Fundamental American principles of freedom and justice are at the heart of an unsettling film that was screened at Harvard on May 4.“The Response,” a 30-minute work created by actor, producer, and lawyer Sig Libowitz, is based on transcripts from military tribunals held at the Guantanamo Bay detention camp in Cuba, which at one point housed more than 700 people suspected of having links to terrorism. The tribunals were established to determine whether detainees had been correctly classified as “enemy combatants.”In the film, Aasif Mandvi, an actor known largely for his comic work on “The Daily Show,” gives a disturbing performance as a man held for four years because of suspected connections to the terrorist group al-Qaeda. Tight camera shots of Mandvi’s face add to the drama of a tense courtroom scene as he pleads his innocence before three military officials who repeatedly question him about evidence he is forbidden to see.The officials deliberate Mandvi’s fate in the following scene. A heated exchange between two of the three military officers, a Colonel Simms, played by Kate Mulgrew, and a Colonel Jefferson, played by Peter Riegert, highlights the film’s underlying dilemma.“Are you willing to keep him locked up based on suspect evidence he can’t even hear? If we are fighting an ideological war, shouldn’t we be holding on to an idea worth fighting for, say, like the Constitution on the rule of law?” Jefferson asks.Wary of letting a potential terrorist walk away, Simms responds, “We are compelled to make the best decision we can under the laws we were given. Obviously it’s not a perfect solution.”It is left to Libowitz, a conflicted Captain Miller, to cast the deciding vote. The film ends, and it’s left to the audience to decide which choice he makes.The screening at Boylston Hall’s Fong Auditorium and following panel discussion were sponsored by the Humanities Center at Harvard.The status of such detainees is “troublesome from the human rights perspective,” said Jacqueline Bhabha, executive director of the Harvard University Committee on Human Rights Studies and the Jeremiah Smith Jr. Lecturer in Law, who moderated the panel.The film, said Bhabha, reveals how a complex situation can fall “prey to prejudice and emotion,” in the absence of any clear rules.At the heart of “The Response” are profound questions about the U.S. justice system in the aftermath of the 9/11 attacks. With its narrative, the film asks its audience to consider what course of action is fair and just during a war on terror; what kinds of restrictions to civil liberties and human rights are acceptable when it comes to national security; and if information gained during interrogations involving torture can be considered reliable.It was at the University of Maryland School of Law, where Libowitz was taking a class on homeland security and the law of counterterrorism, that he first read the military transcripts that took his breath away.“I just knew I had to learn more,” he, said, adding that as he dug into the research he also quickly realized “there was a film there.”Upon completing the film, Riegert said he understood how much he took his freedoms and the American system of law for granted.“I have come to appreciate how little I investigated what American law is and how crucial habeas corpus is to the definition” of the United States.The question of whether or not to give the detainees habeas corpus — a legal standing allowing a detainee to appear in court before a judge to determine whether he or she has been lawfully imprisoned — has become a dizzying juggling act among the Congress, the Supreme Court, and the sitting president since detainees first were sent to the camp in 2002. Ultimately, a 2008 Supreme Court ruling held that the Guantanamo Bay detainees should be granted access to the U.S. judicial system.“Stage one was no process, stage two was the sort of kangaroo proceeding that you saw [in the film], stage three is habeas corpus judicial review proceedings in Washington, D.C., before independent federal judges,” said panelist David Cole, professor of law at Georgetown University.Of the 40 or so such cases that have reached conclusion in the third stage, 75 percent of the time the judges have ruled there is “insufficient evidence to conclude that these individuals are enemy combatants and have ordered them released,” said Cole.“That’s a pretty remarkable statistic,” Cole added, arguing that the convoluted process involving the detainees has resulted in two major costs for the United States.The first, he said, as depicted in the film, is the cost of torture.“When you employ coercive tactics to get information from people, as we did at Guantanamo, you taint that information forevermore.”Cole said the second cost was the approach, taken by the Bush administration, that “going forward, the law will play no part in what you do.”He called the film “critically important” in helping the American people examine whether the last eight years reflected tough, justifiable decisions, or illegal, immoral actions.Panelist Noah Feldman said the film can’t be considered a tragedy in the classic sense because it “sets up a possibility of a structure of horror followed by resolution,” where American systems of justice (or in this case Libowitz’s character, Captain Miller) do the right thing. But the picture in the real world, he said, makes him decidedly more nervous.“My nervousness in the real world,” said Feldman, who is Harvard Law School’s Bemis Professor of International Law, “is about the question of what’s next?”Even if President Barack Obama is able to keep his campaign promise and close Guantanamo, “We are still stuck with the problem of what to do with people who allegedly … are connected to an organization or set of organizations that see themselves more or less at war with the United States,” said Feldman.For Libowitz, the film, which has screened at college campuses, the Pentagon, and the Department of Justice, asks audiences to ponder how to find a balance between national security and civil liberties.“Where we decide we are — what that balance point is — is who we are as a country. I think that is something that everyone has to answer.”
