from the world's big
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.
Edward Boyden is a professor of Biological Engineering and Brain and Cognitive Sciences at the MIT Media Lab and the McGovern Institute for Brain Research at MIT. He leads the Media Lab’s Synthetic Neurobiology group, which develops tools for analyzing and repairing complex biological systems, such as the brain, and applies them systematically both to reveal ground truth principles of biological function and to repair these systems. These technologies, often created in interdisciplinary collaborations, include expansion microscopy (which enables complex biological systems to be imaged with nanoscale precision) optogenetic tools (which enable the activation and silencing of neural activity with light,) and optical, nanofabricated, and robotic interfaces (which enable recording and control of neural dynamics). Boyden has launched an award-winning series of classes at MIT, which teach principles of neuroengineering, starting with the basic principles of how to control and observe neural functions, and culminating with strategies for launching companies in the nascent neurotechnology space. He also co-directs the MIT Center for Neurobiological Engineering, which aims to develop new tools to accelerate neuroscience progress. Amongst other recognitions, Boyden has received the Breakthrough Prize in Life Sciences (2016), the BBVA Foundation Frontiers of Knowledge Award (2015), the Society for Neuroscience Young Investigator Award (2015), the Carnegie Prize in Mind and Brain Sciences (2015), the Jacob Heskel Gabbay Award (2013), the Grete Lundbeck Brain Prize (2013), the NIH Director's Pioneer Award (2013), the NIH Director's Transformative Research Award (twice, 2012 and 2013), and the Perl/UNC Neuroscience Prize (2011). He was also named to the World Economic Forum Young Scientist list (2013), MIT Technology Review’s international "Top 35 Innovators under Age 35" list (2006), and his work was included in Nature Methods "Method of the Year" in 2010. Boyden’s Media Lab group has hosted hundreds of visitors interested in learning how to use new biotechnologies. He also regularly teaches at summer courses and workshops in neuroscience, and delivers lectures to the broader public, including talks at TED (2011) and the World Economic Forum (2012, 2013, 2016). He received his PhD in neurosciences from Stanford University as a Hertz Fellow, where he discovered that the molecular mechanisms used to store a memory are determined by the content to be learned. Before his doctorate, he received three degrees in electrical engineering, computer science, and physics from MIT. Boyden has contributed to more than 300 peer-reviewed papers, current or pending patents, and articles, and has given over 300 invited talks on the work of the Media Lab’s Synthetic Neurobiology group.
Edward Boyden is a professor of Biological Engineering and Brain and Cognitive Sciences at the MIT Media Lab and the McGovern Institute for Brain Research at MIT. He leads the Media Lab’s Synthetic Neurobiology group, which develops tools for analyzing and repairing complex biological systems, such as the brain, and applies them systematically both to reveal ground truth principles of biological function and to repair these systems.
These technologies, often created in interdisciplinary collaborations, include expansion microscopy (which enables complex biological systems to be imaged with nanoscale precision) optogenetic tools (which enable the activation and silencing of neural activity with light,) and optical, nanofabricated, and robotic interfaces (which enable recording and control of neural dynamics).
Boyden has launched an award-winning series of classes at MIT, which teach principles of neuroengineering, starting with the basic principles of how to control and observe neural functions, and culminating with strategies for launching companies in the nascent neurotechnology space. He also co-directs the MIT Center for Neurobiological Engineering, which aims to develop new tools to accelerate neuroscience progress.
Amongst other recognitions, Boyden has received the Breakthrough Prize in Life Sciences (2016), the BBVA Foundation Frontiers of Knowledge Award (2015), the Society for Neuroscience Young Investigator Award (2015), the Carnegie Prize in Mind and Brain Sciences (2015), the Jacob Heskel Gabbay Award (2013), the Grete Lundbeck Brain Prize (2013), the NIH Director's Pioneer Award (2013), the NIH Director's Transformative Research Award (twice, 2012 and 2013), and the Perl/UNC Neuroscience Prize (2011). He was also named to the World Economic Forum Young Scientist list (2013), MIT Technology Review’s international "Top 35 Innovators under Age 35" list (2006), and his work was included in Nature Methods "Method of the Year" in 2010.
