Programming Cures with Synthetic Biology

Tim Lu uses his extensive background in computer programming, electrical engineering and micrcobiology to engineer cells to act as living therapeutics. At TEDMED 2018, Tim Lu shared how his work in bioengineered medicine is enabling dynamic responses to disease in previously unseen ways. Watch his Talk, “Biological engineering—the nexus between computer programming and medicine” and read his post below to learn more about his pioneering work.


Ever since the human genome was decoded, we’ve gained considerable insights into the origins of disease. The biological programs encoded by the DNA inside our cells are highly interconnected, allowing them to orchestrate the complex activities of life. When these fine-tuned interconnections within cells and between cells go awry, disease results.

With an increasing understanding of these dysfunctional biological programs and their role in human illness, scientists are trying to develop new ways to cure disease, not simply keep it at bay. However, our current armamentarium of medicines is dominated by small-molecule drugs and biologics, such as antibodies and enzymes. Although these medicines have resulted in tremendous advancements in human health, they are fundamentally limited in their activity and are nowhere as sophisticated as the disease networks they are trying to address.

For example, these drugs distribute systemically throughout the body and are not easily activated (if more activity is needed) or suppressed (if side effects are encountered). In addition, these medicines often only target a single mechanism of action, which may be insufficient to cure diseases. The basic problem is that we are using static, simple, non-living medicines to treat indications that are inherently dynamic, multi-factorial and living.

Fortunately, while we’ve been decoding our DNA and the biological programs we’re born with, we’ve also been learning how to design DNA to create new programs in living cells. The engineering discipline of synthetic biology has the potential to create powerful new medicines that can match the complexity of disease with even more sophisticated therapeutic programs. These medicines are called (1) cell therapies, where living cells are reprogrammed with artificial DNA programs and delivered into patients, and (2) gene therapies, where the artificial DNA programs are administered directly into patients, typically using a virus or a chemical carrier.

We’re already seeing these living cell and gene therapies have an impact on certain diseases, such as acute lymphoblastic leukemia (ALL). For example, a new class of medicines called CAR-T cells are made by extracting T cells from ALL patients, engineering them to kill any cells expressing a protein called CD19, and then reinfusing the living drug into the body, wherein the CAR-T cells eliminate CD19-positive leukemia cells, as well as normal B cells. These CD19-targeting CAR-T cells have achieved tremendous success in the clinic, with more than 80 percent complete response rates in some studies.

However, we’re only scratching the surface of what is possible with current cell and gene therapies. For example, CAR-T cells don’t work particularly well against solid tumors, such as ovarian, lung and liver cancers, or difficult-to-treat liquid tumors, such as acute myeloid leukemia (AML). Solid tumors have evolved multiple ways to block T cells from being active within the tumors, so that CAR-T cells can’t exert maximal killing activity against cancer cells.

More sophisticated genetic programming through synthetic biology can help overcome this challenge. For example, CAR-T cells can be engineered not only to kill cancer cells, but also to secrete multiple additional drugs that counteract solid tumor defenses in a multi-factorial fashion. Combination therapy encoded within a living cell therapy can address the complexity of cancer disease networks and significantly improve treatment effectiveness.

Moreover, diseases, such as AML, are highly heterogeneous, so that it’s difficult to find a single antigen target that can discriminate between cancer and healthy cells. Antibodies and CAR-T cells that only go after a single target can generate significant side effects by also killing healthy cells. This isn’t a major problem with CD19-targeting therapies in ALL, because people can survive ablation of all their healthy B cells (which make antibodies) by being supplemented with antibody infusions. However, when the healthy tissues that are inadvertently killed are irreplaceable — such as stem cells, cardiac tissue or lung cells — these side effects can cause substantial toxicity.

Fortunately, we no longer have to be satisfied with drugs that only rely on a single protein to distinguish between diseased and healthy cells. Leveraging synthetic biology, we can design cell therapies to sense multiple disease biomarkers and to respond only when a specific combination of biomarkers is encountered. For example, CAR-T cells can be outfitted with a “NOT gate” program to kill tumors when they express biomarker A but NOT biomarker B, and to prevent killing of healthy tissues that express both biomarker A and B. By doing so, we can significantly increase the safety margin of these drugs and enable enhanced potency against cancer cells.

