Brain Science: Optogenetics and Expansion Microscopy

Here are two cutting-edge neuroscience technologies that may enable us to treat conditions like blindness, epilepsy and Alzheimer's.

Ed Boyden: Over the last decade what we’ve been doing is trying to build tools that let us watch and control the operation of the brain.  If we can understand the brain the way that we understand computers, for example, maybe we could understand the brain at such a level of detail that you could really comprehend how it generates things like thoughts and feelings, actions and sensations.  For example, one technology that we’ve developed is called optogenetics.

In optogenetics we install a gene that encodes for a light sensitive protein in a cell or a set of cells in the brain.  And then we can aim light at those cells down an optical fiber or with a scanning laser.  So then you can play back activity to the brain.  People have put artificial sensations into the brain.  Can you figure out how a smell is represented for example.  People can trigger emotions and some groups have done some pretty philosophically interesting experiments.  So, for example, a group at Cal Tech has activated certain clusters of cells deep, deep in the brains of mice.  And if it’s the right cluster you can actually trigger a mouse to become aggressive or violent. They’ll attack whatever’s next to them even if it’s like a rubber glove, right.

You can also study diseases.  You can, for example, turn off overactive cells in a seizure and you can actually shut down seizures in animal models with epilepsy. These technologies are mostly being used in animals to reveal how brain circuits might be changed for therapeutic benefit.  So, for example, my group collaborated with another group to figure out that certain brain patterns actually might help clean up the debris in Alzheimer’s disease.  From that knowledge you can then go and develop other noninvasive strategies to try to help prevent, reduce the effects of or reverse brain disorders.  However, some people are exploring whether optogenetics might someday be used in humans directly.  And one area that’s of great interest is blindness.  Millions of people cannot see because the photoreceptors in their eyes, the light capturing cells have died off.  If you could convert the rest of the eye into a camera though by installing the optogenetic tools in spared cells of the eye maybe you could help these people see again.

Another technology we’ve developed allows us to map the structure of the brain.  The brain is really dense and complicated.  In a cubic millimeter of your brain you have around 100,000 cells called neurons and they’re wired up.  They’re connected at junctions called synapses.  And there are about a billion synapses in that cubic millimeter.  So mapping how the brain is wired up is a truly daunting task.  How can you image such a complex 3D structure with the nanoscale precision required to map the wiring?  Well we do it through a fairly unconventional way.  In contrast to the last 300 years of imaging where you use a lens to magnify light coming from a sample we actually take pieces of brain and fuse them with a chemical that’s a lot like the stuff in baby diapers.  And then we add water.  The baby diaper material swells and blows up the brain to make it 100 times or 1,000 times or even more bigger by volume. 

So because we move all the molecules away from each other in a smooth even fashion we can map their relative organization.  My hope is if we can map out the key geometry of the brain and how molecules are organized maybe we could simulate a brain circuit while it’s doing something like constructing a decision or sensing something or performing an action.

It’s not a very good metaphor but imagine that the brain, you’re trying to solve the brain in the same way that you might solve a computer.  You need to control the computer.  That’s the keyboard.  We use optogenetics.  You need a map of the computer, the wiring.  That’s what we’re using expansion microscopy for.  And you need to watch the computer in action, the monitor.  And we’re still working on those technologies.  I hope we’ll have that solved in the next couple of years.  But if you can put those three things together – the wiring, the watching and the control you can do a lot of interrogation of how computational circuits work. 

 

Edward Boyden is a Hertz Foundation Fellow and recipient of the prestigious Hertz Foundation Grant for graduate study in the applications of the physical, biological and engineering sciences. A professor of Biological Engineering and Brain and Cognitive Sciences at MIT, Edward Boyden explains how expansion microscopy is helping us to understand how the brain is wired, and how human therapies will benefit. He also tackles optogenetics — a technology that controls cells with light — which he hopes will restore the eyesight of the blind, dial back Alzheimer’s disease, and shut down epilepsy seizures. With the support of the Fannie and John Hertz Foundation, he pursued a PhD in neurosciences from Stanford University.


The Hertz Foundation mission is to provide unique financial and fellowship support to the nation's most remarkable PhD students in the hard sciences. Hertz Fellowships are among the most prestigious in the world, and the foundation has invested over $200 million in Hertz Fellows since 1963 (present value) and supported over 1,100 brilliant and creative young scientists, who have gone on to become Nobel laureates, high-ranking military personnel, astronauts, inventors, Silicon Valley leaders, and tenured university professors. For more information, visit hertzfoundation.org.

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Political division is nothing new. Throughout American history there have been numerous flare ups in which the political arena was more than just tense but incideniary. In a letter addressed to William Hamilton in 1800, Thomas Jefferson once lamented about how an emotional fervor had swept over the populace in regards to a certain political issue at the time. It disturbed him greatly to see how these political issues seemed to seep into every area of life and even affect people's interpersonal relationships. At one point in the letter he states:

"I never considered a difference of opinion in politics, in religion, in philosophy, as cause for withdrawing from a friend."

Today, we Americans find ourselves in a similar situation, with our political environment even more splintered due to a number of factors. The advent of mass digital media, siloed identity-driven political groups, and a societal lack of understanding of basic discursive fundamentals all contribute to the problem.

Civil discourse has fallen to an all time low.

The question that the American populace needs to ask itself now is: how do we fix it?


Discursive fundamentals need to be taught to preserve free expression

In a 2017 Free Speech and Tolerance Survey by Cato, it was found that 71% of Americans believe that political correctness had silenced important discussions necessary to our society. Many have pointed to draconian university policies regarding political correctness as a contributing factor to this phenomenon.

It's a great irony that, colleges, once true bastions of free-speech, counterculture and progressiveness, have now devolved into reactionary tribal politics.