While in Houghton Library, sorting through stacks of old manuscripts and letters from the great naturalist Charles Darwin, history of science graduate student Myrna Perez and lecturer Alistair Sponsel stumbled across something extraordinary: a previously unknown letter from Darwin to his colleague and later nemesis, zoologist Richard Owen.“We initially went [to Houghton] to confirm that a few letters we thought were here at Harvard were actually here,” said Sponsel, who, like Perez, is an affiliate of the Darwin Correspondence Project, whose American editorial office is at Harvard.“We were not really looking for a new letter,” Perez said. “One of the editors … noticed there were some discrepancies between the letters that the project believed to be at Harvard, and what she could tell from the Harvard catalogs themselves.”After cross-checking the British lists and the Harvard catalog, Perez came across a letter that couldn’t be found on any of the lists.“I was a little excited, but a bit skeptical that it would actually be new,” she said. “And then when I got it, I spent a long time looking through our project databases, had Alistair check what I did, and we finally concluded that it was a letter unknown to the project.”According to Sponsel, Darwin wrote the undated letter in April 1848, long before his landmark book “On the Origin of Species” was published. Darwin would have been 39 years old, but he was already famous as a voyager and author. Owen had previously contributed to Darwin’s book “The Zoology of the Voyage of the HMS Beagle.”“We can tell with fairly good confidence which Sunday in 1848 he wrote this,” Sponsel said. “The two [Owen and Darwin] were working on a publication for the British Navy, a handbook for people on voyages to teach them how to make scientific observations.”Perez added, “The letter, and the entire exchange, gives a perspective on the collaborative process of their work and the kind of instructions that Darwin felt were appropriate for new naturalists on naval expeditions. He makes some interesting comments in the letter, saying that he would have loved to have had this kind of manual on his own Beagle voyage.”“Unknown letters don’t come up very often, maybe about 10 a year,” said Darwin scholar Janet Browne, Aramont Professor of the History of Science and Harvard College Professor. “This letter is unusual in that it is a letter from early in Darwin’s life, before ‘On the Origin of Species’ was written, and with a particular individual with whom he became almost sworn enemies.”It was “On the Origin of Species” that changed Darwin and Owen’s relationship. After its publication, Owen wrote a cruel review of the book, and the relationship disintegrated.The discovery comes as part of Perez and Sponsel’s work for the Darwin Correspondence Project, an endeavor begun in the mid-1970s by American scholar Frederick Burkhardt and now based at the University of Cambridge. Participants there and at Harvard are dedicated to cataloging, editing, and publishing Darwin’s correspondence from throughout his life. To date, Browne said, the project has cataloged about 15,000 letters from “unexpected people in all sorts of categories, including women scientists and African colonial administrators.”“Historians have found principally through this large publishing project that correspondence is a significant element of what scientists used to do,” Browne said. “It turns out that someone like Darwin was writing letters as a way of collecting information. It was part of his scientific method.”The transcription of the letter, which is copyright of the Darwin Correspondence Project, will be published in a forthcoming supplement to the “Correspondence of Charles Darwin” (Cambridge University Press).
More than 2.4 million cancer deaths could be avoided each year in developing countries using prevention and treatment interventions that are affordable and that could be made widely available, according to a new report. And deaths due to children’s cancers are among those that could be curtailed most easily. Costs of treatment for certain common cancers are as little as $100 per course of treatment in developing nations.Even more disturbing, low-cost pain relief medications remain largely inaccessible to patients in developing countries, meaning that most people with cancer worldwide suffer tremendous pain — needlessly — before they die, the report’s authors say.These findings come from the report, “Closing the Cancer Divide: A Blueprint to Expand Access in Low and Middle Income Countries,” being released today by an international group of experts organized by the Global Task Force on Expanded Access to Cancer Care and Control in Developing Countries (GTF.CCC), and hosted by a consortium of organizations that includes Harvard School of Public Health, Harvard Global Equity Initiative, Harvard Medical School, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Partners In Health.Once considered a problem only in wealthy countries, cancer is now a leading cause of death in low- and middle-income countries. About 55 percent of the world’s 12.7 million new cases and 65 percent of the 7.6 million cancer deaths each year occur in these nations.The report was discussed at a daylong symposium Oct. 28 at Harvard Medical School. It was attended by representatives from national governments from low- and middle-income countries, global and national civil society organizations, the private sector, academia, and donors.Lead authors of the report: The report has more than 115 contributors from around the world. The lead authors include Felicia Knaul, director, Harvard Global Equity Initiative, associate professor, Harvard Medical School, Global Task Force on Expanded Access to Cancer Care and Control in Developing Countries, founder, Cáncer de Mama: Tómatelo a Pecho; Julio Frenk, dean of Harvard School of Public Health and GTF.CCC co-chair; Lawrence Shulman, chief medical officer and senior vice president medical affairs, Dana-Farber Cancer Institute, co-chair GTF.CCC; Jonathan Quick, president and chief executive officer, Management Sciences for Health; Rifat Atun, director of strategy, performance and evaluation cluster, The Global Fund to Fight AIDS, Tuberculosis and Malaria; Nancy Keating, associate professor of medicine and health care policy, Department of Health Care Policy, Harvard Medical School; Peter Piot, director, London School of Hygiene and Tropical Medicine; Sir George Alleyne, chancellor of the University of West Indies; Julie Gralow, professor of medical oncology, University of Washington, School of Medicine; Paul Farmer, co-founder, Partners In Health, chair of Department of Global Health and Social Medicine, Kolokotrones University Professor of Global Health and Social Medicine, Harvard Medical School.[youtube https://www.youtube.com/watch?v=9cDFGAUncnI]
