A huge neuroscience project is just getting started: will you be a part of it?
When you think of the largest government undertakings that had the largest impact in the modern era, what comes to mind? (By ‘impact’ you can consider the economic, social, or scientific ramifications excluding war, which of course is a separate question.)
First (and most recent) is the Apollo Moon Project. According to historians it was driven more by global politics rather than scientific discovery, cost some $24B USD in 1973 dollars (equivalent to $170B USD in 2005) but as far as a large, ambitious government projects that made great progress as a society it is difficult to argue against.
Second (and perhaps controversial) is the Manhattan Project, resulting in the atomic bombs of World War II. Employing at one point over 130,000 people with an estimated project cost of $2B USD in 1946 dollars (estimated cost of $26B USD in 2014), the “Atomic Age” was ushered in, a marker for a modern era but not without a range of social problems to accompany it, both from the threat of nuclear warfare as well as the adoption of nuclear power.
A third major government project with a large impact was started in 1881 by the government of France, later taken up by the United States in 1903: the Panama Canal. At a cost of $639M USD in 1914 dollars (estimated cost of $14B USD in 2007), the canal saved 7,800 miles (12,500 km) of travel, reducing a 13,000 mile (21,000 km) trip from New York to San Francisco to about 5,000 miles (8,000 km). At the time it opened in 1914, a journey that used to take 60 days was reduced by half due to the canal, and ‘lived in the public’s imagination unlike any other event of recent memory’. Its commercial impact was recognized immediately, and currently the Panama Canal generates over $2B USD in user-fees every year. A $5.2B USD effort is currently underway to double the Canal’s capacity by 2016.
We now naturally come to the Human Genome Project. Officially launched in 1990 with a five-year plan for what was projected to be a 15-year project, its goals included the mapping and sequencing of E. coli, S. cerevisiae, C. elegans, D. melanogaster, and M. musculus on the way ultimately to H. sapiens. The budget for this project, $3.8B USD (estimated to be $5.6B USD in 2010), was estimated to return an economic benefit of 141-fold to the US economy a decade after its completion in 2003.
The impact of the first three historical events are achievements with defined boundaries and limitations. The last human visit to the moon was Apollo 17, December 7 1972 over 42 years ago. Some proposals have been made for human spaceflight to Mars, and at present there is ongoing travel and research in near-earth orbits on the International Space Station, but the future of manned spaceflight is unclear at present. For the future of nuclear power, the recent Fukushima disaster and lingering containment concerns at Chernobyl put the future use of nuclear energy into question. And for the growth of worldwide maritime commerce, expanding both the Panama and Suez Canals is currently underway.
The argument can be made that the Human Genome Project which mapped and sequenced five model organisms along with the human species, stands alone in its potential. As a ten-year anniversary of the Human Genome Project editorial stated in 2011, the ‘best is yet to come’ regarding the scientific and medical promise of this milestone. The editorial went on to state that the human genome project was ‘in many ways a triumph for technology as much as it was for science’. The improving sequencing technology, and the importance of all the other necessary accompaniments (sample preparation, reagents, bioinformatics, etc.) for the success of an undertaking of this magnitude are laid out in another editorial in the same 2011 journal (“A decade’s perspective on DNA sequencing technology”).
It is hard to imagine what a bold step it took in 1990 to lay out a 15-year program for sequencing the entire human genome, when at the time the technology to do so simply did not exist. And yet the step-wise investment into a project that spans over a decade, involving thousands of individuals, is on a scale that only a government program can organize and achieve.
In April 2013 a similarly bold step was taken when the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative was announced by the US Government. The long-term scientific plan was laid out recently in June 2014 titled ‘BRAIN 2025: A Scientific Vision’, which identified 7 high-priority research areas and called for a 12-year commitment and $4.5B USD in funding.
The BRAIN Initiative launched in 2013 with $100M USD in initial funding (fiscal year 2014) from the National Institutes of Health (NIH), the Defense Advanced Research Projects Agency (DARPA), and the National Science Foundation (NSF). In addition, private institutes such as The Allen Institute for Brain Science (Seattle WA), the Howard Hughes Medical Institute (Chevy Chase, MD) and The Salk Institute (La Jolla CA) have committed to support related activities on the order of another $120M USD annually.
This project seeks to unravel how the human brain’s 86 billion neurons and trillions of connections interact in real time. The technology to study neural circuitry in vivo is in its infancy; although transformative technologies such as optogenetics are being fully leveraged in neuroscience, many more breakthrough and revolutionary technologies are needed. Interdisciplinary development for brain imaging, analyzing (and being able to modulate) groups of cells that work as circuits, development of recording devices to record inter-neuron communication are just a subset of the kinds of new tools that need to be invented.
At the recent Society for Neuroscience meeting in Washington DC, there was interest in the Arcturus® Laser Capture Microdissection System of the University of Connecticut Health Center who uses a combination of the Arcturus® LCM and the Applied Biosystems® 7900HT Real-Time PCR System with focused-set TaqMan® Mouse Immune Array Cards to look at brain vasculature to understand the blood-brain barrier. Dr. Pachter points out that only the Arcturus® LCM System has a proprietary dual-laser system, in particular a gentle infrared laser ideal for capturing single-cells or low numbers of cells. This ‘soft laser’ is also highlighted in Dr. Chip Petricoin’s LabChat video.
Another aspect of the Arcturus® LCM System that makes it ideal for neuroscience research is the availability of a wide-slide stage insert to enable microdissection of much larger tissue slices.
The BRAIN Initiative will tackle among other neurological diseases Parkinson’s disease. Thermo Fisher Scientific has been collaborating with leading Parkinson’s disease researchers, and three articles about ‘Modeling Neurodegenerative Disease‘ are available. The papers are titled ‘Generation of induced-Pleuripotent Stem Cells’, ‘Generation of Neural Stem Cells’ and ‘Editing the Genome’, and were produced in collaboration with the Parkinson’s Institute. (The biographies of the scientists involved in this work are available here, and so is Dr. Birgitt Schuele’s ISSCR 2013 presentation on generating Parkinson’s Disease models from iPSCs.)
If you are currently working with single-cell or low cell-number analysis using laser-capture microdissection and would like to collaborate with us, feel free to contact us directly.
Do you have some interesting technology you are developing as part of this BRAIN Initiative? Will you be applying for direct or related grants? Let us know in the comments.