Q & A with Mitchell H. Katz

TEDMED: In your TEDMED 2018 talk, you shared that you believe that healthcare in the United States is built on a middle-class model that often does not meet the needs of low-income patients. In your opinion, what are some of the assumptions made in the current model?

Mitchell H. Katz: Health care in this country assumes you can take time off from work to see the doctor, that you speak English, that you are literate, that you have a working phone, a safe home and healthy food to eat. 

The current model is simply not designed to be responsive for people like one of my patients who developed partial blindness in both eyes but didn’t come to see me until days later because he had to work in order to pay the rent. Or my hospitalized patient from West Africa who spoke a dialect so unusual that we could only find one translator who could understand him.  That translator only worked one afternoon a week. My patient needed to communicate every day. Or the diabetic patient who is homeless and has no refrigerator to keep his insulin or steady supply of food to keep his blood sugar under control. 

That’s one of the reasons why it’s been so difficult for us to close the disparity in health care that exists along economic lines despite the expansion of health insurance under the ACA or Obamacare.  

TM: Being aware of these assumptions, what are some of the actionable ways that providers can better meet the needs of their low-income patients?

MK: We need to redesign the system to meet patients where they are and remove obstacles. We need to provide what they need, not what we think they need. The right prescription for a homeless patient is housing. For non-English speaking patients, translation is as important as a prescription pad. And for people who do not have a steady supply of food, there is a variety of solutions. In New York City, we hired a bunch of enrollers to get our patients into the supplemental nutrition program known as Food Stamps. Other health systems are including food pantries at primary care clinics, or distributing maps of community food banks and soup kitchens.  

But more than anything else, I think low-income patients benefit from having a primary care doctor.  They need a team of people who can help them access the medical and nonmedical services they need.  So many are disenfranchised from other community supports, and they really benefit from the care and continuity provided by primary care.  

TM: Having run the safety net systems in San Francisco, Los Angeles and now New York City, you have an in-depth knowledge of the health needs in each area. Are there any striking similarities or differences between the needs in each city?

MK: One of the most obvious differences I’ve noticed is that in New York City, people don’t use primary care – they rely on specialists for every part of the body. I like to joke that folks here have left earlobe specialists and right ankle surgeons. That means there is less focus on prevention and wellness. That’s why I’m particularly excited about NYC Care, our new health access program for people who are not eligible for insurance. We can guarantee NYC Care members a dedicated primary care provider and a first visit in two weeks or less to help keep them healthy. 

TM: In your experience in creating housing as a public health response, what resources need to come together to provide the necessary support, financially and otherwise, to achieve this? 

MK: In Los Angeles, we housed 4,700 chronically homeless persons suffering from medical illness, mental illness, addiction.  It really takes a village to make this possible. We need non-profit developers whose mission is to serve. We need health care providers and community based organizations that can provide onsite services, state and local governments that prioritize housing as a public health issue, supportive neighbors who welcome instead of fear and protest the influx of formerly homeless or substance users to their communities. And we need banks willing to finance these non-traditional construction projects.   

TM: What is your hope for the future of the U.S. health care system?

MK: My hope is that people recognize the vital role of primary care in delivering high quality health care to diverse populations.  That means valuing primary care doctors, both financially and spiritually, so that medical students want to become primary care doctors and truly meet the needs of their patients. 

Massive Science on Yaniv Erlich

Massive Science is a digital science media publication that brings together scientists and the science-curious public. The team at Massive joined us at TEDMED 2018 and covered talks by various speakers including Yaniv Erlich. Check out their coverage of Yaniv’s TEDMED 2018 talk below.


Humans have an inherent social drive, and in this age of social media, we are more connected than ever. However, by constructing the world’s largest family tree comprising 125 million people, computational geneticist Yaniv Erlich, has shown that some of these connections run deeper — down into our genes. Erlich, who is a professor and researcher at Columbia University and CSO of MyHeritage.com, is revolutionizing the field of genomics by linking genealogical data provided online by volunteers to DNA with striking accuracy. Earlier this year, Erlich and his colleagues sent a shock wave through the field of genetics by showing that it is possible to uncover the identities of males who have taken part in “anonymous” genetic research without ever matching their data to a sample of their DNA. All you really need is the internet.

“Smoking…determines ten years of our life expectancy, which is twice as much as what our genetics determines.”

Genomic data is incredibly powerful. It can reveal migration patterns, or uncover interesting details like the distance people move from their place of birth to procreate. But more importantly, genomic data allows us to ask questions about human health, like how much genetic variations account for differences in individual life-spans. Large family trees allow us to analyze both close relatives and distant relatives, teasing apart the difference between genetic variations and environmental factors. Erlich, for example, found that genes account for only 15 percent of the differences in individual life-spans, on average about five years. Speaking about these surprising findings, Erlich says, “I think there is this notion that there is some fountain of youth in our genome, and we just have to find the gene to unlock it. But it doesn’t seem this is the case.” Erlich explains that since 1960, lifespans have increased linearly by about two months every year, despite two World Wars. Despite the many catastrophes of the 20th century, lifespans continued to steadily grow. Erlich says these findings mean that our actions might matter more than our genes. “Smoking for example, determines ten years of our life expectancy, which is twice as much as what our genetics determines.”

While genes seem to have relatively little impact on our life span, genomic data has allowed us to identify risk factors for a numbers of diseases. Using genome-wide association studies (GWAS), it’s possible to link genetic variants in different individuals to particular traits. The more statistically significant the link is, the more the data looks like the skyline of Manhattan. Ten years ago, Erlich says, these Manhattan plots actually looked more like the skyline of Los Angeles. But bigger sample sizes have become easier for researchers to access, thanks to initiatives like the UK Biobank, where an increasing number of genetic risk factors are being identified. Using data from more than 100,000 donors, obtained through the website DNA.land, Erlich has himself been able to discover the genetic bases for several traits in Israeli families.