The Dudley House Jazz Band and Harvard GSAS are proud to present the music of Horace Tapscott and the Pan Afrikan Peoples Arkestra. The concert will take place on Saturday, December 10 at 8 p.m. in Dudley House on the Harvard campus and is free and open to the public.Born in 1934, pianist and composer Horace Tapscott grew up in the African American community of Los Angeles, performing throughout the city and touring the country in the late 50s. While Tapscott’s prospects for a national career were bright, he returned to L.A. in the early ’60s with the goal of fostering African American music in his hometown. Continuing this mission until his death in 1999, Tapscott founded the Pan African People’s Arkestra in 1961, a group designed to preserve, develop and promote the work of local musicians. Spurred by Tapscott’s powerful compositions, the group pushed the boundaries of the avant garde, and soon became the center of Los Angeles’ creative music scene.Despite Tapscott’s important role in African American music history, his music remains under-recognized outside of Los Angeles. The Dudley House Jazz Band is proud to present a concert of music by Tapscott and members of the Arkestra, including music by saxophonists Jesse Sharps and Fuasi Abdul-Khaliq, two Arkestra alums who have gone on to prominent careers in the U.S. and abroad. The concert will conclude with a new arrangement (by the composer) of Abdul- Khaliq’s Eternal Egypt Suite, an extended composition that has not been performed anywhere since 1976.The Dudley House Jazz Band is an ensemble of graduate students from Harvard’s Graduate School of Arts and Sciences, as well as Harvard undergraduates and community members. The group specializes in performance of historic repertoire, including a 2010 debut of a new arrangement of Mary Lou Williams’ Zodiac Suite. This concert is made possible through the permission of UGMAA Foundation, which continues to advance Horace Tapscott’s musical and community vision. Read Full Story
Read Full Story John W. Hutchinson, Abbott and James Lawrence Professor of Engineering and Gordon McKay Professor of Applied Mechanics Emeritus, has been elected to foreign membership in the Royal Society.He was among eight foreign members and 44 new fellows welcomed on May 3 by the United Kingdom’s elite national academy.Hutchinson is a seminal scholar in the field of solid mechanics and materials engineering, and is more highly cited than any other researcher in this area.Hutchinson studied engineering mechanics as an undergraduate at Lehigh University. After earning his Ph.D. in mechanical engineering at Harvard in 1963, he spent a year in Denmark before returning to join the Harvard faculty, where he very soon made dramatic contributions to the study of buckling in elastic structures.Over a 50-year career at Harvard, he has been one of the major developers of nonlinear fracture mechanics. He has made groundbreaking contributions in micromechanics, including the plasticity of polycrystals, cracking of fiber-reinforced ceramics, and delamination of thermal barrier coatings (TBCs).For example, ceramic TBCs are widely used in aircraft and power generation turbines to shield the engine blades and other metal components from high temperatures. However, the use of TBCs contributes to an industry trend toward engines that operate at even higher temperatures, threatening the durability of the coatings.Concern for plastic deformation at the scale of microns led to his publications in strain-gradient plasticity, which have sparked a world-wide explosion in related research.
Read Full Story Harvard has received Gold level Bicycle Friendly University (BFU) designation making it the highest-ranked BFU in the Ivy League and New England, and one of only 10 gold level BFUs nationwide. The League of American Cyclists, which gives out the awards, noted the University’s deep commitment to biking as well as its employee benefits that encourage biking and significant participation in the Hubway bike-share system.Harvard has long supported the installation of bike infrastructure from bicycle racks to dedicated lanes and routes. The Harvard Sustainability Plan sets out a commitment to increase the bikeability and safety of the streets in and around Harvard’s campus. Harvard’s application for the BFU award was spearheaded by the University’s CommuterChoice program, which provides the Harvard community with a wide-range of sustainable transportation options from discounted MBTA transit passes to programs that encourage walking and biking.“The University is clearly trying to make biking easier,” said Harvard T.H. Chan School of Public Health employee Kelly Blondin. “I bike from Cambridge to Longwood every day and the reimbursements I receive for tune ups and maintenance are great. I’m looking forward to watching Harvard do even more for the bicycling community.”As one tangible example of Harvard’s commitment, the CommuterChoice Program hosted Hubway on Thursday, October 23rd at Harvard’s campus for the launch of the Emerald Explorer bicycle, a one-of-a-kind, limited edition, “unicorn” Hubway bike designed by Harvard employee Amy Fater, winner of the #HubwayEveryday Bicycle Design Contest.