These biological programs are just a few examples of how programming sophisticated living drugs can improve therapeutic outcomes. The emerging synthetic biology toolbox also enables living medicines that can be turned on or off by administering orally dosed FDA-approved small molecule drugs. Such medicines can be narrowly targeted against specific cell types or tissues, and that can even adapt their activity to dynamic and evolving diseases. A new era of programmable drugs is coming, and has the promise to deliver cures that match the complexity of human diseases.

Massive Science on Kathleen O’Donnell

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 Kathleen O’Donnell. Check out their coverage of O’Donnell’s 2018 TEDMED Talk below.


Photo Courtesy of Massive Science

There’s been a bevy of heavy metal, superpower-imbuing robotic suits in pop culture — think Halo, Avatar, or Iron Man. In fact, these fictional portrayals were what inspired researchers at Harvard’s Wyss Institute in the Biodesign Lab to develop a new exosuit.

Initially, the goal of the exosuit project was to develop military applications. (Not surprising, considering the project was funded primarily through DARPA.) The researchers combined traditional robotics with flexible fabrics and lightweight parts, resulting in a soft, wearable design.

The scientists realized this technology could also be a medical tool. Kathleen O’Donnell, a staff industrial designer at Harvard’s Wyss Institute, met with clinicians and quickly honed in on stroke patients, who often suffer from weakness and loss of control in one side of their body. O’Donnell’s team envisioned designing a suit that could be attached around the waist and calf, to help stroke patients balance their strides, reducing the effort it takes to walk. Volunteers were soon recruited as study participants, and a team of roboticists, industrial designers, control engineers, and physical therapists began designing, testing, and iterating the suit.

The team quickly faced several major challenges. “We have algorithms that measure the way you walk and try to predict when are you taking a step so that we can time the assistance,” explains O’Donnell. This kind of responsive assistance was easy to control in soldiers, since they tend to walk with symmetric, regularly-paced strides. But stroke patients tend to walk with different compensations and irregularities.

“Her foot looked so much more confident, so much more stable. She was able to stand up straighter.”

“Everybody walks a little bit differently after their stroke. They have different compensations they may use. One person might hike their hip up as they’re walking. One person may swing their leg around as they’re walking,” says O’Donnell. “We had to understand how to ignore [the compensations] to some extent, but still get the information that we needed about their gait to time the assistance with their particular gait pattern.” This personalized capability required the team to build adaptable algorithms that adjust the suit’s required assistance with every step. The resulting exosuit never imposes how to walk — it just helps the patient walk naturally.

Another major difference between soldiers and stroke patients is body type. While it’s easier to design for the typically fit physiques of soldiers, stroke patients’ physiques vary widely. Since the suits need to attach closely to a patient’s body, individual body types can significantly change the design of the suit. O’Donnell explains, “From an apparel design side, understanding both the range and mechanisms we were using to attach [the exosuit] as securely as possible to the patients became more challenging.”

With a diverse group of patients, the team built a toolbox of strategies to individually fit an exosuit to every user. During one testing and recording with a patient, O’Donnell describes the patient’s transformation as dramatic. “Her foot looked so much more confident, so much more stable. She was able to stand up straighter.” While she acknowledges that fitting the suit required time, even without any optimization, the change in patients was frequently instantaneous.

From the beginning, O’Donnell and her team focused on patient volunteers who had experienced strokes and could immediately benefit from the exosuit. “It has been such an amazing process to work with all these volunteers from the community,” says O’Donnell. “Our first volunteer is still one of the volunteers who comes in, five years later.” Licensing the technology from the Wyss Institute, O’Donnell guided the transition of the exosuit and began to manage clinical trials in the hopes of making the suit available to the millions of stroke patients in the United States today.

“We are starting in stroke, but we could potentially see suits for MS or suits for Parkinson’s.”

So far, the exosuit has been tested on more than 40 patients. Of course, there will be potential challenges in scaling the technology. “We have made as much of an effort as possible to get as diverse a range of patients as we can. That includes body sizes and types, walking speeds, [and the] types of assistive devices they use,” O’Donnell says.

