Delving Deeper into DNA

Dr. Patrice Milos, Vice President and Chief Scientific Officer of Helicos BioSciences explains her new role, the innovative new technology she works with and her vision for the future of DNA and RNA.

NGP. You recently joined Helicos as the company's CSO – can you briefly describe your background and experience in the pharmaceutical industry?
PM. I joined Pfizer’s Molecular Sciences department in 1993 to integrate new genomic technologies into the study of cardiovascular and metabolic diseases. I worked with other scientists to identify new therapeutic approaches to treat disease and was fortunate to work with many therapeutic area programs. By 1996, I was excited about what was happening in the field of human genetics, given all the technology breakthroughs. We made the strategic decision to start the Pharmacogenomics group at a really dynamic time for Pfizer.

Over the next 10 years, Pfizer grew to be the number one pharma company in the world and developing the Pharmacogenomics group during this time was a truly unique and exciting experience for me. It allowed me to find my true passion – bringing the science of genomics closer to the patient. Finally in 2005, we created the Molecular Profiling Department in Clinical Development where we essentially moved basic research closer to the patient.

NGP. Could you give me some background information about your company?
PM. At Helicos we are focused on developing innovative genetic analysis technologies for the research, drug discovery and clinical diagnostics markets. We are very excited about our first commercial product, the HeliScope™, which is based on our proprietary True Single Molecule Sequencing (tSMS™) technology. Our technology will provide researchers the ability to rapidly analyze large quantities of genetic material by directly sequencing single molecules of DNA or single copies of RNA. It’s really the first comprehensive, universal solution for single molecule genetic analysis and what’s really important is that we have the potential to dramatically lower the cost of individual genomic analyses for our customer. By driving costs down and working at the single molecule level our platform should enable science on an unprecedented scale and really move the field of translational research closer for scientists, clinicians and patients. I believe that my passion for personalized medicine can become a reality and that Helicos BioSciences will play an important role in enabling others to pursue the critical research directed at improving medicines. Also, as we learn more and more about the genetic basis of common disease, our platform becomes equally important for molecular diagnostics in those diseases where genetics plays such a key role. You can imagine this in cancer, cardiovascular disease, CNS disorders just to name a few.

NGP. What attracted you to Helicos’ technology and how will it help the drug development process?
PM. While at Pfizer I knew that to truly achieve a personal goal of mine, the realization of personalized medicine, we needed to go deeper into the DNA – at the individual DNA sequence level. At the same time, I recognized that I had a limited view of the personalized medicine field as I was only seeing it through the eye of Pfizer. I recognized my need to reach outside of the world of pharma, but I wasn’t quite sure how to do it – until Stan Lapidus, CEO of Helicos, called and discussed Helicos’s remarkably novel approach to single molecule DNA sequencing.

Helicos is in the unique position of possessing a technology platform that has the potential to revolutionize the ability to integrate all aspects of genomics into the pursuit of new medicines – from early discovery work right through into the commercial marketplace. Questions that I couldn’t answer about drug response and toxicity could now be researched at the individual patient level. With the HeliScope we will be able to interrogate quantitative RNA changes, DNA sequence information, DNA methylation status – all through single molecule detection.

NGP. How is this different from other technologies?
PM. Helicos is the only company that can obtain genomic information at the single molecule level, which means we analyze individual molecules of DNA directly instead of analyzing a large number of copies of DNA produced through complex sample preparation. Not only does this make the lab work easier for the user, it also allows researchers to get closer to the real biology by preventing the introduction of errors and bias resulting from amplification. It really gives scientists a major new platform with a wide range of potential applications to do “big science” given the throughput, simplicity and cost per sample.

NGP. What is Genomic Signature Sequencing and what impact does it have?
PM. Genomic researchers have invested significant resources, over the last several years, to develop transcriptional signature profiles of various biological samples – cell lines, disease tissues, tumour tissues and so forth. The ability to interrogate these signature profiles in a very high throughput and reproducible manner has been limited, yet that’s exactly what we need if we hope to understand how to perturb this signature and build our understanding of how to treat disease. With Genomic Signature Sequencing (GSS), researchers will be able to measure the expression of subsets of genes across tens of thousands of samples at a cost lower than any other RNA methods. I envision pharma using quantitative RNA measurements in cell-based assays, across very large numbers of compounds, to measure tens to thousands of genes. This should allow the high throughput screening groups to discover new molecules, which alter disease or biological pathways. The GSS application also allows the researcher to customize the biological gene expression pathway or signature they’re interested in and this has important implications for clinical research. Often the array based methods work quite well in discovery of the gene signature profile but when you move this signature into the clinic where you need a highly quantitative assay with high sensitivity and specificity, the options for such measurements have been very limited and very expensive given the large numbers of samples you analyze in clinical trials. GSS should give translational researchers the tool to interrogate their RNA signature profile. You could imagine studying your signature in thousands of clinical samples for making real decisions. Imagine being able to apply a particular gene signature of 100 or even 1000 genes in early clinical testing of novel compounds and mechanisms. When you look at RNA expression changes seen in such clinical studies you could open new insights into pathways perturbed by a pharma’s exploratory molecule and provide potential new indications for your new mechanism or molecule.

NGP. What other applications are you working on?
PM. There are many applications that we are currently working on for the HeliScope. The scientific community is very excited about our true single molecule approach to DNA sequencing for both candidate genes and genomic regions, as well as for sequencing of whole organisms. Digital gene expression is another important ongoing application where we believe Helicos will have a major competitive advantage. Given that we do not require PCR amplification, we aim to ensure little if any bias is introduced by our sample preparation methods to allow researchers to really delve deep into the RNA molecules present in any sample of interest with a very broad dynamic range to allow detection of rare transcripts and accurate quantitation of highly abundant RNA species. We are also developing our collaboration portfolio for exploring the new scientific areas in which the HeliScope could be used to explore basic research questions to unravel the biology of the genome. Our goal is to explore multiple new aspects of DNA and RNA research to better understand how the HeliScope can be used and this includes discussions with potential collaborators on methylation, chromatin interaction studies, miRNA research and even the potential for diagnostic applications.

Dr. Milos joined Helicos in June 2007. Her expertise and extensive knowledge in the life sciences advances the company's efforts to develop innovative and breakthrough technology. She previously served as Executive Director at Pfizer Global Research and Development, where she was responsible for leadership, strategic alignment and execution of the scientific disciplines of pharmacogenomics, proteomics, metabonomics and RNA profiling across the Pfizer portfolio from early discovery into the marketplace. She joined Pfizer in 1993 and held numerous research positions of increasing responsibility focusing on Cardiovascular and Metabolic Disease, Pharmacogenomics, DNA Sequencing, Biomarkers and Molecular Science.

Dr. Milos serves on the National Advisory Council for Human Genome Research and was pivotal in the establishment and oversight of key Pfizer strategic investments in the genomics area, most notably, the Genetic Association Information Network. She also sits on several editorial boards for journals and has published and presented extensively in the genomics area. Dr. Milos conducted post-doctoral fellowships at Brown University and Harvard University. She earned her MS and PhD degrees at Rensselear Polytechnic Institute in Troy, NY and received her BA from The College of Saint Rose in Albany, NY.