Republicans scored a significant victory on Election Night, winning control of the Senate and extending their majority in the House. The results could be seen as a referendum on GOP policies, but also as a rebuke to President Obama. David King, a senior lecturer in public policy, provided his perspective on the outcome in a Harvard Kennedy School (HKS) interview. HKS: What message did the voters send Tuesday night? Which issues resonated the loudest?KING: I was surprised by the size of the Republican wave on Tuesday; if we think of Congress as a ship, the thing has been rocking wildly side-to-side.President Obama had strong majorities in Congress after the 2008 election. Then voters sent Democrats home in 2010 as the Tea Party wing of the Republican Party swept into Congress. In 2012 the voters repudiated Republicans across the board and returned President Obama to the White House. And now this — voters must have seasickness.I do not think there were substantive issues that resonated loudly. Yes, there was fear in the air — an anxiousness about ISIS and Ebola and the economy — but the bell that rang loudest had an anti-Obama clapper.Maybe we should stop calling these “midterm” elections and talk about short-term elections, because the American voter does not seem to have a long-term sense of where the country should be going or how we should get there.HKS: What do the Republicans hope to accomplish with control of both the House and Senate for the first time since 2006?KING: It will be difficult for either party to enact major changes, because Democrats in the Senate are perfectly capable of stopping bills from passing. Procedurally, it is unlikely that President Obama will be signing many Republican “stand-alone” bills, and he’ll be ready to use his veto pen. So the most likely path forward for Republicans will be to tack “policy” bills onto a handful of must-pass spending bills. This is possible because non-germane pieces of legislation are allowed to be amended onto spending bills in the Senate — but not in the House. If Alabama’s Richard Shelby becomes the next chairman of the Senate Appropriations Committee — and that’s likely — then he will be in an especially strong position to control the fate of legislation.There will be some easy wins. President Obama likes the Trans-Pacific Partnership free-trade agreement. Senate Democrats got in the way last year, and it should be much easier with Republicans in charge of the Senate.HKS: How can and should the president work with Congress in his final two years in office? Is there any common ground on which to compromise on major policy issues?KING: President Obama has shown little capacity to compromise. He did not seem to like the U.S. Congress even when he was a member of it, and he has kept his own party leadership at arm’s length for six years. That is unlikely to change. Instead, President Obama will issue executive orders with abandon and attach signing statements to bills that he does sign. He will almost certainly work to support and defend his signature accomplishment — health care reform — while giving the program more time to work. The economy is getting stronger. Health care reform — as long as it’s not called “Obamacare” — has been much more popular than most people expected, and at this stage the president may want to take care of his legacy.HKS: How do yesterday’s results affect the ground rules for the 2016 election?KING: This election was a harbinger of big money — for both parties — flowing into campaigns. More than $4 billion was spent on the Congressional elections alone, much of it from non-candidate groups, and that will look like chump change two years from now. That would not be a bad thing if the money were spent on strategies to increase turnout across the board, but negative advertising diminishes turnout among moderate voters, alienates young voters, and rallies the core supporters of the parties.HKS: Any other thoughts to offer on the election?KING: We need to remember that political parties and candidates are not in the business of promoting or protecting democracy. They use democratic rules and institutions to get power, certainly, but candidates live in fear of mobilizing the “wrong” voters. Frankly, democracy is too important to be left up to the parties and the candidates. We need to encourage better people to run at all levels of government. We need to do all that we can to balance the power of big money with the power of big ideas.
Read Full Story Contrary to conventional wisdom, growing up with a working mother is unlikely to harm children socially and economically when they become adults, new research by a Harvard Business School professor concludes.The “working mother effect” actually improves future prospects, especially for adult daughters of mothers who worked outside the home before their daughters were 14 years old, according to recent findings based on a comprehensive survey of 50,000 adults aged 18 to 60 in 25 nations worldwide in 2002 and 2012.The research, which provides the basis for two forthcoming academic papers, is one of a number of projects led by faculty affiliated with Harvard Business School’s new Gender Initiative. The Gender Initiative, announced today, seeks to further research, education, and knowledge dissemination on issues related to gender and work. To find out more about the initiative: Harvard Business School Launches Gender Initiative.The working mother study, authored by Harvard Business School Professor Kathleen McGinn, HBS researcher Mayra Ruiz Castro, and Elizabeth Long Lingo of Mt. Holyoke College, found that women with working mothers performed better in the workplace, earning more and possessing more powerful positions than their peers with stay-at-home mothers.