With the help of civilian genealogy enthusiasts, genomic data is changing not only the landscape of health care, but forensics too. In April, thanks to the website GEDmatch, the FBI was able to link DNA from the unidentified Golden State Killer to a third cousin of the suspect who had voluntarily provided their own DNA to the free online genealogy database. By building a large family tree, and scanning the different branches of the tree until they found a profile that exactly matched what they knew about the serial killer, they were able to track down the suspect, test his DNA, and charge him.

A Manhattan plot. The bars that rise higher than the rest are the ones of interest.
Ikram et al 2010 PLoS Genetics

Erlich is impressed by the power of genomics to improve demography, healthcare, and forensics. But he agrees there are many issues that still need to be addressed. For example, since these databases primarily contain people of European descent, non-European populations with certain genetic risk factors are missed, while risk factors identified in these European populations may not have the same implications for other groups. The most obvious reason for this disparity is economics. But many genealogy websites are free, and the price of DNA tests has dropped to as little as $49. Another reason may be access to family records. As Erlich says, “My family died in the Holocaust, so I have no means to go beyond a certain number of generations. It’s all lost.” A lack of record-keeping is also a problem for many populations. There’s also the question of social influence. “If I know someone who is doing genealogy, I’m now more willing to also do it. When you start with one community, it spreads from that community unequally.” Erlich does not have the answers for how to remedy the issue of diversity in databases, but believes that governments, at least in countries equipped with the resources, should take greater responsibility for driving genomic medicine.

Which of these people are represented in biobanks?
Serge Melki via Wikimedia Commons

Another complex issue is the issue of privacy. When it comes to genetic information, many of us are concerned that employers and insurance companies may use this information unethically. According to the Genetic Information Nondiscrimination Act of 2008 (GINA), employers and insurance companies cannot use our genetic information without our consent. But there are some major loopholes; for example, GINA doesn’t apply to life insurance. There’s also the question of how law enforcement should be allowed to use genetic information. The Golden State Killer case in particular raises many questions about privacy. Interestingly, 60 percent of Americans of European heritage (because they are over-represented in databases) have relinquished genetic information that could be used by law enforcement, and within three years, this number is expected to rise to 99 percent. Erlich says he’s not scared of these techniques being abused. He’s more worried about national security. “I’m more concerned about foreign governments using the same techniques to identify U.S. individuals. Think about CIA operation in some countries. The whole point is that it’s covert—you don’t know the identities of these people. It’s very easy to disguise your face and get a fake passport, but you can’t change your DNA.” At the end of the day, there are no easy answers. “It’s a tricky question of justice, and how to define that,” he says, pointing toward the need to make genetic information part of a public good, rather than be used for monetary gain. But the limits may be hard to find. He says, “I don’t know what’s the right answer.”


About the author: Yewande Pearse was born and bred in North London. She is now a Research Fellow based at LA Biomed, in affiliation with the University of California, Los Angeles (UCLA). She completed her PhD in Neuroscience at the Institute of Psychiatry in 2016, which focused on the potential use of gene therapy for the treatment of Batten disease, a fatal neurological pediatric disease. She is now working on stem cell gene therapy using CRISPR-Cas9 to treat Sanfilippo Syndrome. Before completing her PhD, she worked in the areas of Stroke and Huntington’s disease research and also worked in a care capacity, with people living with Autism, suicidal ideation, dementia and HIV Associated Neurocognitive Disorder.

Q & A with Yaniv Erlich

TEDMED: In your TEDMED 2018 talk, you describe “Uncle Bernie,” the family genealogist who corners family members to get more information. Are you the genealogist in your family? When did your interest in genealogy begin?

Yaniv Erlich: [laughing] I liked genealogy quite a lot, especially as a child. Like many Israeli teenagers, I conducted my own genealogy project while I was in seventh grade. It was so enjoyable that I asked my mother to take me to the Museum of the Jewish People at Beit Hatfutsot; it had one of the only sources for genealogical information available at the time. I loved how history intersects with family stories, and the process of finding ancestors felt like detective work. I did such a good job on this project that it won the title of best genealogy project of the year at my middle school. Now, since genealogy is my work, it is no longer a hobby of mine and the family genealogist is my aunt. 

The last time I spent time on the genealogy of my family was after my father passed away 2 years ago. In some way, I felt that tracing my ancestors connected me to my father and his childhood–and reviewing the lifecycles of my family relatives gave me some serenity and comfort that the sorrow that I was experiencing was simply part of the endless rivers of generations.

Photo Credit: Yaniv Erlich

TM:  What was the catalyst for you to begin professional research on genetics and family trees?

YE: I was invited to join a commercial genealogy and social networking website by my third cousin, who was able to trace me and send an invitation email. At that time, I was about to finish my PhD studies and become more interested in human genetics. When I started documenting my family tree on the website, I was shocked to discover that many of my relatives already existed there! This got me thinking — family trees are one of the most valuable assets in human genetics. Yet, large family trees are very hard to collect. 

A few months later, I started my own independent research group at the Whitehead Institute of MIT. I decided to try to collect all the data from that website as one of the first projects of the lab, so I sent a cold email to the CTO of the website at that time, Amos Elliston. He immediately agreed and instructed me on how to collect the data. Eventually we downloaded 86 million public profiles from the website.

But over time it became a very long project. We actually spent 8 years from inception to publication. 

TM: Did you have any hurdles during the project?

YE: First, we had to substantially enhance and validate the dataset. The central question was whether we can trust datasets that were produced by amateur genealogists the same way that we trust family trees built by scientists. So we subjected the data to a massive number of tests, such as measuring the error rates of family trees, whether the individuals in these datasets represented the general population at the time, and the accuracy of the demographic details inserted by the genealogists. Second, we had to find the correct questions. In some ways, this dataset was a blessing and a curse because so many things can be evaluated using such datasets, and we had to think carefully about the focus of our study. Finally, we had to develop the computational infrastructure to answer those questions. Most genetic algorithms were developed to work with family trees with up to several thousand individuals. We had to develop and improve these algorithms to work on a scale of tens of millions of people.

TM: A lot of your research focuses on the role of genetics in longevity. What was the main thing you wanted to understand about longevity when you began your research? 

