CONNECTOMICS

THE FUTURE OF PERSONALIZED MEDICINE

By SHAYNA COHEN YIFAN MAO

In 1990, the U.S. Federal Government embarked on a billion-dollar journey to do what was once thought impossible: sequence the human genome. With the ambitious goal of identifying genetic variants involved in diseases like cancer and diabetes, researchers quickly began their work on the project, sequencing

“Human Connectome Project marks its first phase,” National Institutes of Health, June 8, 2016. https://www.nih.gov/news-events/news-releases/human-connectome-project-marks-its-first-phase

small portions of anonymous donors’ genomes. Eventually, the project was completed in 2003, with a reference genome established based on those anonymous donors. This served as a springboard for future work in genomics. Through the Human Genome Project (HGP), scientists now have the ability to identify genetic

variants consistent with certain diseases for only $1,000 instead of billions. As research continues and questions of the origins of disease become more complex, an interesting question arises: what if, along with mapping the human genome, we are also able to map the connections in the human brain?

Scientists like Dr. Bobby Kasthuri at the University of Chicago focus their work around that very question, working in a field known as connectomics. Connectomics, previously known as hodology, is the study of connectomes, which are comprehensive maps of the connections in an organism’s nervous system. With roughly 100 billion neurons in the human brain and an estimated 1 quadrillion connections between them, this is certainly no easy feat. Nevertheless, there are techniques currently in use. Macroscopically, diffusion MRIs can be used to show fiber crossings in regions like the optic chiasm or the caudate nucleus, which neighbors the internal capsule, a white matter tract with many myelinated axons that are important for signaling. Another more widely used technique, and particularly important to Dr. Kasthuri’s research, is electron microscopy. By slicing extremely thin segments of the brain and using fluorescent or molecular markers to identify different neurons, a map of connections in a specific brain region or the retina can be mapped. A world where an individual’s neuronal connections could be mapped for $1,000 may still be rather far into the future, but the field of connectomics surely leads an interesting inquiry into how our brains are connected and function.

Despite the rapid expansion of initiatives like connectomics and the Human Genome Project, they are rarely without controversy. For the HGP, many critics center their arguments around privacy and the possible perpetuation of stereotypes based on ethnicity, which helped pave the way for HIPAA to be created in 1996. These same questions are also prevalent in connectomics. On the issue of privacy, there are implications about the brain and the mind. If an individual’s connectome could be coded into a computer, is that computer sentient in the same way the individual is? Would the individual and the computer have the same consciousness? Additionally, the possibility of mapping brains of individuals of different races, religions, genders, sexual orientations, etc. could unintentionally aid discourse promoting physiological distinctions between demographics. These questions remain concerns of the distant future, but the implications of this research and possible regulations they may bring about should be discussed as an intrinsic part of connectomics as a field.

Regardless of the ethical quandaries, there are undeniably practical uses to connectomics that would greatly benefit healthcare as a whole, similar to the HGP. Through comparing connectomes of healthy patients to connectomes of patients with various conditions and neuropathies, scientists could gain insight into synaptic origins of neuropathic pain and possible treatments. While this would require a great deal of standardization related to how connectomes are developed, the principle of comparing connectomes seems to be a rather fundamental aspect of any clinical applications. Additionally, as precision medicine becomes increasingly more popular, the ability to affordably map a person’s neuronal connections could greatly individualize patient care, just as we have seen with the HGP in providing therapies to treat some cancers and rare childhood disorders. The exact future of clinical use of connectomics is unwritten, but some potential benefits lie clearly within view. Though the Human Genome Project required billions of dollars and a large team of scientists, along with facing a fair amount of criticism, the applications at both the lab bench and the patient bedside are progressively manifesting themselves as research fields advance. Connectomics may be new and comparatively more unheard of, but it seems likely that continued investment in the field can only benefit the biomedical field as a whole. There may be a difficult road to navigate ahead, with questions of regulations, standardization, and ethical implications, but connectomics has potential to promote further insights into the workings of the human brain and most importantly, to help many people living with neurological conditions.

James R. Anderson, "Exploring the retinal

connectome," Molecular Vision 17 (2011): 355-379. https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3036568/ "About the Human Genome Project," Human Genome Project Information, July 18, 2011. https://web.archive.org/web/20110902062606/ http://www.ornl.gov/sci/techresources/ Human_Genome/project/about.shtml V.J. Weeden, "Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers," NeuroImage 41, 4 (2008): 1267-1277. https://www. sciencedirect.com/science/article/pii/ S105381190800253X?via%3Dihub