Stories of learning, teaching, and turning points, in the Experience series.In 1986, Harvard “rescued” George Church — in his telling, at least — when the Medical School hired him as an assistant professor in its young Department of Genetics.In the decades since, Church’s efforts to make DNA sequencing faster and cheaper have helped drive a genomic revolution that is transforming science and advancing at a rate that surprises even him.Church, who worked on the groundbreaking international Human Genome Project to decipher humanity’s genetic code, is known for his outspoken style and willingness to engage with the public on ethically and technically challenging subjects, and for bucking the secrecy that typically surrounds human subjects research. His belief that promising privacy is disingenuous and that people deserve to see all their medical and genetic data led him to establish the Personal Genome Project, which integrates genomes with other data and makes that information openly available worldwide.The young Church struggled in the classroom to the extent that he had to repeat ninth grade and his first year of graduate school. Those struggles were offset by his voracious appetite for science, an ability to work independently, and a passion for laboratory work that has sometimes blotted out all else.Q: I saw that you were born on an Air Force base in Florida.A: I had three fathers, as my mother remarried. The first one lasted about eight months post-birth, and he was the Air Force pilot, a pretty colorful character. I knew him off and on through the years, up until his death. He was the sort of father that a young boy would admire, because he wasn’t tied down by actual responsibilities. That was Stew McDonald. He was called Barefoot Stew. He was inducted into the Water Ski Hall of Fame. He wasn’t a terrific athlete — I mean, obviously he was a pretty good one — but his real contribution to the sport, which was relevant to me, was that he was a good communicator. He was the first ABC “Wide World of Sports” color commentator. . . . He was also just generally charismatic: He was a male model, he worked on film, television stuff as well.Q: And he was your birth dad?A: He was my birth dad, but I don’t think he really influenced me that much intellectually. My second father was a lawyer and had the least influence. Third dad was a physician who had two pretty important roles. He sent me away to school, to an awesome high school. Both my stepbrother and I went away at roughly the same time. It might have been just to get the young teenage boys out of the house, but in my case it was very good. It was a liberal East Coast school, Andover, which is where the Bushes went, and [Harvard chemistry professor] George Whitesides, and a bunch of other interesting people. And the other thing he did was just being a physician. I could look at his medical technology and I somehow was enthralled by it.Q: Was his last name Church?A: Yes, that’s where I got the Church.Two big influences shaped my life. I think I was 10 when the New York World’s Fair came along. It was like a very intentional simulation of the future. I was totally taken in by this facade, because they had things like touchscreens, where you could draw a picture of anything, and then almost as soon as you punched “Go,” a weaving device would produce a fabric with a repeating motif that you had sketched. They had jetpacks, and amazing buildings made out of plastic, and the key one for me was they had animatronic robots, like Abraham Lincoln. He would clutch his lapels and I think he would stand up and deliver a speech. I got this illusion as to what science and technology was. I really felt like that’s the way the world should be in 1965.It didn’t take too long for me to become disillusioned. Not only was it not like that in Florida, it probably wasn’t even like that in New York once they shut down the World’s Fair. And it might not ever be like that if I didn’t do something about it. So I sort of felt like, if I want that, I have to work for it.Another thing that was very influential was I lived on the water most of my life. I lived either on the canals in Tampa, on an island, or on the bay in Clearwater. That meant I could kind of wander through the mud and find echinoderms. I found things that looked like starfish, but they were just like two arms. You could squeeze them, they would squirt water. I actually figured out what they were, and I figured out how dragonfly nymphs turned into dragonflies.I was using books — even though I had a lot of trouble reading. By using the index and using photographs, I could figure out just about anything. So that kind of set me on a course of independent study. I was not particularly well adapted socially. I had dyslexia, narcolepsy, OCD, ADD — all these things were very mild, but made me feel different. I was desperate that I would not stand out, which I now think quite common. But at the time — it felt scary.Q: You went to Duke for undergrad?A: One of the downsides of going to Andover was that as a Florida boy I became pretty sick of the cold after four years. So the only colleges I applied to were Stanford and Duke. I went to Duke, where I could place out of everything — math, physics, chemistry, and biology. My freshman year, I was taking all junior, senior, and graduate courses. I just wanted to see what’s the most advanced course I could possibly find in this university, and see can I handle it?My freshman year, I was taking a second-year graduate course in virology, and the professor found out about halfway through the course that I was a freshman. He says, “I don’t know how you got me to sign that thing, but you really shouldn’t be taking this course.” And I said, “Well, if I fail, I fail.” I did fine in the course. But I remember it was a real struggle. I spent more time on that course than my other four courses put together. But I did OK, and that basically told me there was no course I couldn’t take.So I finished two degrees in two years: chemistry and biology. I took a fair amount of math. Most of the math, physics, and computer science