YE: Longevity is probably the most important trait because the question: “When am I going to die?” is imminent to us as individuals and as a society. Surprisingly, not a lot is known about the genetics of longevity. Some studies in the past suggested that 25% of the variance in longevity is attributed to genetic differences. However, these differences were never spotted by any study! 

In addition, there is a long-lasting debate in human genetics regarding the manner in which genetic variations affect traits. One camp argues that each genetic variant contributes independently to a trait regardless of the status of other variants. Another camp claims that the contribution of each variant is a complex function that is affected by the status of other variants. It is possible to find which camp is right by inspecting the correlation of the trait in various types of relatives, from, say, fourth cousins to full siblings. However, until our study, nobody was able to collect large family trees with enough relatives to robustly differentiate between the two camps.

Using our data, we inspected the longevity readout of millions of pairs of relatives. Our analysis shows that longevity is much less heritable than we thought before and only ~15% of the variance in the population can be attributed to genetic differences. Moreover, we showed that at least in the case of longevity, the first camp is the correct one. The value of each genetic variant is independent of the other variants. This is actually great news for precision medicine, because if each variant works independently, it means that it should be easier to find those longevity variants in the future.

TM: In your TEDMED talk, you spoke about the immense potential of biomedical research and the many insights we can gain from genealogy research. What’s the future of genealogy research?

YE: DNA! We currently see an ongoing revolution in the field. DNA tests enable genealogists to find relatives beyond the information permitted in genealogical records and as a tool to validate these records. In addition, DNA helps to solve cases when records are missing such in the case of adoptees, holocaust survivors, and even child trafficking. Thanks to the genomics revolution DNA tests are now highly affordable, democratizing access by growing segments of the population. A recent Technology Review article estimated that more than 26 million people took such tests and the uptake shows an exponential increase. Some estimate that in a decade most people in Western societies will have access to their DNA information, which means that we may be able to create the world’s family tree based also on DNA matches and not just genealogical information and family stories.

Q & A with Carl June

TEDMED: In your TEDMED 2018 Talkyou mentioned that cancer researchers had essentially given up on using the immune system to fight cancer, with the exception of cancers like cervical cancer and liver cancer.  What motivated you to look at the immune system differently, and even build your own synthetic immune system, to fight cancer cells? Did you receive skepticism from the medical community before your research was proven fruitful? 

Carl June: I have mentioned that I did my initial research while a medical research officer in the United States Navy. I was basically “conscripted” to do research in HIV even though my medical training was as an oncologist with specialization in leukemia. I was simply not permitted to do research in cancer. This turned out to be very fortunate turn of events because I learned how to use the HIV virus to engineer the immune system for people with HIV/AIDS. This gave me a completely different perspective when I moved to the University of Pennsylvania and began working on leukemia and lymphoma. 

And yes, there was skepticism. You better believe it! And it was well-deserved because for more than a hundred years people had tried to use the immune system to fight cancer with very disappointing results. In fact 10 years ago, there were less than five scientists working actively to make CAR T cells for cancer,  and now there are hundreds of laboratories around the world working on this problem. It is rare in science and medicine to see a shift of that magnitude in that time scale.

TM: CAR T cell infusions are the “first living drug in medicine,” as they stay alive and on patrol in the body for decades. Have other drugs followed this path?

CJ: As it happens, last week I got an email from the very first patient that we treated with CAR T cells for leukemia. The occasion of his email was that it was the nine-year anniversary since he had had his CAR T cell infusion and he wrote me to say how grateful he is for the remission. At this time I think we are safe to conclude that he is in fact cured. So that’s a very rewarding email to get! Scientifically we know from lab tests that his CAR T cells are still on patrol and in fact they are the first “living drugs”. I am confident that with the technologies we have today, including genome-editing, that there will be many more examples of living drugs created over the coming years. 

TM: At TEDMED, we like to think about each talk as sharing a “gift” with the community— a single idea that the audience takes away with them, that can change the way they think about a key issue or an “idea worth spreading”. What is the gift you’d like people to receive when watching your TEDMED Talk?

CJ: I have mentioned that I had many unplanned detours in my career. The gift I would like to leave with the community is that these twists and turns can be huge opportunities, and in my case, they led to the discovery of a cure for leukemia.  Sometimes creativity can emerge when you are forced to change your mindset.

Call for TEDMED 2020 Artist

At the heart of TEDMED’s mission is the quest for a deeper understanding of ourselves and the world around us. As tools for discovery, we recognize the essential roles that both science and art play in this pursuit. And yet, while science is rarely underappreciated in this search, art can often be overlooked. We believe that art serves an important role as a catalyst for innovation and creativity and provides the inspiration needed to birth new questions and new paths for scientific research. Art and science are inevitably intertwined, serving as inspiration for one another and constantly propelling us toward progress.

The roles that both science and art play in our health has been beautifully illustrated time and time again from our stage. At TEDMED 2018, Sound Alchemist, Yoko K. Sen, shared how dissonant sounds from hospital environments can become overwhelming to patients and can even run antithetical to the healing process. Yoko has dedicated her musical talents toward a better understanding of how sound impacts our emotions and she works to transform the auditory environment of hospitals with soothing melodies and tones. She’s the founder of Sen Sound, a social enterprise that aims to change the soundscape of medical spaces.

Similarly, award-winning architect Amanda Sturgeon discussed how we can rethink the design of spaces so that they emulate the surrounding environment, which has a positive impact on the occupants. Amanda and her team found that “biophilic buildings” – structures that embrace and borrow features found in the natural world – create spaces in which people are happier, healthier and more productive.

In 2018, the direct link between science and art was perhaps most strongly depicted in Marlène Oliver’s talk and art installation. Using imaging from MRIs and CT scans, she creates art that allows us to see how our digital selves exist in an abstract world of data. Every year, artists from across the artistic spectrum, contribute their talent and perspective to our program,  such as pianist Richard Kogan, painter Ted Meyer, art curator Christine McNabb, documentarian Holly Morris, improv performers Karen Stobbe and Mondy Carter, chef John La Puma, photographer Kitra Cahana, musician Gerardo Contino, and many more.  The talks themselves are also works of art. Each speaker carefully crafts their talk to share a unique gift with the TEDMED community. Even our speakers themselves become art, because an important part of our event design each year is to work with artists who create portraits of our speakers.