Giving freedom back to stroke patients is just the beginning. O’Donnell says the exosuit could help many other kinds of patients too. Other injuries or disorders are also on their minds. “We are starting in stroke, but we could potentially see suits for MS [multiple sclerosis] or suits for Parkinson’s.” With the ability to quickly alter and control the assistance, the exosuits could help people undergoing physical therapy by providing assistance when needed and taking it away to help rebuild strength. On the other side of the spectrum, the exosuit could be used at home to provide general, consistent assistance. Luckily, being made out of fabric helps reduce the overall cost of the exosuit. The possibilities for exosuits in medicine will be exciting to watch.


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. He 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.

Christine Nieves on Community

After Hurricane Maria decimated the physical and material infrastructure of the island of Puerto Rico, Christine Nieves began to mobilize what could not be destroyed, the community. At TEDMED 2018, Christine shared the importance of community and how she and her team are finding ways to support healing from individual and collective trauma. Watch her Talk, “Why Community is our best chance for survival—a lesson post-Hurricane Maria” and read her blog post below to learn about her new venture, Emerge Puerto Rico (EmergePR) and why she is working to pioneer community-based climate change education and leadership.

Growing up, I didn’t see Puerto Rican figures as examples of leaders, visionaries, or doers that I could call role models. Through the radio, news, neighborhood and social gatherings, I learned that we just weren’t capable of solving our problems, running our island, or frankly, being accountable for anything. “Without America,” I heard repeated over and over again, “we will not have jobs, or food, or funds for public services.” I also learned that nothing good could ever happen in Puerto Rico; so why even try? This idea became an unquestionable truth for me. When I left Puerto Rico for college, I carried a mix of conspicuous pride for being Puertorriqueña and a disdain towards Puerto Rico, my mainland. People in Puerto Rico, I heard around me, were lazy, and just wanted things done easy, and then we had corruption throughout government and corporations making it difficult to be on the island if you were a regular hard-working family. Life for everyone around me was a constant survival struggle. I didn’t feel I had options, so I left the island, and promised to never come back.

Photo Credit: Christine Nieves

Why I returned and how my view of Puerto Rico changed forever is what I go into detail in my talk. And while Hurricane Maria was my catalyst for this chapter, just this summer we had another Hurricane-level event: a historic million people 12-day protest that culminated in our highest-ranking elected official being forced to resign. Just like after Hurricane Maria, this summer the message was crystal clear: we, Puerto Ricans, have been believing a story about ourselves that is not true and when everything collapsed, when our leaders failed us, our true nature emerged. What we accomplished this summer and after Maria is more than a lesson about Puerto Ricans, it is a sobering truth about the greatness waiting on the other side of liberation. Liberation from our own ideas about our history, humanity and what we are capable of.

Volunteer board in Puerto Rico post-Hurricane Maria.
Photo Credit: Ricardo Alcaraz

On Sept 20, 2017, the world changed for me, and for the 3.5 million Puerto Ricans living on the archipelago. Our home was flooded and my husband and I lost almost all of our furniture, clothes, books, technology—we’re still recovering! —but out of this devastation, we decided we needed to do something. And to our surprise, that something would turn into Proyecto de Apoyo Mutuo Mariana (PAM): a fully community-driven disaster response and recovery effort: kitchen, aid distribution, food delivery, arts, culture and recreation activities for kids, and a full transformation towards renewable energy sources, rain-water catchment systems, filters installed in natural water sources through the mountain, even solar-powered Wi-Fi and satellite communication. While in the midst of doing, we spent a lot of time reflecting on this question: How can our community (a so-called marginalized community) support human adaptation to a changing climate?

Now we face a unifying threat for humanity – our changing climate. And because Puerto Rico is an archipelago, our islands are living the future, NOW. Through Emerge Puerto Rico (EmergePR), our new venture, we are ringing a clarion call for harnessing wonder, awe and imagination as the birthplace of powerful community-based adaptations to climate change. In so doing we are moving beyond from fear, shame and guilt, towards the concrete examples that challenge our notions of what so-called marginal communities are capable of.

Puerto Rico, as it turns out, is bursting with audacious endeavors that are getting world-wide acclaim and our role at EmergePR is to make it impossible to ignore initiatives like PAM that every day become stronger all over our islands. When ALL of our attention and energy is placed on the inspiring history-bending and counter-narrative examples of human greatness we can begin to transform our future.

If you haven’t been to Puerto Rico, come see for yourself.

Massive Science on Christine Nieves

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 Christine Nieves. Check out their coverage of Nieves’ TEDMED 2018 Talk below.