I did, I did extracurricularly, because I didn’t want to go at their pace. Biology and chemistry I didn’t mind, because there were labs I wanted to do and so forth.Q: How did you have time in two years to take all these courses? You had your prerequisites waived?A: I worked pretty hard. But science was easy for me, and math, and I just love doing them. Sometimes I could get away with barely going to classes. Other times, like in organic chemistry, I loved it so much I did every single problem set in the back of each chapter. They didn’t even assign any of them. I did them all. It was a full-year course, and I think I had finished the book, including all the problems in it, by halfway through the fall semester. That was pretty typical. But I guess the reason that I did it in two years was I was cheap money-wise. Like a lot of teenagers, I didn’t want to keep being a burden on my parents. Steve Jobs dropped out of college because he was worried about his parents’ finances. I didn’t drop out; I just finished early. I think I also had this feeling that if I took four years to do it, I would probably flunk out, so it would be better to just finish fast. That turned out to be true, that at about the three-and-a-half-year point, I did flunk out, but out of graduate school.‘If you haven’t really filled in the blanks, connected the dots, you’re not really ahead of your time. You’re just dreaming.’Q: At Duke?A: Yeah, I just kind of continued. I started [graduate school] in microbiology, but by that time, I had already spent most of my sophomore year doing crystallography, which turned out to be the best match for me ever, because I’d been searching basically ever since the World’s Fair for a way that I could use computers, math, and biology all together, and ideally physics and chemistry while you’re at it. Crystallography did that.I was interested in crystallography, so I started the process of transferring from one department to the other, which happened, but it had negative consequences. The biochemistry department had no real commitment to me, because I had come in from another department. And I didn’t like the courses, because I’d already taken them. I didn’t keep that to myself. I said, why are you making me take “Enzyme Mechanisms” from Fridovich, because I’ve already got a B+ in that as an undergraduate? They said, well, you know, undergraduate is watered down. I said, no, it’s exactly the same course. They said, well, maybe they gave you an easy grade. I said, OK, I would listen.I took really good notes in the graduate classes [taken as an undergraduate], because I took them seriously. And I looked at my notes and he was verbatim. Same jokes, same everything. So I just stopped going to classes and I flunked two classes. But my research was going well, and to some extent it didn’t fully register that I had flunked out. My crystallography adviser, Sung-Hou Kim, had to pick me up as a technician, which he didn’t complain about. He was a really terrific guy. I’m still good friends with him. He went to bat for me, tried to get them to give me a second chance, and they said no. I had two F’s, so it just was not negotiable.Q: How old were you at this point?A: I think I must have been 20. I wasn’t a teenager, technically, anymore, but I still behaved like one. And I just kept going, assuming that everything was fine. Sung-Hou would tell me from time to time, everything’s not fine. You are not destined to be a technician. You’re designing experiments, and people like me aren’t going to necessarily let you do those experiments. He said, “You really have to apply to graduate school.” So I did. But still being extraordinarily immature, I applied to one graduate school, which was Harvard. I didn’t feel arrogant, but the arrogance of someone who flunked out of Duke applying to one graduate school is crazy. But I got in.I had applied to Harvard two years before and I turned down Harvard to go to Duke, which must have flabbergasted them at the time. It was the same department that I eventually got into. And so, to them, bureaucratically, they were just readmitting somebody that they’d already admitted, who in fact, in those two years, got five papers, some of which as first author. Maybe they didn’t notice the F’s, or they didn’t care about the F’s. Whatever it was, it was one of many times that Harvard has rescued me from myself. That was a pretty dramatic rescue.So I went to Harvard, and I said, OK, this time I’m not going to screw up. I matured overnight. Part of my problem was I was just constantly in this lab mode, where I’d spend 105 hours a week in the lab. I was just like on this treadmill of excitement. So I said, I’m going to take three months off and just read and think and plan. And I’m going to pass all the courses. Fortunately, there was really only one required course, which was taught by a crystallographer, Don Wiley. . . . It was a wonderful course. It was required and most of the people hated it. It had easily 45 hours of homework a week, and most people would leave it until the end of the week, and then they would just have to pull all-nighters and stuff. I would do it the second it was handed out. They’d hand it out, I’d go straight to the library, and I would finish it off.Somewhere in the early fall — I was still worried [about flunking] — I show up for class a little bit late, sit in the back, and on the slides is one of my papers. He’s giving a slide presentation on one of my papers. Don doesn’t know me at this point. He didn’t even make the connection between this paper and me. And I say, you know, I may actually pass this class. Years later I was a teaching fellow for that course.But I knew who I was going to work with. It wasn’t Don Wiley, because I’d already done crystallography. It was Wally Gilbert.Q: So what was it like working in these very high-end labs? Had Gilbert won the Nobel Prize by then?A: He won it after I’d been there three years. And he founded Biogen during that time as well. I was very excited about Biogen. So what was it like being in high-end labs? I took it for granted, quite frankly. I had gone