To come full circle, our 2018 portrait artist Marlene Morales Tollet is a perfect example of the art and science intersecting. Marlene is both a practicing ophthalmologist, specializing in comprehensive ophthalmology and oculoplastic surgery and an artist. We’ve been lucky to work with amazing artistic talent throughout the years, from widely acclaimed figures like Hanoch Piven and Victor Juhasz, to a collaborative project created by several RISD art students, to the fantastic work of Gabriel Gutierrez and Lauren Hess who were chosen from our community. These artists are invited to TEDMED and become an important part of our Delegation. Find out more about their beautiful work here.

LOOKING FOR THIS YEAR’S ARTIST
Again this year, we’re excited to begin a search for the artist or artists who will help us bring this year’s speaker portraits to life. As part of our search, we’re officially accepting artist nominations and applications for TEDMED 2020.

Just as every year, our chosen artist or artists will join our community for 3 days in Boston, MA at The Westin Boston Waterfront Hotel, March 2-4 for TEDMED 2020 (travel and accommodations covered by TEDMED).  If you are interested, or know someone who might be, read on!

ELIGIBILITY AND TIME FRAME
This call is open to amateur and professional artists, and all art mediums will be considered. While not required, the artist would ideally have a close tie to health and medicine. This could take form in the following ways:

  • Experience in the medical community
  • Experience working with patients
  • A personal story connecting the artist to health and medicine

ABOUT THE PROJECT
The artist will need to produce roughly 50 portraits over the course of the next few months. Illustrations will be based on reference photos that will be provided. Final portraits will need to be delivered as high res digital files based on our specifications.

The work will take place between November 2019 – January 2020.

HOW TO APPLY
To apply (or nominate an artist), please send an email to art@tedmed.com. Be sure to include a work sample, a brief bio, any relevant links and details about the best way to get in touch (email, cell, etc.). If the artist is a good fit, someone from our team will reach out.

Application deadline: Midnight, October 4, 2019.

Q&A with Emily F. Rothman

TEDMED: In your TEDMED 2018 talk, you briefly touched upon sex education in schools. Diving further – what does sex-ed look like in schools today and what would it look like in your ideal world? Would there be a standardized curriculum, what topics are critical to cover, and who is best positioned to share this information?

Emily F. Rothman: In the United States, sex-ed varies a lot state to state. In some places, adolescents are taught very basic information about sexual anatomy and reproduction, and perhaps about sexually transmitted infections, but nothing more. They are not taught, for example, that it is important to communicate with a partner about whether they are both enjoying sex. The American College of Obstetricians and Gynecologists (ACOG) Committee on Adolescent Health Care authored an opinion about what comprehensive sex education should include, which can be found here: https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-Adolescent-Health-Care/Comprehensive-Sexuality-Education?IsMobileSet=false .

In case that’s too long to read, I can summarize and say that teaching teens about the context in which we make our choices about sex–why we decide to have it, with whom, when, under what pressures, for what reasons, and how other people treat us because of sexual decisions, is important. Teenagers deserve to be invited to think about those kinds of deeper issues in order to become the people that they want to be. In terms of who is best positioned to provide that information, I think in an ideal world there would be consistent messaging from parents, teachers, media stars, and everyone in between that consent and pleasure are important and that sex is supposed to be fun and make all parties involved happy. If someone is not happy, you aren’t doing it right.

TM: You mentioned that the pornography industry is profiting off content that can, in many cases, depict women in a degrading manner. In your opinion, would placing restrictions on the pornography industry be worthwhile in the public health effort to reduce sexual violence – in the same vein in which restrictions have placed on tobacco companies to reduce smoking? 

EFR: Smoking causes 90% of lung cancer cases.  I don’t think that pornography causes 90% of sexual violence cases.  So if the question on the table is ‘how do we prevent sexual violence?’, I would not say that regulating the pornography industry is the quickest and most efficient way to do that in the same way that regulating tobacco companies is for lung cancer.  

But let’s say that the question on the table is ‘how do we prevent underage youth from seeing pornography, since there is a possibility it is bad for them?’ Some of the restrictions are already there, technically. In the U.S., pornography is not supposed to be shown to people who are younger than 18 years old, but nevertheless it’s too easy for young people to see explicit content. Making it more difficult for people less than 18 years old to see pornography would be good.  But–just like underage youth get ahold of cigarettes, alcohol, or anything else that is supposed to be off limits until they reach a certain age–there are going to be those who see pornography anyway, even with more barriers in place. That’s why a public health effort will be one that operates at multiple levels simultaneously. I agree that there should be some people thinking about the most effective and logical legislation and regulation, but also have other people thinking about shifting social norms and changing culture so that it values sexual consent above all else, and safety for everyone no matter their sexuality. While all of that is happening, we also need people thinking about the individuals who are most at risk for perpetrating sexual violence, and what prevents perpetration, to make sure we are doing everything that we can to discourage that behavior, including addressing their pornography access and use. It’s a bit like limiting the access of a person who has engaged in drunk driving to a car. We don’t limit the car industry from selling to people who use alcohol or tell everyone in society that they can’t have a car–but we do limit the people at high risk. In other words, an effective public health effort is measured and considers the problem from multiple angles. 

TM: Through pornography literacy, you were able to open a conversation about identity representation in pornography as a genre of media. What can other genres of media – tv, film, music videos, video games – do differently to better promote safe sexual messages and highlight less frequently represented identities?

EFR: Pornography is one type of media–it is sexually explicit media. But other forms of media, like TV, film, music videos, and video games can also be guilty of promoting unsafe messages and contributing to our sexual violence problems. And some media content, sexually explicit or otherwise, is A-OK. To me the main point is that we have to talk about pornography because we  have to talk about all media and what it’s doing to our heads. Pornography is no exception. 

TM: What does research in the field of pornography look like currently? Are scholars still uncovering trends behind pornography use or is the focus on education and intervention?

EFR: It’s really only a handful of people who are studying education and intervention compared to a must larger community of researchers who are investigating other things. 