Boyden’s Media Lab group has hosted hundreds of visitors interested in learning how to use new biotechnologies. He also regularly teaches at summer courses and workshops in neuroscience, and delivers lectures to the broader public, including talks at TED (2011) and the World Economic Forum (2012, 2013, 2016).
He received his PhD in neurosciences from Stanford University as a Hertz Fellow, where he discovered that the molecular mechanisms used to store a memory are determined by the content to be learned. Before his doctorate, he received three degrees in electrical engineering, computer science, and physics from MIT. Boyden has contributed to more than 300 peer-reviewed papers, current or pending patents, and articles, and has given over 300 invited talks on the work of the Media Lab’s Synthetic Neurobiology group.
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.
Higher education faces challenges that are unlike any other industry. What path will ASU, and universities like ASU, take in a post-COVID world?
- Everywhere you turn, the idea that coronavirus has brought on a "new normal" is present and true. But for higher education, COVID-19 exposes a long list of pernicious old problems more than it presents new problems.
- It was widely known, yet ignored, that digital instruction must be embraced. When combined with traditional, in-person teaching, it can enhance student learning outcomes at scale.
- COVID-19 has forced institutions to understand that far too many higher education outcomes are determined by a student's family income, and in the context of COVID-19 this means that lower-income students, first-generation students and students of color will be disproportionately afflicted.
What conditions of the new normal were already appreciated widely?<p>First, we understand that higher education is unique among industries. Some industries are governed by markets. Others are run by governments. Most operate under the influence of both markets and governments. And then there's higher education. Higher education as an "industry" involves public, private, and for-profit universities operating at small, medium, large, and now massive scales. Some higher education industry actors are intense specialists; others are adept generalists. Some are fantastically wealthy; others are tragically poor. Some are embedded in large cities; others are carefully situated near farms and frontiers.</p> <p>These differences demonstrate just some of the complexities that shape higher education. Still, we understand that change in the industry is underway, and we must be active in directing it. Yet because of higher education's unique (and sometimes vexing) operational and structural conditions, many of the lessons from change management and the science of industrial transformation are only applicable in limited or highly modified ways. For evidence of this, one can look at various perspectives, including those that we have offered, on such topics as <a href="https://www.insidehighered.com/digital-learning/blogs/rethinking-higher-education/lessons-disruption" target="_blank">disruption</a>, <a href="https://www.nytimes.com/2020/02/20/education/learning/education-technology.html" target="_blank">technology management</a>, and so-called "<a href="https://www.insidehighered.com/sites/default/server_files/media/Excerpt_IHESpecialReport_Growing-Role-of-Mergers-in-Higher-Ed.pdf" target="_blank">mergers and acquisitions</a>" in higher education. In each of these spaces, the "market forces" and "market rules" for higher education are different than they are in business, or even in government. This has always been the case and it is made more obvious by COVID-19.</p> <p>Second, with so much excitement about innovation in higher education, we sometimes lose sight of the fact that students are—and should remain—the core cause for innovation. Higher education's capacity to absorb new ideas is strong. But the ideas that endure are those designed to benefit students, and therefore society. This is important to remember because not all innovations are designed with students in mind. The recent history of innovation in higher education includes several cautionary tales of what can happen when institutional interests—or worse, <a href="https://www.insidehighered.com/news/2016/02/09/apollos-new-owners-seek-fresh-start-beleaguered-company" target="_blank">shareholder</a> interests—are placed above student well-being.</p>
