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History Lessons
 
Nathan Blow, Ph.D.
Editor-in-Chief, BioTechniques
BioTechniques, Vol. 54, No. 4, April 2013, p. 179
Full Text (PDF)

Another new large-scale biology project is in the offing. The Brain Activity Map (BAM) initiative has gained the support of the Obama administration along with endorsements from several key scientists in recent weeks. However, doubts regarding the feasibility of mapping the human brain have been raised by prominent neuroscientists who argue that the technology to achieve this grand mission is currently lacking.

As supporters and skeptics write perspective articles and blog posts about the potential of the BAM project and government officials figure out a way to fund it, this might be a good time to reflect on past large-scale projects for inspiration and direction. The Human Genome Project (HGP) is considered by many to be the high water mark for large-scale, collaborative efforts in biological research. Mapping the genome took more than a decade at a cost of nearly $3 billion dollars, which is very similar to the BAM time and cost projections. The HGP raced across the finish line in 2001 to great public and scientific fanfare. But how did scientists get to that finish line? It is crucial to insert the name J. Craig Venter here. Venter initiated a privately funded effort to complete a draft sequence of the human genome, employing a different mapping approach than used by the government funded project. That nudge likely led to a more rapid completion of the HGP and the combination of public and private data, produced a better initial reference sequence. In many ways, the HGP was similar to the two-team approach used by physicists in their quest to find the Higgs particle. This highlights the importance of pushing forward with large-scale projects.

Venter approached the genome from a more commercial perspective. Such a viewpoint could be critically important when formulating large-scale biology projects. Involvement of biotechnology and pharmaceutical companies in these projects from the outset, although potentially tricky due to intellectual property issues, adds significantly to the potential future impact. Academics design experiments looking for basic biological insights, while pharmaceutical companies look for direct routes to healthcare applications– both of these approaches are very much needed and should be considered when planning a project the size of BAM.

Another lesson for those scientists working on the BAM initiative can be seen in the recently completed phase of the ENCODE project. This massive effort by hundreds of academic scientists is reshaping how we look at genome structure and function. The amount of data is immense and will fuel discovery for years to come. But the presentation of results in the numerous ENCODE articles published at the end of 2012 also cast a shadow over how the project will be perceived in the coming years. Suggestions by the ENCODE authors that the majority of the genome is ‘functional’ are questionable, perhaps even over reaching, a point raised by non-ENCODE scientists in a number of recent articles. This is the trap of the large-scale project–large volumes of data lead to the desire to make big conclusions. This is not necessary–the data, methods and potential future importance speak for themselves. The HGP and ENCODE provide investigative frameworks and datasets that other researchers can build upon to advance science–empowering generations of scientists is the reason we fund these efforts in the first place.

While the tools needed to complete the BAM might not be in place yet, that should not be a major concern; there are many great methods and instrument developers in the world who will rise to the challenge as others did for the HGP and ENCODE efforts. The potential of the BAM project is extraordinary–a map of brain activity would greatly enhance our understanding of what it is that makes us human. What is worrisome is that we might fail to build on our previous experience to make the impact of the BAM even greater. Project leaders would be well-advised to engage the pharmaceutical community in order to understand what aspects of the project could be directly translated for healthcare benefits. The data from the BAM effort should be presented rapidly and without over interpretation in an attempt to justify the expense and effort. In the end, it is important to realize that the HGP and ENCODE are the great biology initiatives for this generation of scientists–let's make sure BAM reaches its full potential and becomes part of the strong legacy we leave to the next generation of scientists.

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