Some are investigating how common pornography use is and whether that has been changing over time. Others are looking at pornography and aggression, or attitudes about violence, or about women. Some study the content of pornography and try to figure out if what we are seeing when we watch pornography is changing over time. Some are studying people’s brains and how brains react to pornography to help us understand what to do for individuals who say that they are compulsive users and want help for that.

TM: If you could use the TEDMED platform to send one message to youth, what would you say?

EFR: Kids:  Pornography is not reality. It’s made to entertain people and to make money, it’s not an instruction manual for having sex. In fact, a lot of the stuff you see is staged, made up, faked, and putting a show for the camera. If you want to have good sex, and be good at sex, you have to talk to your partner. Ask them what they like, what they don’t like, even if that’s awkward. If you can’t talk about it, you shouldn’t be trying it.

TM: What was the TEDMED experience like for you?

EFR: I was really nervous!  It was hard to memorize what I wanted to say. I actually never knew that the TEDMED speakers memorized their talks–it seemed to me that people were speaking off the top of their heads, but now I know the truth.  It was also so much fun, and enriching, and I feel really lucky that I had the chance to do it. 

TM: At TEDMED, we like to think about each talk as having a “gift” — that thing that reveals new perspectives and profoundly influences our own, or our collective, health. What is the gift you’d like people to receive when watching your TEDMED Talk?

EFR: It is OK to feel two ways about something at the same time. Sometimes the answer really is that both sides are right. (For me, I’m worried and upset about the potential that pornography is contributing to violence and misogyny, and at the same time, I think it’s going overboard to denounce all sexually explicit media, wrong to judge people for wanting to see pornography, and antithetical to public health to try to quash sexual freedom).

Massive Science on Sarkis Mazmanian

Massive Science is a digital science media publication that brings together scientists and the science-curious public. The team at Massive joined us at TEDMED 2018 and covered talks by various speakers including Sarkis Mazmanian. Check out their coverage of Sarkis’ TEDMED 2018 talk below.


The jury’s still out on how the brain really works. But Sarkis Mazmanian, a medical microbiologist at Caltech, thinks the answers to many of the questions we still have about the brain may actually lie further south — in the gut, where trillions of bacteria live. There, these “good” bacteria live peacefully, helping us to break down fiber and absorb nutrients. They are referred to collectively as the gut microbiome. Despite the presence of the blood-brain-barrier (BBB), a tightly regulated border between the brain and circulating blood, the gut and the brain are in constant communication, either through incoming and outgoing nerves, or through small molecules that can pass through the BBB. Remarkably, many of these molecules are not produced by the human body — they’re made by the bacteria in our microbiome.

The composition of our gut microbiome is often thought to be established as we pass through the birth canal, and greatly modified through our immediate environment in the first few years of life. After that, the microbiome becomes largely resistant to new bacteria. Interpreting this “gut-brain” axis has been the focus of Mazmanian’s work, revealing complex interactions between the gut and the brain, which increasingly look connected to everything from thoughts and emotions, to potentially the onset of certain brain disorders including Autism Spectrum Disorder and Parkinson’s disease.

Bacteroides fragilis, a common bacteria that occurs in the gut, oblong spheres stained pink.
Bacteroides fragilis. CDC.

You may be wondering a few things. How do trillions of bacteria establish themselves in our gut in the first place? How do our immune systems differentiate between the bacteria that make up our microbiome, and other harmful bacteria that makes us sick? Mazmanian says, “I think our microbiome, having evolved in the context of the immune system, have learnt to co-op with the immune system.” He adds, “Instead of trying to combat or invade the immune system, they actually engage it.” The good bacteria actually have a vested interest in their hosts being able to selectively attack dangerous bacteria, either because the “good” bacteria may also be harmed, either directly, or indirectly if their hosts perish. So, instead of avoiding immune cells, these beneficial bacteria have developed properties which redirects the immune response in a way that doesn’t cripple it. The “good” bacteria are spared, and the immune system is not prevented from attacking other pathogens. In this way, an amicable symbiosis is achieved, in which the gut microbiome is able to thrive in the warm, moist, nutrient-rich intestines. In fact, research carried out by graduate student Gregory Donaldson in Mazmanian’s lab suggests that one microbe in particular, called Bacteroides fragilis, might have even achieved long-term stability in the gut because of an immune response involving an antibody called IgA, which actually helps anchor it to the gut wall.

Mazmanian believes that our microbiome may influence many diseases. A few years ago, Mazmanian and his group noticed that children with autism — a neuropsychiatric disorder where children suffer from behavioral deficits, such as decreased vocalisation and social interaction, as well as repetitive behavior — also experience digestive issues, such as abdominal cramps and bloating. This was a clue that bacteria could be involved in the disease process. Other clues were that risk factors for autism include having a caesarean section, formula feeding, and taking antibiotics in childhood, all of which change the microbiome.

Mazmanian thinks the same may be true of Parkinson’s disease, a neurodegenerative disorder where neurons in the brain die, leading to motor symptoms like tremors, difficultly in walking, and rigidity. Like with autism, Parkinson’s patients often have gut symptoms. Strikingly, 80 percent of the three million people in the U.S. that suffer from Parkinson’s disease also suffer constipation—symptoms that sometimes precede the onset of motor symptoms. Interestingly, people who have had their vagus nerve, a potential highway between the gut and the brain, removed during surgery, are less likely to develop Parkinson’s disease.

 

To study how the gut may influence neurological diseases, Mazmanian completely removed the gut microbiome of mice that are genetically engineered to develop autism or Parkinson’s. He found these mice no longer exhibited symptoms of Parkinson’s or autism, suggesting that the microbiome is involved in both diseases. Mazmanian had stumbled on a remarkable discovery. “When we made these germ-free sterile mice, it gave us a research tool that we can now use for other purposes.” Next, he took fecal samples (which contain intact microbiomes of their donors), from both Parkinson’s patients and healthy controls. He put these samples into bacteria-free sterile mice genetically modified to over-express a protein called α-synuclein (αSyn, which is associated with Parkinson’s disease). The mice implanted with microbiomes from people who had Parkinson’s had much worse symptoms than the mice who received microbiomes from a healthy control. Similarly, when mice with autistic behaviors that had their microbiomes removed were given certain beneficial bacteria recovered from neurotypical humans , Mazmanian’s team were able to reduce their vocalisation deficits and repetitive behaviors.