to an elite high school, where I had access to awesome facilities, and I did independent chemistry. I would be in the lab by myself on Saturday morning, playing with dangerous organic chemicals, and it seemed perfectly ordinary to me.By the time I got to Wally’s lab, I considered myself an independent researcher. I did not consider myself a student. Even earlier, at Duke, I got an NSF [National Science Foundation] fellowship. I was not beholden to the head of the lab, or to my parents or anybody else. It was not an entirely rational self-evaluation, but I considered myself an independent scientist who could do whatever I wanted. I considered Wally as a very valuable member of the community, but he was just a bright scientist that I could talk to.And the companies I didn’t consider that special, [though] I think they were very special at the time. Most people considered them either with contempt or they considered them like some amazing thing that you couldn’t possibly dream of doing. Only Wally and Mark Ptashne could do that. And I was just like, oh, yeah, it’s another thing to do. Because even before I learned about Biogen, I had been a consultant for Bio-Rad. I was one of the first Biogen employees, while I was between my thesis and waiting for my girlfriend, who’s now my wife, to finish her thesis. But back then we were just planning on going to the West Coast for postdoc. So I waited for six months and I worked at Biogen.Q: Tell me about your thesis project. It seems to have had a pretty big impact on the industry.A: My thesis had two parts. The first part was working with a project that [French scientist] Bernard Dujon brought with him on a sabbatical. The second half of my thesis was on genomic sequencing, which is really what I had planned on doing when I came to Wally’s lab. During that 1977 summer that I took off thinking about things, I thought of all kinds of inventions having to do with homologous recombination and multiplex sequencing and so forth, which I’m still doing. Oh, and DNA nanostructures. And then I started knocking them off over the years.So the first half: Bernard Dujon came and there were no benches for him, and there’s no acknowledgement that he was there, even though he should have been an esteemed visiting professor. But he was a young professor. So he got a cart, the kind of cart that you’d push bottles around on, and that was his bench and desk. I said, “Hey, you know, you can use my bench.” I didn’t have much space, but I was willing to split it. I got to talking to him, and I got really interested in what he was working on, which ended up being the first intron with genetic function. He had discovered this intron — not knowing it was an intron — before Phil Sharp discovered his introns, for which Phil got a Nobel Prize. But Bernard had the first intron, the first gene-drive, and the first meganuclease, meaning the first way you could get a very specific cut. The meganucleases led eventually to genome editing, now associated with [editing tool] CRISPR. These are resonating with my lab today, but this was back in ’78-ish. Everything just seemed really cool with me. Most of the people around me had no idea what he was talking about. He had a French accent, and he was referring to the papers that were in, like, the fourth annual Brazilian conference on fermentation. That’s where they would publish back then. But I went through this, and I quickly got a couple of papers.So then I had four years without any publications, from 1980 to 1984 — zip — because I was working on this really hard problem, which was genomic sequencing. It wasn’t the first sequencing method by any stretch, but this one was the first instance of “multiplexing,” where you essentially got more information just by re-probing, which is the basis of most of the modern next-generation sequencing. I can’t say that I had conceived of every nuance of next-gen sequencing in that thesis, but there were some pretty significant components.Anyway, it was also the first method by which you could sequence directly from the genome without amplification or cloning, which was very unusual. It predated PCR [polymerase chain reaction], but in a way, it outdid both cloning and PCR in that it could sequence unamplified DNA. I applied that to two pretty hot topics, which had to do with immunoglobulins — immunoglobulin introns — which were new. Turned out they had functions inside them, which were enhancers, and I found evidence for enhancer-binding proteins. So enhancers were brand new. Introns were fairly new. And here we have an assay for function inside of the intron enhancers. That was a good enough thesis that I basically got my professorship at Harvard two years later based on the thesis. I had almost nothing to show for my postdoc. I did six months at Biogen, kind of wrapping up my thesis, and then I did a year and a half in Gail Martin’s lab [at the University of California at San Francisco], which was an amazing lab, but it was pretty far from my thesis.Q: She did more developmental biology?A: Yes, developmental biology. She was one of the few embryonic stem cell researchers in the world. This is in 1984. I figured I would apply genomic sequencing or something like it to developmental biology somehow. So I learned it, but ’85 was way too early for stem cells, and we needed a bunch of new technologies.At this point, the same girlfriend that I waited for, Ting Wu, had gone to Stanford, decided she didn’t like her project, and she went back to the East Coast. So I tried my best to get back to the East Coast. My friend from graduate school, Gary Ruvkun, was just starting as a professor in the [Harvard] Genetics Department, which was a new department. They had an actual tenure track, which meant that everybody had a chance at tenure, at least. So I applied.A Harvard talk that I gave was mostly based on my thesis, [but] I did mention at the very end that I wanted to sequence the E. coli genome. This was a new concept, the idea of sequencing a whole genome. This was 1986. The first genome was still eight years away, so this was fairly visionary. I had a