Many years ago, one could count on the fact that universities would be the first places where you could espouse and debate any controversial idea without consequence. The decline of staple subjects that deal with the wisdom of the ancients, historical reference points, and civic discourse could be to blame for this exaggerated partisanship boiling on campuses.

Young people seeking an education are given a disservice when fed biased ideology, even if such ideology is presented with the best of intentions. Politics are but one small sliver for society and the human condition at large. Universities would do well to instead teach the principles of healthy discourse and engagement across the ideological spectrum.

The fundamentals of logic, debate and the rich artistic heritage of western civilization need to be the central focus of an education. They help to create a well-rounded citizen that can deal with controversial political issues.

It has been found that in the abstract, college students generally support and endorse the first amendment, but there's a catch when it comes to actually practicing it. This was explored in a Gallup survey titled: Free Expression on Campus: What college students think about First amendment issues.

In their findings the authors state:

"The vast majority say free speech is important to democracy and favor an open learning environment that promotes the airing of a wide variety of ideas. However, the actions of some students in recent years — from milder actions such as claiming to be threatened by messages written in chalk promoting Trump's candidacy to the most extreme acts of engaging in violence to stop attempted speeches — raise issues of just how committed college students are to
upholding First Amendment ideals.

Most college students do not condone more aggressive actions to squelch speech, like violence and shouting down speakers, although there are some who do. However, students do support many policies or actions that place limits on speech, including free speech zones, speech codes and campus prohibitions on hate speech, suggesting that their commitment to free speech has limits. As one example, barely a majority think handing out literature on controversial issues is "always acceptable."

With this in mind, the problems seen on college campuses are also being seen on a whole through other pockets of society and regular everyday civic discourse. Look no further than the dreaded and cliche prospect of political discussion at Thanksgiving dinner.

Talking politics at Thanksgiving dinner

As a result of this increased tribalization of views, it's becoming increasingly more difficult to engage in polite conversation with people possessing opposing viewpoints. The authors of a recent Hidden Tribes study broke down the political "tribes" in which many find themselves in:

  • Progressive Activists: younger, highly engaged, secular, cosmopolitan, angry.
  • Traditional Liberals: older, retired, open to compromise, rational, cautious.
  • Passive Liberals: unhappy, insecure, distrustful, disillusioned.
  • Politically Disengaged: young, low income, distrustful, detached, patriotic, conspiratorial
  • Moderates: engaged, civic-minded, middle-of-the-road, pessimistic, Protestant.
  • Traditional Conservatives: religious, middle class, patriotic, moralistic.
  • Devoted Conservatives: white, retired, highly engaged, uncompromising,
    Patriotic.

Understanding these different viewpoints and the hidden tribes we may belong to will be essential in having conversations with those we disagree with. This might just come to a head when it's Thanksgiving and you have a mix of many different personalities, ages, and viewpoints.

It's interesting to note the authors found that:

"Tribe membership shows strong reliability in predicting views across different political topics."

You'll find that depending on what group you identify with, that nearly 100 percent of the time you'll believe in the same way the rest of your group constituents do.

Here are some statistics on differing viewpoints according to political party:

  • 51% of staunch liberals say it's "morally acceptable" to punch Nazis.
  • 53% of Republicans favor stripping U.S. citizenship from people who burn the American flag.
  • 51% of Democrats support a law that requires Americans use transgender people's preferred gender pronouns.
  • 65% of Republicans say NFL players should be fired if they refuse to stand for the anthem.
  • 58% of Democrats say employers should punish employees for offensive Facebook posts.
  • 47% of Republicans favor bans on building new mosques.

Understanding the fact that tribal membership indicates what you believe, can help you return to the fundamentals for proper political engagement

Here are some guidelines for civic discourse that might come in handy:

  • Avoid logical fallacies. Essentially at the core, a logical fallacy is anything that detracts from the debate and seeks to attack the person rather than the idea and stray from the topic at hand.
  • Practice inclusion and listen to who you're speaking to.
  • Have the idea that there is nothing out of bounds for inquiry or conversation once you get down to an even stronger or new perspective of whatever you were discussing.
  • Keep in mind the maxim of : Do not listen with the intent to reply. But with the intent to understand.
  • We're not trying to proselytize nor shout others down with our rhetoric, but come to understand one another again.
  • If we're tied too closely to some in-group we no longer become an individual but a clone of someone else's ideology.

Civic discourse in the divisive age

Debate and civic discourse is inherently messy. Add into the mix an ignorance of history, rabid politicization and debased political discourse, you can see that it will be very difficult in mending this discursive staple of a functional civilization.

There is still hope that this great divide can be mended, because it has to be. The Hidden Tribes authors at one point state:

"In the era of social media and partisan news outlets, America's differences have become
dangerously tribal, fueled by a culture of outrage and taking offense. For the combatants,
the other side can no longer be tolerated, and no price is too high to defeat them.
These tensions are poisoning personal relationships, consuming our politics and
putting our democracy in peril.


Once a country has become tribalized, debates about contested issues from
immigration and trade to economic management, climate change and national security,
become shaped by larger tribal identities. Policy debate gives way to tribal conflicts.
Polarization and tribalism are self-reinforcing and will likely continue to accelerate.
The work of rebuilding our fragmented society needs to start now. It extends from
re-connecting people across the lines of division in local communities all the way to
building a renewed sense of national identity: a bigger story of us."

We need to start teaching people how to approach subjects from less of an emotional or baseless educational bias or identity, especially in the event that the subject matter could be construed to be controversial or uncomfortable.

This will be the beginning of a new era of understanding, inclusion and the defeat of regressive philosophies that threaten the core of our nation and civilization.