Of course, these studies have only been carried out in mice, since there are ethical issues with replacing a healthy human’s microbiome with one from a Parkinson’s patient. However, Mazmanian says that dozens of papers have shown that the gut microbiome in autistic people and Parkinson’s patients are different. The cause of these differences — maybe ethnicity, geography, genetics or diet — is unclear, but Mazmanian’s mouse experiments have led him to a provocative hypothesis. He thinks some forms of autism and Parkinson’s may not arise in the brain at all, but in the gut. By targeting the microbiome, in a personalized way, he hopes to develop a viable therapeutic.

It’s not just the gut that sends signals to the brain. Weirdly, the brain also communicates with the gut, although understanding this process has been more challenging. Members of Mazmanian’s lab have been trying to better understand brain –> gut communication by working with neuroscientists using genetic engineering techniques, brain lesion studies, and studying the vagus nerve. Anecdotally, we rely on “gut-feelings” or “gut-instincts” to help us make decisions, sometimes we experience “gut-reactions” in response to an experience, and when we are overcome with anxiety or excitement, we often feel it in in our gut as a stomach-ache or “butterflies.” These turns of phrase suggest what these scientists suspect: that our brains send signals to our gut via our nervous system in response to queues in the environment.

Mazmanian’s lab are trying to not just identify the bacteria that inhabit our guts, but what these bacteria are doing. “We take a reductionist approach in the fact that we work with single organisms we can genetically manipulate,” he says. “I want to manipulate both the bacteria and the host,” isolting each on a molecular level to identify the mechanisms by which they work.

Conversely, Mazmanian likens many traditional drug treatments to pouring oil all over the engine of a car, in the hope that some might get into the right place. He thinks the future of medicine is in “drugs from bugs,” saying, “Someday, you and I may go to the doctor and be prescribed a pill with a live bacteria inside of it as the remedy.”


About the author: Yewande Pearse was born and bred in North London. She is now a Research Fellow based at LA Biomed, in affiliation with the University of California, Los Angeles (UCLA). She completed her PhD in Neuroscience at the Institute of Psychiatry in 2016, which focused on the potential use of gene therapy for the treatment of Batten disease, a fatal neurological pediatric disease. She is now working on stem cell gene therapy using CRISPR-Cas9 to treat Sanfilippo Syndrome. Before completing her PhD, she worked in the areas of Stroke and Huntington’s disease research and also worked in a care capacity, with people living with Autism, suicidal ideation, dementia and HIV Associated Neurocognitive Disorder.

The TEDMED Research Scholars are a carefully selected group of passionate and objective individuals whose expertise spans the biomedical, public health, and emerging technology spectrums. Every year, Research Scholars help us to vet the science and timeliness of our TEDMED Speaker nominations, allowing us to better examine the diverse nominations we receive.

This year, we have selected 50 Research Scholars with unique backgrounds and areas of expertise. The TEDMED 2020 Research Scholars represent organizations and institutions including the Brigham and Women’s Hospital, Johns Hopkins University, UnitedHealth Group, University of Toronto, Humana, the Massachusetts Institute of Technology, and so much more, including Massive Science.

We’re excited to once again partner with Massive, a digital science media publication that brings together scientists and the science-curious public, and tap into their pool of first-rate researchers to help us evaluate this year’s nominations. The TEDMED-Massive Scholars are members of TEDMED’s 2020 Research Scholars Program, and they are denoted by an asterisk in the list below.

We are honored to announce this year’s TEDMED Research Scholars, and we thank them for their generous contribution of time and expertise. Many will join us at TEDMED 2020 and we hope you will meet them there. As a reminder, early bird registration is still open, so register for TEDMED 2020 today!

TEDMED 2020 RESEARCH SCHOLARS:


*TEDMED-Massive Scholar
Learn more about Massive at massivesci.com/

Abe Janis, MS
Regenerative Medicine, Medical Devices, Skin Injury & Healing

Alex Lopez, MS, MD
Healthcare, Medical Technology, Basic & Clinical Research, Augmented Reality, Education

Alexandrea K. Ramnarine, BS
Infectious Diseases, Nanotechnology, Regenerative Medicine

*Alyssa Shepard, PhD Candidate
Cancer Biology, Molecular Biology

Andrew Chou, MD,
Orthopaedics, Biodesign, Medical Devices, Education

Beth Taylor Mack, PhD
Health and Wellness Innovation

Bhanu Ghantasala, MSc
AI / Emerging Technologies, Digital Health Entrepreneurship, Patient-Centric Innovation

Biodun Awosusi, MD, MSc
Health Economics, Health System Innovation, Digital Health

Brendan Brbich, MSc
Public Health (Health Economics)

*Brittney G. Borowiec, PhD Candidate
Comparative Physiology, Zoology, Science Writing

Daniel Bu, MD/MSc Candidate
Behavioral Economics, Global Health, Health Care Delivery

Darren Saunders, PhD
Molecular Oncology, Neurodegeneration

*Devang Mehta, PhD
Genomics and Genetic Engineering of Plants

Elena Minenko, MS
Pharmaceutical Industry, Neuroscience, Health Informatics

Elizabeth W. Mwashuma, MSc, PhD Candidate
Public Health Informatics, Implementation Research

Evan Yates, DO, MBA, MSc
Osteopathic Medicine/ Genetics

Fahima Dossa, BSc, MD, PhD Candidate
Clinical Epidemiology, Health Services Research

Fidaul Alam, MD
Medical Education, Clinical Research, Health Advocacy, Neuroscience

Frank Qian, MPH, MD Candidate
Cardiovascular Medicine, Cancer Epidemiology, Population Health

Jessica Dale, BSHM, MSN, CCFP, CTP DNP
Compassion, Compassion Fatigue, Burnout, Grief, Care Delivery

*Jiwandeep Kohli, PhD Candidate
Neuroscience and Clinical Psychology

*Joshua Peters, PhD Candidate
Bioengineering, Genomics, Infectious Disease, Immunology

