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Open science for open mind

September 11, 2013

I have been working on neurobiological research for more than 15 years since I graduated from medical school. The first field in neuroscience attracted me is neural stem cells, then the neurodevelopment, and I saw the many breakthroughs happening in the past 15 years in understanding the pathogenesis of neurological diseases and normal cortical development. What Raymond Kurzweil described in his book ‘Singularity is Near”, that an exponential increase in technologies like computers and genetics is somehow true. During my study of Alzheimer’s disease and Down syndrome in the past 15 years, I saw the finish of human genome project, broad applications of high throughput sequencing technology, new frontiers of bioinformatics, epigenetics and induced pluripotent stem (iPS) cells, genome-wide association study (GWAS) to identify susceptible locus for depression and schizophrenia. I used these new technologies myself, including high throughput DNA methylation profiling and iPS cells to discover new pathways in Alzheimer’s disease and Down syndrome, which is unthinkable when PCR is still a new technique when I studied in medical school. I believe all these advances are unachievable without open science approaches.

When I prepared my master thesis 15 years ago, I had to go to libraries to get literature prints using copy machines, and prepared thesis defense slides using developed films. That is the start of my science career though watching copy machine working and staying in darkrooms for film development had not much fun. Nowadays, with one computer connected to internet, I can find almost all the resources and solutions to my questions and technique problems, from the open access to papers, protocols, methods, software, discussions, webinars, and Google becomes the most often used tool instead libraries. With the exponential increase of publications, you can imagine how much time it saves for you to keep you in the frontier of your research field.

The open science approaches not only include the free access to scientific publication like what NIH is doing in PubMed central, but also all other scientific resources that are shared by all the research community. In a recent project on Down syndrome study, we want to study a gene on chromosome 21, which has an extra copy in Down syndrome patients. To examine the gene expression in the Down syndrome brain, we got invaluable frozen brain tissue of specific ages from Brain Bank at National Institute of Child Health and Human Development (NICHD) in Maryland, who had collected thousands of brain samples from different neurological disorders. To manipulate this gene, we got this gene bacterial clone from BACPACResourceCenter” (BPRC) located at the Children’s Hospital Oakland, California. To target this gene in iPS cells, we got transcription activator-like (TAL) effectors nuclease (TALEN) constructs from Addgene contributed by Jung lab in Massachusetts general hospital (MGH), and Down syndrome iPS cells from Harvard Stem cell Institute in Boston. At last, to study the gene in animal models, we got the DS transgenic mice from Jackson Lab in Bar Harbor. With these tools, we can test our hypothesis in 1-2 years; without these resources, it could take years or decades to achieve our goal to find out the gene function in this disorder.

Above is a simple example from my research experience. In addition to this convenience brought by open science approaches, with more people involved, it may facilitate the improvement of quality, education and application of science to benefit the society. Moreover, current challenges are mainly from the increasing data in high throughput screens of genome or epigenome and imaging or electrological recording in normal and diseased people. One single person or organization cannot fulfill these data mining and interpretation work; it has to be a well-coordinated maneuver of many teams and groups. Many institutions and companies have begun to develop integration platforms from these data, such as ExPASy, NEXTBIO, SAGE and the Human Connectome Project, and the open accessibility of the data is essential to achieve the final goal. This open platform for the open mind ensures everyone with curiosity can think about it and contribute their ideas; they can download the data freely to analyze them with their own mathematical models; they can discuss the projects freely with professional or nonprofessional scientists. I believe these efforts will accelerate our understanding of the physiological and pathological mechanisms of human development and diseases, and find more pharmaceutical interferences for curing these diseases.

The open access to scientific resources has changed our view of traditional research. In a time of self-education with free access to information, knowledge and known techniques, it will stimulate more innovative thoughts without restrains. The most important thing is how to use this free information to produce new ideas and techniques. With this knowledge, we could avoid the known knowns and known unknowns to focus on the unknown unknowns, which are the real gold mine of scientific discovery.

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