As storms become more severe and more frequent, people around the world will need to get better at recovering from disasters. After Hurricane Maria struck in September 2017, for example, Puerto Ricans had to become experts in disaster recovery overnight. One such newly-minted authority is Christine Nieves, who has a vision of apoyo mutuo, or mutual aid.

Nieves left Puerto Rico when she was 18, after spending years feeling trapped on the island. She finished her education at UPenn and Oxford, but while living in the mainland United States, she realized that she didn’t have a sense of community. So she decided to return home, just a few months before Hurricane Maria made landfall.

Nieves remembers telling her mother, “I’m ready! We’re going to be fine”

Nieves now lives in a small, mountainous community in Puerto Rico called Mariana. She wasn’t concerned when she heard that a hurricane was on its way. “We didn’t know what was coming,” she said. Nieves remembers telling her mother, “I’m ready! We’re going to be fine,” — but the storm was much more destructive than expected.

After the worst of the hurricane was over, Nieves and her neighbors were in rough shape: Like most of the island’s towns and cities, there was no electricity, no running water, and no cell phone service. People in Mariana knew that because of their isolated location, it would take days for government aid to reach them, so they took matters into their own hands.

Image by erikawg from Pixabay

Nieves and her partner decided to start a community kitchen. They got permission to use an industrial kitchen space. Finding food and cooks was a little bit harder than they anticipated, at least at first. Immediately after the hurricane, it was difficult or impossible to call anyone, so they had to go door to door to contact people. “When everything collapsed, there was a different system left,” Nieves said. That effort made Nieves realize how reliant they had been on phones and the internet. “We need to really strengthen and understand how our infrastructure is fragile. But at the same time, we need to create systems that are not fragile, and not tech-related,” Nieves said.

She asked people, “What do you love to do? Do you want to come and join us?” Nieves ended up with a small team of local residents who had been hit hard by the storm, but still wanted to help. People contributed whatever they could, from beans to vegetables to bags of rice. Young people brought hot food to elderly neighbors. By the end of the week, the community kitchen was feeding 300 people every day. Even more importantly, everyone had a job to do.

Community-based mutual support is totally different from how disaster recovery is usually approached.

In some ways, this may sound like an idealistic community of preppers. But instead of an individual person building up a cache of canned food and guns so they can hole up and wait out a disaster, Nieves says that mutual support brings communities together.

Community-based mutual support is totally different from how disaster recovery is usually approached. In many places, including parts of Puerto Rico, disaster survivors eat government-provided MREs (Meals, Ready to Eat) and wait in long lines to receive water or charge their phone. That’s not to say they don’t want to do anything, but sometimes all there is to do is wait.

In Nieves’ model, mutual aid allows community members play an active role in the survival and rebuilding process. It’s not a new concept, but it’s one that was necessary in Mariana: Government officials didn’t reach Nieves’ community until 12 days after the storm subsided.

Nieves pointed out that once help arrived, there was an additional layer of complication: many of her neighbors don’t read English, so they were unable to understand the directions on the MREs that were distributed. They ended up eating them cold or without knowing what they contained.

Photo by Quaid Lagan on Unsplash

So, even after some aid started coming in, the community kitchen continued. “Being able to eat something vibrant that was cooked with love transmits hope. We saw the difference between big operations that were giving you just enough food so that you wouldn’t die, and the abuelas [grandmothers] who were going to give you a big plate so that you would be full and nourished for the whole day, with a smile.”

Mariana spent nine months without electricity from the grid, and six without water. Even now, it isn’t back to anything resembling normal. “There are a lot of blackouts, so there is a constant state of not knowing if you’re going to need gas for your generator. You don’t know if your food is going to rot. If you depend on electricity for oxygen, dialysis, anything … good luck,” Nieves told me.

Still, Nieves has hope that the lessons her community learned after Maria will help other towns in the future. “We believe that this is a model, or at least a series of ingredients, that every community needs to have if they’re going to survive,” she told me. “Communities are our best chance at adapting. Together we might be able to create more.”

If you’d like to support mutual aid in Puerto Rico, you can make a donation here and read more about Nieves’ work here.


About the author: Gabriela Serrato Marks is a PhD candidate in marine geology at MIT. She uses stalagmites to create past climate records that provide context for future climate change.

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. healthcare 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).