Kaitlyn N. Sadtler, PhD
Immunology & Regenerative Medicine

Kanupriya Agarwal, MD, MBBS
Physician Entrepreneur, Digital Health, Precision Oncology

Kelly Jamieson Thomas, MS, PhD
Cancer Prevention, Wellness Education

Kyle Isaacson, PhD
Bioengineering

*Lauren White, Post-doc, PhD
Disease ecology

Mari Teitelbaum, MHA
Maternal-child health, Health information Systems, Strategic Perspectives, Health Outcomes, Innovation

Martin Jensen, PhD
Bioengineering, Emphasis in Biomaterials

Meg Barron, MBA
Digital Health, Healthcare Innovation

*Monica Javidnia, PhD
Neuroscience, Neurodegenerative Disease, Pharmacology

Nicholas A. Giordano, PhD, RN, AM, MS, BSN
Pain Science

Oyuka Byambasuren, MD, MMedRes
Digital Health, mHealth, Primary Care, Health Apps

*Pallavi Pant, PhD
Air Pollution, Environmental Health, Science Communication

Paul Lindberg, JD
Public Health, Community Health

Peter A. DePergola II, PhD, MTS
Clinical Bioethics and Medical Humanities

Pooja Chandrashekar, MD Candidate
Healthcare Delivery, Digital Health, Population Health

Rachel Rizal, MD
Healthcare Innovation, Digital Health, Entrepreneurship, Health Education

Ria Rungta, MPH Candidate
Epidemiology, Global Health, Chronic Diseases, Genetics, Health Technology

Sara Jiayang Li, BS
Autoimmune Skin Disease, Clinical Research

sj Miller, PhD
Gender Identity in Schooling Contexts

*Sophie Okolo, Ms, MPH
Aging, Health Technology, Bioinformatics, Science Communication

Stephen Chen, MD, PhD
Surgery, Genomics, Oncology, Biotech & Life Sciences

*Tara Fernandez, PhD
Cell & Gene Therapies

Tareq Al Saadi, MD
Medicine, Epidemiology, Public Health, Cardiology

Toyosi Okurounmu, MD, MPH, MBA
Health System Transformation

Victor Ekuta, BA, MD Candidate
Neuroscience, Neurodegenerative Disease, Neuroimaging

Vivian Ho, MBA
Global Health, Medical Innovation, Neuroscience

*Xinwen Zhu, PhD Candidate
Biotechnology, Systems Cell Biology

Xiya Ma, MSc, MD Candidate
Global Health, Biomedical Research, Innovation

Jason Shepherd on Scientific Discovery

Taking on the major challenge of understanding how experience shapes neural networks and how circuits are modified by proteins/genes,  Jason Shepherd has garnered worldwide recognition through the research in his lab, Shepherd Lab at the University of Utah School of Medicine. At TEDMED 2018, Jason shared why we might have viruses to thank for the biology behind memory storage and encoding. Watch his Talk “How an ancient virus spread the ability to remember” and read his about his journey through Scientific Discovery below. 


What goes into scientific discoveries? Movies will have you think that discoveries are made by lone geniuses in moments of inspiration. The reality is that this is rarely the case, scientific discovery is a long and often tedious process that requires a team of people. In my own research lab, we recently made a surprising connection between two seemingly unrelated topics; viruses and memory. 

This connection was made through observation, rather than through inspiration. We study a gene called Arc, which is essential for making long-lasting memories in the brain. A focus of my lab is to understand how and why this gene is so important for information storage. A technician in the lab, Nate Yoder, wanted to study the biochemistry of Arc protein. To do this, we engineered bacteria to produce a ton of Arc protein that we could purify. Nate found, however, that Arc protein behaved strangely. It seemed like it was much bigger than predicted and this was probably because single Arc proteins were clumping or aggregating. Perhaps we were just unable to purify Arc properly. Still, Nate was curious to know what the protein looked like so with the help of Adam Frost he took some images of Arc protein using an electron microscope. This allowed him to resolve Arc protein at very high magnification. Strikingly, instead of clumps of protein, we saw these beautiful “soccer ball” structures (image 1). 

This observation led us down a rabbit hole of unique biology. Turns out these soccer ball structures look just like the protein shells or capsids that viruses make. Why would a neuronal protein form something that looks like a virus capsid?! We are still trying to understand this surprising discovery, but Arc seems to have retained many properties of viruses. Oh yes, and we think that this gene evolved from an ancient ancestor of the retroviruses, like HIV, called retrotransposons. These rogue elements, along with ancient viral infections have left us with bloated genomes comprising of up to 50% of our own human DNA. In some cases, it seems, evolution has used these sequences and repurposed them to create new genes. Wild! 

Back to the process of doing science. Another common fallacy is that science results in black and white answers. In biology, this is rare. Scientists can be wrong in their interpretation of the data. They can be wrong in how they designed an experiment and the results can be messy. The key is replication and figuring out many different ways to get at the answer. For example, another lab headed by Vivian Budnik and work led by her postdoctoral fellow Travis Thomson independently found that a gene that looked like Arc in the fly, also seemed to behave like a virus. When we purified the fly Arc protein, we also saw that it could form capsids. So here we have two examples of different genes having retained the ability to form virus-like capsids! Even more surprising, we think that the fly Arc gene is actually unrelated to the mammalian gene; evolution repurposed a similar kind of retrotransposon in the fly lineage 100s of millions of years after the mammalian Arc gene.

If it happened twice, it probably happened many times more. We and others are on the hunt to find other genes that may have similar properties. Most important for my own research, we want to understand why you need a virus-like protein to make long-term memories. All of this reinforces, to me, the intricate and complicated path evolution has taken that has led to the amazing structure of the human brain. We hope that this science will not only lead to understanding how the brain works, but potentially to applications like gene therapy. Currently, we rely on modified viruses to get gene therapy into human cells but these still elicit an immune response and are often not very efficient. What if we could use proteins that look like viruses but are already made in our bodies? Nature often has the best solutions to hard problems; we just have to figure out how. It takes a team of dedicated people and a little bit of luck to reveal Nature’s secrets. 


