Billion-Dollar Brain Map

A proposed effort to map the activity of the human brain is being compared to the Human Genome Project.

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It appears that the push of

It appears that the push of NIH Director Dr. Francis Collin and a few others to convince the US government to commit to multi-billion dollar funding of the Brain Activity Map will be paying off. However, this may ultimately provide even less practical and poorer economic returns than the formal Human Genome Project that Dr. Collin's championed and led in the US.

There is no doubt that there is a great unmet need to better prevent, diagnosis and treat Alzheimer's disease, Parkinsons' disease, multiple sclerosis, schizophrenia and many other devastating neurological disorders, and this requires increased research and development funding from government, charities and industry. However, I really seriously question the wisdom of diversion of a significant amount of limited resources available at this juncture for basic scientific research towards the specific goal of mapping brain activity patterns at the cellular level, similar to the Human Connectome Project that Dr. Collin praised in his blog last year in November (http://directorsblog.nih.gov/the-symphony-inside-your-brain/). A more complete description of the Brain Activity Map proposal in a white paper can be downloaded from Columbia University Academic Commons (http://academiccommons.columbia.edu/item/ac:147966).

In the Brain Activity Map proposal, entitled “The Whole Brain Activity Map: Merging Nanoscience and Neuroscience for Technology and Health” and dated in 2011, the proponents ultimately seek to determine how the brain computes by creation of a detailed anatomical highway map of the brain. While the four and a half page paper is obviously short on specifics, it initially describes expanded studies of the brains of the worm C. elegans, the fruit fly Drosophila and the mouse to map out individual neuron interactions. However, the longer term vision encompassed by the proposal is both fanciful and actually quite frightening. It states:

“Beyond these immediate next steps, we envision working towards the ultimate development of subsequent generations of untethered, nanoscale neural probes that can locally acquire, process, and store accumulated data, and that would ultimately be configurable into a communications network within the tissue. Such device networks could potentially address the long-standing problem of how to obtain sufficient coverage in deep tissue layers. These networks of “intelligent” nanosystems would also be capable of providing specific responses to externally applied signals, or to their own readings of brain activity. Their responses could be used to trigger nerve cell activity in a measured manner, and could comprise the first steps in controlled restoration of normal patterns of activity in damaged brains. This would initially be done in animal models for brain injuries, such as TBI and PTSD, or for psychiatric disease.”

There is a huge litany of issues ranging from technical, economic, and practical to profound ethical considerations associated with such a proposal. The “mind blowing” implications that human brain activities such as perhaps the generation of thought itself might become directly controlled by mechanical intervention that could be inputted by others or even artificial intelligence raises the deepest of concerns. Every major advancement of science and technology comes with consequences that are not necessarily in the best interests of most of humanity or the rest of our planet. Much more extensive discussions amongst brain researchers and ultimately the broader community internationally is warranted before significant amounts of funding should be earmarked for such a project.

One of my chief concerns are that fruitful research along different lines, such as the promising use of stem cell technology or molecular pharmacology, to treat neurological disorders, will be compromised with a major effort that is fixated on mapping neuronal connections that in the end may not really be able to rectify the pathological processes that underlie the most common brain and spinal cord diseases. In the vast majority of these illnesses, it is the destruction of neurons and other supporting brain cells that leads to loss of brain function. Neuroscience researchers will be diverted from engaging in more timely and practical directions as they will be forced to follow the money if they wish to receive any significant financial support.

My other primary concern relates to the plasticity of the human brain itself. While each muscle in the human body is ultimately controlled by a single neuron, and the brain is organized into distinct subregions linked with particular motor control and cognitive functions, there does not appear to be a requirement of specific neuronal interactions at the cellular level. The number of neural connections in the adult human brain is in the order of 100 to 500 trillion. Each neuron has on average about a thousand direct links to the synapses of other neurons. The true value of mapping this to such a high level of precision is dubious and only a generalized map can be produced ultimately. Vast variations with the individual differences in the connectivities of nervous systems amongst people will significantly undermine the value of any generalized map. Such differences arise, because personal genomics and different environments have a huge impact on brain development and fine structure. As a very plastic organ, whole regions of the brain can wane and expand depending on, for example, the sensory inputs, nutrition and exposure to toxic substances.

While I really applaud the efforts of scientists to carefully investigate the architecture of the brain down to the level of intercellular connections and deeper, the challenges, fruits and risks of multi-billion dollar programs such as the Human Genome Project and now the Brain Activity Map require much deeper scrutiny. It seems to me that the objective of deducing the connections of all of the neuronal connections is like trying to identify all of the types and placements of trees, shrubs and plants in a vast forest. There are clearly underlying principles at work that influence the general composition and arrangement of the vegetation in a forest and how it functions as an ecosystem. However, when you view more forests over the surface of the planet, it is clear that no two forests are the same despite their initial similarities when viewed from 30,000 feet above. I believe such an analogy applies to the proposal to map the human brain at the single cell level. It seems to be a rather “ill conceived” project.

Dr. Steven Pelech
Professor
Division of Neurology
University of British Columbia