integrate personal genomics with the rest of the person’s lifestyle and health status. We don’t do whole genome scanning or sequencing and restrict the genetic analysis only to those SNPs (and indels, copy number variants, etc) that are relevant for a particular purpose, e.g. a type 2 diabetes (T2DM) profile which we are working on at the moment. The companies you mention do the genotyping and provide quite a lot of interesting information in their reports but it’s not highly personal and is of limited use for clinical decision making. On T2DM for example the information is general, does not quantify, for the individual, the effects of diet, lifestyle, biomarkers and family history on the T2DM risk, nor does it enable personalised treatments, based on all those parameters, to be devised – Eurogene will do all that. A loose analogy could be financial information – if you are a small investor maybe you find enough information for free on Yahoo finance, or with a small subscription to get a bit extra. If you are a serious investor concentrating on a particular sector you will pay a subscription to someone like Reuters or Bloomberg to receive highly specific, detailed information targeted to your sector of interest which will be an important factor in your investment decisions – Eurogene is more like the latter in a healthcare setting (but rather smaller at the moment!).
As the project developed though, the situation has changed subtly, and here come the longer term plans. We are no longer tied to a single commercial genetic test provider and when Sciona left we had to decide whether to continue along the same lines and develop our own tests. We decided not to – there are plenty of genotyping companies out there already and we decided that with the infrastructure and systems that we had developed that our core competency was information interpretation and secure, confidential delivery.
The software tools that we have developed, the Eurogene “Rules Toolset” include several components, the kernel of which is the Modeler – this takes genetic data plus ANY other kind of data (diet, exercise levels, blood analysis markers such as lipids, insulin, glucose, etc) and creates a personal report. The rest of the Toolset includes modules for safe data encryption, transmission and storage; real time generation of updated personal reports managed by the practitioner or customer, through web services, and continual quality control of the algorithms to make sure that the data in is interpreted correctly in the personal report / advice that comes out. The QC module is a very important piece as it also creates a log of all the advice statements created for each report – we think that this sort of exhaustive QC data collection, where we can go back and check what advice / results were given in any particular report from any date will be a key requirement in future regulations (and mistakes can be made – see Daniel Macarthur on decodeme). The system handles information and the end report can be as broad or as specific as needed, it is also interactive so that when you change you diet, or get new blood test results you can create updated personal reports – e.g. it would quantify the risk change for T2DM based on the parameters that change. Of course being an EU project it is also multilingual (the system will also handle Chinese, Japanese, Hebrew, etc), one cool thing about that is that if you happen to require a medical visit while travelling in a different country you can access your account and, with a few clicks, create your personal reports in the local language.
I think you could describe the Eurogene Toolset as a sort of operating system for the application of personal genomics in healthcare, either direct to the consumer or via a practitioner. So now we are even more complementary to 23andme etc. I mentioned above a T2DM model – we are developing this more as a demonstration than as a product – it will allow anyone who already has their results to register with the website (anonymously), input their genetic data plus other personal information (diet, biomarkers, etc) and produce a personal report based on all the elements, not just the genetics. The system can handle all sorts of complexity, I have always been closely involved with NuGO (in fact we held our 2nd workshop at Nugoweek in Italy last year) and we have made sure that the Rules Toolset will be compatible with all the “omics” data once that begins to have clinical applicability.
So longer term…we are a small consortium and the phase 1 funding is over. We are now deciding whether to pursue private funding (we have created a business plan) or whether to look for more public funding, both have their pros and cons. But as we are very clear about what we are and we expect to work with other companies who have, or want to develop, personal healthcare services for which we would provide all of the infrastructure and systems for interpreting data and delivering services. It allows each partner to concentrate on its expertise, we have built a complex set up that would cost several €100,000s and a couple of years to reproduce and we will make it available to companies who want to deliver their expertise through healthcare personal services.
HUGO Matters: What are the major challenges facing the field of nutrigenomics?
Dr. Grimaldi: Although in Eurogene we are moving away from a strictly nutrigenomics field to more broadly cover personal genomics the challenges are similar, and familiar:
Regulations – we need some framework and we need it sooner rather than later. At Eurogene we researched this quite a lot (a review will be submitted for publication soon) and there is basically no real regulation of any sort anywhere except in some isolated cases like the recent German legislation. Even with the strict (widely criticised) German legislation it’s hard to see how it will stop DTC sales into the country over the internet. Our position is that we strongly support self-regulation as I describe in more detail on my blog and the main reasons are time and flexibility – we would be happy to work with any government regulation but that will take too long and will probably be obsolete by the time it comes into force. Look at the reports from the recent #AGBT Conference, sequencing cost is tumbling – what will it be like in 3-5 years time? Our longer term view at Eurogene is that soon there will be so many people with their own DNA results that it will no longer be necessary to offer genotyping to start up a personal genomics company. All you will need is a website and an internet connection to start selling interpretation services – can you imagine the free for all that will happen? Even now with the significant start up costs there have still been some very dubious companies appearing over the last few years, imagine what it will be like when the start up costs will be low. Actually they will be low to start up a poor service, the costs will still be high to provide a real service, providing personal healthcare information and interpreting results is not cheap or easy if it is done properly, but is if it is done badly. We urgently need some movement on self-regulation so that the public (and professionals) will be able to identify who are the credible companies; we need it for the protection of ALL the stakeholders (except the scam companies).