TEDMED & Massive Science: TEDMED boasts a proud partnership with Massive Science, a digital science media publication that brings together scientists and the science-curious public. The team at Massive joined us onsite at TEDMED 2018, and by various speakers including Jason Shepherd. Check out their coverage of Jason’s TEDMED 2018 talk: “A protein in your brain behaves like a virus, infecting your cells with memories.

Massive Science on Lydia Bourouiba

TEDMED is proud to partner with Massive Science, a digital science media publication that brings together scientists and the science-curious public. The team at Massive joined us onsite at TEDMED 2018, and covered talks by various speakers including Lydia Bourouiba. Check out their coverage of Lydia’s TEDMED 2018 talk below.


In 1934, Williams Wells was the first scientist to convincingly describe airborne transmission of diseases in the context of tuberculosis. He introduced the notion of  two main routes of pathogens spread: large droplets, which fall due to gravity, and small droplets, which waft through the air as they evaporate. It is believed that pathogens like Tuberculosis are transmitted through large droplets, whereas diseases like measles could through small ones, although evidence remain controversial and debated. 

It may surprise you that for more than 80 years—despite new diseases, new means of travel, and new technology—our understanding of these basic routes haven’t changed much. Not until recently, when Lydia Bourouiba, associate professor at the Massachusetts Institute of Technology and director of the Fluid Dynamics of Disease Transmission Laboratory, began to revisit these fundamentals and redefine how we think about respiratory disease transmission—literally from the ground up.

Bourouiba began her career by studying the mathematics of how fluids flow, specifically looking at fluids with turbulent or chaotic dynamics/motion. When she moved to Toronto shortly after the SARS epidemic, she realized that similar mathematical principles could be useful in modeling how diseases spread. That’s when she began to use mathematics in epidemiology, and in particular, the limitations of top-down modeling with mechanistic understanding of the fundamental mechanisms governing the patterns observed. “I started seeing these gaps in understanding transmission in particular, and [seeing] that fluid dynamics could help fill such gaps,” explains Bourouiba.

Traditionally, scientists have created epidemiological models by developing equations, based on a variety of parameters that describe how diseases are transmitted between people and populations. However, many of these parameters are fitted to data and not based on physical principles—like how sneezing actually transmits disease, or what factors influence how far sneeze droplets may travel or persist. 

Bourouiba thinks that improving the accuracy of these parameters and framework of modeling would greatly improve predictive power and intervention strategies. “If one doesn’t have a mechanism to rationalize [the parameters] down to something we can directly measure, validate, and control, one ends up fitting data to models,” says Bourouiba, rather than designing models that incorporate underlaying physics. “One loses predictability power and ability to control.”

So Bourouiba moved to MIT as an NSERC Postdoctoral Fellow and Applied Mathematics Instructor, and then as faculty, and began to try to explain how diseases are transmitted globally based on how they are transmitted between you and your neighbor. Equipped with a range of experimental optical and biophysics methods, including, direct visualization and measurements, such as with high-speed imaging, microscopy, fluid flow models, and patients, Bourouiba and her team are now answering fundamental questions about the mechanisms of respiratory disease transmission.

During TEDMED, Bourouiba showed how the physics of turbulent puff cloud of air emitted during exhalations, suspending and trapping drops within them, radically  change the range of pathogen deposition and contamination, thus, shifting the paradigm away from the small versus large droplet framework of Wells into the mechanistic description of exhalations including information of time and space, needed for monitoring, infection control and prevention,  and risk assessments. 

The next step is understanding how a exhalations coupled with ambient environment and patient physiology in infection, including when infected with flu, can inform early detection and intervention.  Her broad findings have already identified suggestions for disease control that can be implemented, influencing a variety of public health protocols and policies.

But she still has further questions—like how the size of droplets can impact our susceptibility to disease. “The properties that exhalations and their payload influence also efficacy of infection upon exposure, for example influencing,  their deposition in the lungs,” says Bourouiba. “We are working at elucidating the whole process, accounting for coupled physiology, immunology, microbiology, and fluid processes, to construct the full picture of those  that have particularly high abilities to transmit certain respiratory diseases effectively.”

This could inform how we manage numerous high impact pathogens. Take tuberculosis, a disease that infects up to a third of the world’s population. Researchers know its symptoms begin deep in the lungs, but further characterizations of when, how, and why people produce infectious droplets could improve how we handle patient care and research.

Bourouiba is excited about the multi-year study she’s leading with a diverse collaborations she put in place to  include clinicians, infection control specialists, microbiologists, immunologists, and virologists, for the study of transmission of influenza. Pioneering work in this interdisciplinary field isn’t easy. But Bourouiba says that ten to twenty years of this kind of research could lead to dramatic, tangible results, useful for a variety of pathogens. Considering the long and often uncertain process of developing new vaccines and diagnostics for infectious diseases, her approach to defining evidence-based prevention strategies is a vital piece of the puzzle. “You have to be doing both [prevention and treatment research].” It’s also becoming ever more important. Because of rising antibiotic resistance and increase in connectivity, and emergence and re-emergence of pathogens, she explains, “We might be going into an era [similiar] to pre-antibiotic times, which is extremely concerning.”

Bourouiba’s work is an important step toward redefining disease transmission, and infection control and prevention, moving the fundamentals from descriptions to measurable and quantifiable mechanisms. Truly understanding how people get each other sick will help us design protocols, policies, and tools to help people stay healthy and prevent epidemics and pandemics.


About the author:  Joshua Peters is a PhD student in Biological Engineering at MIT. Around two billion people in the world are infected with a microscopic bug called Mycobacterium Tuberculosis. Despite this, only a fraction develop tuberculosis. And a fraction of those infected – almost 5,000 a day – die. Joshua puts on Stranger Things-esque protection equipment and probes these bacteria to ask, what allows them bacteria to win this tug-of-war? To understand this variation, he looks at how both human and bacteria cells change on a genetic level in response to each other, as a member of the Blainey Lab, located in the Broad Institute, and Bryson Lab, located in the Ragon Institute and MIT.