Photo: Getty Images<p>Third, it is abundantly apparent that universities must leverage technology to increase educational quality and access. The rapid shift to delivering an education that complies with social distancing guidelines speaks volumes about the adaptability of higher education institutions, but this transition has also posed unique difficulties for colleges and universities that had been slow to adopt digital education. The last decade has shown that online education, implemented effectively, can meet or even surpass the quality of in-person <a href="https://link-springer-com.ezproxy1.lib.asu.edu/article/10.1007/s10639-019-10027-z" target="_blank">instruction</a>.</p><p>Digital instruction, broadly defined, leverages online capabilities and integrates adaptive learning methodologies, predictive analytics, and innovations in instructional design to enable increased student engagement, personalized learning experiences, and improved learning outcomes. The ability of these technologies to transcend geographic barriers and to shrink the marginal cost of educating additional students makes them essential for delivering education at scale.</p><p>As a bonus, and it is no small thing given that they are the core cause for innovation, students embrace and enjoy digital instruction. It is their preference to learn in a format that leverages technology. This should not be a surprise; it is now how we live in all facets of life.</p><p>Still, we have only barely begun to conceive of the impact digital education will have. For example, emerging virtual and augmented reality technologies that facilitate interactive, hands-on learning will transform the way that learners acquire and apply new knowledge. Technology-enabled learning cannot replace the traditional college experience or ensure the survival of any specific college, but it can enhance student learning outcomes at scale. This has always been the case, and it is made more obvious by COVID-19.</p>
What conditions of the new normal were emerging suspicions?<p>Our collective thinking about the role of institutional or university-to-university collaboration and networking has benefitted from a new clarity in light of COVID-19. We now recognize more than ever that colleges and universities must work together to ensure that the American higher education system is resilient and sufficiently robust to meet the needs of students and their families.</p> <p>In recent weeks, various commentators have suggested that higher education will face a wave of institutional <a href="https://www.businessinsider.com/scott-galloway-predicts-colleges-will-close-due-to-pandemic-2020-5" target="_blank">closures</a> and consolidations and that large institutions with significant online instruction capacity will become dominant.</p> <p>While ASU is the largest public university in the United States by enrollment and among the most well-equipped in online education, we strongly oppose "let them fail" mindsets. The strength of American higher education relies on its institutional diversity, and on the ability of colleges and universities to meet the needs of their local communities and educate local students. The needs of learners are highly individualized, demanding a wide range of options to accommodate the aspirations and learning styles of every kind of student. Education will become less relevant and meaningful to students, and less responsive to local needs, if institutions of higher learning are allowed to fail. </p> <p>Preventing this outcome demands that colleges and universities work together to establish greater capacity for remote, distributed education. This will help institutions with fewer resources adapt to our new normal and continue to fulfill their mission of serving students, their families, and their communities. Many had suspected that collaboration and networking were preferable over letting vulnerable colleges fail. COVID-19's new normal seems to be confirming this.</p>
President Barack Obama delivers the commencement address during the Arizona State University graduation ceremony at Sun Devil Stadium May 13, 2009 in Tempe, Arizona. Over 65,000 people attended the graduation.
Photo by Joshua Lott/Getty Images<p>A second condition of the new normal that many had suspected to be true in recent years is the limited role that any one university or type of university can play as an exemplar to universities more broadly. For decades, the evolution of higher education has been shaped by the widespread imitation of a small number of elite universities. Most public research universities could benefit from replicating Berkeley or Michigan. Most small private colleges did well by replicating Williams or Swarthmore. And all universities paid close attention to Harvard, Princeton, MIT, Stanford, and Yale. It is not an exaggeration to say that the logic of replication has guided the evolution of higher education for centuries, both in the US and abroad.</p><p>Only recently have we been able to move beyond replication to new strategies of change, and COVID-19 has confirmed the legitimacy of doing so. For example, cases such as <a href="https://www.washingtonpost.com/education/2020/03/10/harvard-moves-classes-online-advises-students-stay-home-after-spring-break-response-covid-19/" target="_blank">Harvard's</a> eviction of students over the course of less than one week or <a href="https://www.nhregister.com/news/coronavirus/article/Mayor-New-Haven-asks-for-coronavirus-help-Yale-15162606.php" target="_blank">Yale's apparent reluctance</a> to work with the city of New Haven, highlight that even higher education's legacy gold standards have limits and weaknesses. We are hopeful that the new normal will include a more active and earnest recognition that we need many types of universities. We think the new normal invites us to rethink the very nature of "gold standards" for higher education.</p>
A graduate student protests MIT's rejection of some evacuation exemption requests.
