The new nature vs nurture: are you your genome or your connectome?

The nature vs nurture debate is over. Scientists and philosophers now know that an interplay between both shapes who we are at the level of the genome. Genes have the magnificent ability of both programing an organism and responding to all sorts of environmental cues.

Today, however, a new kid on the block named “connectomics” is ruffling feathers in many scientific circles. How do we begin to relate the brain’s immensely complicated structure to its function? What can this tell us about human nature that genetics has not? Watch as MIT neuroscientist Sebastian Seung ushers in the age of the Connectome, a complete map of the human brain, in order to advance our understanding of the human story.

In 1953, Watson and Crick unraveled the double helical structure of DNA. A mere 50 years later in 2003, the Human Genome Project kept its promise to unravel the 3 bilion units of information that comprise our hereditary makeup, our genes. Sequencing all these bits of DNA has revolutionized our understanding of the genetic basis of all sorts of diseases, such as Alzheimer’s and cancer, autism and diabetes.

And yet, despite their unquestionable importance — from vindicating Darwin’s theory of evolution to providing organisms with informational microvehicles — genes can’t possibly be everything. The numbers do not add up. The connections between brain cells, for instance, far exceed the number of genes in the human genome — so gene’s are a significant part of the human story, but this story is incomplete. Even though we live in an era in which every other science article provides wonderful evidence for “a significant genetic link between trait X and disease Y,” much of who we are remains elusive.

Let’s start with the one fact that neurosciensts love to recycle because of its power to humble: the brain consists of 100 billion neurons and each individual neuron can make up to 10 thousand connections with other neurons. The amount of possible connections between all the neurons in the brain (10 followed by 12 zeroes) far exceeds the number of stars in the galaxy by a mile. It’s no wonder that seemingly magical stuff happens, like consciousness or ideas of Gods, in this fantastically complex lump of protoplasm.

How do we go about tracing the entire brain? Growing up, most of us enjoyed finishing those “connect the dots” books. Page after page, we’d pencil in lines between seemingly disjointed dots until a picture of, say, a giraffe finally emerged. Neuroscientists still play this game but with slightly different and more expensive tools.

In the lab, neurons are the dots; dyes that color in neurons are the pencils; and, the picture that emerges shows the connections that any given neuron makes with another. Connectomics is a large-scale attempt to map out all the connections in the brain, an attempt to color in our neural circuits — the very stuff from which our thoughts and feelings and actions arise.

A fluffy slice of bread is a cross-section of the bigger and freshly-baked loaf from which it came. The carb-filled loaf itself, of course, would begin to take shape if we stacked each slice, one on top of the other. Sectioning the brain, slice after slice, uses the same idea. Seung and colleagues essentially slice the brain into tiny sections (on the order of microns) and combine dyes to stain neurons with computer programs to analyze the massive amounts of data in order to flesh out a true snapshot of neural circuitry.

As Seung puts it, “Before researchers study a single neuron under a microscope, they inject it with a stain. The neurons around it remain invisible because without the stain they are transparent. This technique is valuable for seeing the shape of a single neuron clearly. However, it does not give an accurate impression of what the brain is really like, because neurons are not islands in the brain. Instead, their forking branches are tightly entangled with each other. The brain can be compared to a giant bowl of spaghetti, in which each strand has been replaced by a complex, branched noodle. Because their branches are so tightly entangled, neurons are locked in a multi-way embrace.”

Connectomics promises to put all sorts of hypothesis-driven claims to the test: Can we accurately readout a specific memory — long believed to be at least partly a result of changes in neural connections — by knowing the brain’s structure? Is intelligence really a result of larger brain volume? What are the structural differences between healthy brains and brains with neurodegenerative disorders, otherwise known as connectopathies? Are differences in mental abilities a result of differences in neural wiring? Until recently, these lofty questions have remained the province of speculation with only some, often controversial, empirical support. Connectomics will raise the spatial resolution to unprecedented levels and hone in on some possible answers.

However, let’s not overhype the field too soon, either. One caveat has to do with how neural connections change over time. The strength, or “synaptic weight,” of the connection between two brain cells often changes during various types of learning, for instance. This is the process that the Canadian psychologist Donald Hebb correctly proposed in 1949 and is now known as “Hebb’s Rule.” It is summarized by the oft-quoted propostion, “Neurons that fire together wire together.” Admittedly, Seung’s model only partly addresses how synaptic weights change over time.

Any memory that his team hopes to read out must be defined strictly as an anatomical change in neural architecture — as changes in the projections to and from neurons. This dismisses the inevitable changes that go on at the molecular level but that are equally important for representing information in the brain. Such changes happen to levels of neurotransmitters, receptor densities, gene expression and protein synthesis. Neural anatomical tracings can only infer these changes.

Nonetheless, although in its infancy, connectomics could yield novel insight regarding how the brain achieves the mind at the level of neural networks. Whether or not a “connectomic revolution” awaits us is up for grabs. Regardless, Seung and his colleagues are at the forefront of neuroscience, slowly blurring the lines between neurons and circuits and behavior. Somewhere along the way and across these levels of analysis, “we” happen. Who knows? Maybe one day we will really achieve Issaac Asimov’s vision of uploading our brains onto computers. This, for now, is still the realm of science fiction, but for some like Seung, it is a hypothesis ripe for testing once the technology catches up.

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One response to “The new nature vs nurture: are you your genome or your connectome?

  1. Fascinating!

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