Credibility – this is essential of course but we have all taken hits over the years plus anything involving nutrition is vulnerable. We have to be open and transparent; the companies mentioned above are very transparent but there are several unmentioned who are not. We all have to be careful about our marketing and claims. Episodes like the recent press release of a conference presentation of a trial to support a weight management genetic test does not help. The test may or may not be valid, but weight loss is such an exploited area that much more care is needed and I don’t agree with press releasing a conference presentation to claim scientific validity to help sell a test, any test let alone a genetic test. Until the data are available for scrutiny either online or written up and published then there is no basis for using them as support for sales – I know it goes on all the time in the supplement industry but maybe that’s precisely the point, personal genomics and especially nutrigenomics has to be a long way from the level of the supplement industry – the bar is much higher, maybe artificially higher because of the G-word, but that’s the reality we have to live with.
These are the two main barriers I think – there are many others, e.g. reaching levels where there is undisputed clinical utility & demonstrating it, educating healthcare professionals and providing them with the tools to integrate genomics, to name a couple, but without overcoming the main barriers any long term growth will be painful.
HUGO Matters: Once whole genome sequencing becomes affordable and efficient, how do you think the field of nutrigenomics will change?
Dr. Grimaldi: OK I think I partly answered that above, I will add that I think it will have an enormous effect. At the moment genotyping is tied to a particular service, all that will change, (in fact you could say it has already started, if you remember, a few months ago deCODE offered to interpret 23andme customer data free of charge). Personal interpretation services will cost much less and results will be delivered in real time – instead of waiting a few weeks for your sample to be processed you can just upload you data and get your report immediately (at least if you use the Eurogene system…!). Two barriers fall in one go: time and cost. Plus I think there will be enormous opportunities for research using customers and patients – somewhat like 23andme have been trying to do with their customers, but in a more controlled healthcare setting. When there will be hundreds of thousands, millions, of people with genetic data linked to other biomedical-physical data it will be like the UK biobank initiative multiplied many-fold. Eurogene has anticipated the future here with systems for anonymous and confidential databasing of genetics plus biomarker records, we are also working with information research groups on developing artificial intelligence systems that will be required to analyse and interpret the data (see for example Valavanis et al, 2008) – we have got as far as actually using a neural network component in the report generation, online and in real time, it’s rudimentary but it proves the concept)
HUGO Matters: You’ve recently joined the blogosphere and become active on Twitter. How has your experience been and how has social networking changed the way you feel about and do science?
Dr. Grimaldi: It has been nothing less than a fantastic experience and much more rewarding than I had expected. I have been reading and following for many years (as you know!) but my plunge was prompted by the Eurogene EU project officer. An important activity for any EU project is dissemination and he suggested blogs etc – I took a few months before jumping, afraid that I would not be able to keep up with the pace, but it has been so useful. Blogs are straightforward – scientists write articles, we read them and we can fairly soon decide who is worth following. I was more dubious about Twitter mainly through ignorance and lack of understanding but it has proved to be one of those “how did I get on without it” things. I have learnt of so many research studies through Twitter and of course it was extremely useful for telling people about the Eurogene blog (I got over 100 people on the first day, I have no clue if that is good or not, but it was much more than I expected).
I will show my age here, when I was doing my PhD keeping up with the literature involved a leisurely afternoon at the library browsing the main journals and thumbing through Current Contents – all changed now and the social network tools have become invaluable. I am really impressed at the levels of collaboration and everybody is there helping each other – luminaries from industry, ace scientists, scientific journalists, teachers, students, and the simply interested. One hope I have is that it will help us all sort out the problems of what is credible and what is not in the commercial personal genomics world where ignorance is such a threat. I wish it had been around at this level when Sciona began back in 2001 (I joined in 2002) – we were attacked a lot but there was a lot of ignorance displayed (I don’t mean general ignorance, I mean it in the sense that comments were often prejudiced and uninformed) it was difficult to defend against. Over the years we always found that people who got to know us were generally positive (hence the many friends in NuGO and people like Jose Ordovas and Wally Gilbert on our science advisory board, plus being able to convince investors like BASF and DSM). If the social networks had existed to the extent that they do now I think we would have had an easier time defending ourselves and describing what we really do (I do remember posting to your first genetics blog – that was actually very helpful). But it’s there now and I’m very happy for that because it will really help the good companies survive and it is already illuminating to see who actively participates and who doesn’t.
You can find Dr. Keith Grimaldi at the Eurogene blog and on Twitter @eurogene. The Eurogene blog is also a member of The DNA Network, a collective of blogs about genetics and genomics that I co-founded.
*NPR, 26 Dec 2003