Photo: Maddie Meyer/Getty Images<p>Finally, and perhaps most importantly, we had started to suspect and now understand that America's colleges and universities are among the many institutions of democracy and civil society that are, by their very design, incapable of being sufficiently responsive to the full spectrum of modern challenges and opportunities they face. Far too many higher education outcomes are determined by a student's family income, and in the context of COVID-19 this means that lower-income students, first-generation students and students of color will be disproportionately afflicted. And without new designs, we can expect postsecondary success for these same students to be as elusive in the new normal, as it was in the <a href="http://pellinstitute.org/indicators/reports_2019.shtml" target="_blank">old normal</a>. This is not just because some universities fail to sufficiently recognize and engage the promise of diversity, this is because few universities have been designed from the outset to effectively serve the unique needs of lower-income students, first-generation students and students of color.</p>
Where can the new normal take us?<p>As colleges and universities face the difficult realities of adapting to COVID-19, they also face an opportunity to rethink their operations and designs in order to respond to social needs with greater agility, adopt technology that enables education to be delivered at scale, and collaborate with each other in order to maintain the dynamism and resilience of the American higher education system.</p> <p>COVID-19 raises questions about the relevance, the quality, and the accessibility of higher education—and these are the same challenges higher education has been grappling with for years. </p> <p>ASU has been able to rapidly adapt to the present circumstances because we have spent nearly two decades not just anticipating but <em>driving</em> innovation in higher education. We have adopted a <a href="https://www.asu.edu/about/charter-mission-and-values" target="_blank">charter</a> that formalizes our definition of success in terms of "who we include and how they succeed" rather than "<a href="https://www.washingtonpost.com/opinions/2019/10/17/forget-varsity-blues-madness-lets-talk-about-students-who-cant-afford-college/" target="_blank">who we exclude</a>." We adopted an entrepreneurial <a href="https://president.asu.edu/read/higher-logic" target="_blank">operating model</a> that moves at the speed of technological and social change. We have launched initiatives such as <a href="https://www.instride.com/how-it-works/" target="_blank">InStride</a>, a platform for delivering continuing education to learners already in the workforce. We developed our own robust technological capabilities in ASU <a href="https://edplus.asu.edu/" target="_blank">EdPlus</a>, a hub for research and development in digital learning that, even before the current crisis, allowed us to serve more than 45,000 fully online students. We have also created partnerships with other forward-thinking institutions in order to mutually strengthen our capabilities for educational accessibility and quality; this includes our role in co-founding the <a href="https://theuia.org/" target="_blank">University Innovation Alliance</a>, a consortium of 11 public research universities that share data and resources to serve students at scale. </p> <p>For ASU, and universities like ASU, the "new normal" of a post-COVID world looks surprisingly like the world we already knew was necessary. Our record breaking summer 2020 <a href="https://asunow.asu.edu/20200519-sun-devil-life-summer-enrollment-sets-asu-record" target="_blank">enrollment</a> speaks to this. What COVID demonstrates is that we were already headed in the right direction and necessitates that we continue forward with new intensity and, we hope, with more partners. In fact, rather than "new normal" we might just say, it's "go time." </p>
Hollywood has created an idea of aliens that doesn't match the science.
- Ask someone what they think aliens look like and you'll probably get a description heavily informed by films and pop culture. The existence of life beyond our planet has yet to be confirmed, but there are clues as to the biology of extraterrestrials in science.
- "Don't give them claws," says biologist E.O. Wilson. "Claws are for carnivores and you've got to be an omnivore to be an E.T. There just isn't enough energy available in the next trophic level down to maintain big populations and stable populations that can evolve civilization."
- In this compilation, Wilson, theoretical physicist Michio Kaku, Bill Nye, and evolutionary biologist Jonathan B. Losos explain why aliens don't look like us and why Hollywood depictions are mostly inaccurate.
Sallie Krawcheck and Bob Kulhan will be talking money, jobs, and how the pandemic will disproportionally affect women's finances.
Manly Bands wanted to improve on mens' wedding bands. Mission accomplished.
- Manly Bands was founded in 2016 to provide better options and customer service in men's wedding bands.
- Unique materials include antler, dinosaur bones, meteorite, tungsten, and whiskey barrels.
- The company donates a portion of profits to charity every month.
Scientists uncovered the secrets of what drove some of the world's last remaining woolly mammoths to extinction.
Every summer, children on the Alaskan island of St Paul cool down in Lake Hill, a crater lake in an extinct volcano – unaware of the mysteries that lie beneath.