new technology as well, so it wasn’t just, oh, I’m going to do something ridiculous. I showed them one slide of actual data from my new technology. The room was packed, not because of the sequencing, but because the title was “Functions of Introns in Immune Genes” — or something like that. Immunoglobulin introns and enhancers were very popular. I’d only been away for a year and a half, and so I had a lot of friends in town. It was kind of artificially packed.And I think they may have just looked at the audience size, or the promise of the [Human] Genome Project, or whatever. The Genome Project was just hitting — we had just had two or three meetings. I was the one person that went to all of the first three meetings. So I was an insider on this project, which may or not go anywhere. So I think that’s how I got in. It was the second of three big things that Harvard did for me where I really didn’t feel deserving. I shouldn’t have gotten into graduate school. I shouldn’t have gotten a professor position. But I did. [The third big thing: tenure.]Q: You didn’t look back, right?A: I did not, and I got an HHMI [Howard Hughes Medical Institute grant] straight out of the box, which was very rare at that point for assistant professor. I got a DOE [U.S. Department of Energy] grant about the same time. That was my first grant, and it was the first Genome Project grant.Q: So this was ’87 by now?A: About ’87, yeah. I was having a great time, because between the HHMI and the DOE funding, I didn’t have to write any more grants for a while. Plus, I had my startup money from Harvard. But there was some baggage and some problems that came along with the Genome Project. Wally Gilbert and Sydney Brenner were leaders in the field, and they basically said, what we need are warehouses full of technicians. Wally called them “mindless technicians with Walkmen,” and Sydney called them “a penal colony” to work off any infractions you had made in scientific misconduct. I’m trying to recruit graduate students to do this in a creative way while these two leaders of the field are making it sound like a terrible job. And then the entire Microbiology Department here at Harvard Medical School — it’s very rare you get a department to agree on anything, but they could agree that the Genome Project was a bad idea — and they wrote in to Science or Nature. And I’m thinking, what a terrible way to start as an assistant professor.Q: The project aimed to sequence the human genome for the first time. What did they think was bad about it?A: The project was poorly framed, but I didn’t have much say in it. My framing was this should be technology development where we bring down the cost and we apply it to microorganisms first. But the framing of the old guard was we should use existing technology, scale it up in an industrial way — like Toyota or something — and spend $3 billion for three billion bases, a number they kind of pulled out of the air. The costs at the time were probably higher than that, but it was a reasonable goal. It was an inconceivable amount of money at the time. Typical grants were $100,000. And skeptics were thinking of this as $3 billion going into one professor or a small team. That was critique one.Critique number two was that it was junk DNA, it was 99 percent junk, and why should we spend 99 percent of $3 billion on something we didn’t care about? Why couldn’t we be more selective? And even the 1 percent was going to be uninterpretable. The interpretation was going to come from the $100,000 grants, not from the $3 billion grant.The third critique was that once you started something of that size, you could never stop it. It was like a juggernaut.All of these were fair critiques, and I actually kind of sympathized with them, even though I was gung-ho on the technology side. I was disappointed that there was so little technology and that it was far too expensive. Three billion dollars was an unsustainable number. We might get to the end of the first one [genome], but we would never do a second one, and that, to me, was very disappointing. I also felt that there was too much emphasis on the human genome, rather than comparative genomics, which was an uncoined term at the time. I felt like the interpretation problem could be largely handled if you compare sick vs. well, E. coli vs. salmonella, worm vs. fly. There were a bunch of comparisons you could do that would immediately add value. Eventually the field caught up to some of those concepts and quickly brought some leaders into the fold that had been critics.Q: Clearly, there have been many developments over the years since. What would you say are the biggest successes? And are there particular failures, stumbles along the way, that you may have learned something from?A: My experience with crystallography [at Duke] was successful. We still use the coordinates of transfer RNA in many people’s research. The concepts from my thesis of multiplexing and barcoding were good. Some of the ideas I had about DNA nanostructures I didn’t publish, and so I think they were a failure in a communication sense, but my lab and other labs are back to making that a success.Some of the failures were just timing things. Nanopores and DNA nanostructures were things that I came up with — in ’88 for the nanopore sequencing, and the nanostructures was ’77 — and they’re just now coming into real-world uses in 2016. So I consider that a kind of failure. Some people say, oh, wow, you’re ahead of your time. But I think that if you haven’t really filled in the blanks, connected the dots, you’re not really ahead of your time. You’re just dreaming.Q: How many companies have you started?A: The narrowest definition of “start” means you’re formally listed as a founder. So I’ve founded about one company per year since 2005. This year, if all goes well, I will be involved in founding nine companies simultaneously. It’s not only unusual in the number, but it’s unusual in the type. The ones from 2005 to the present were mostly some other professor or some venture capitalist working with me on a new idea, and then we hire businesspeople and scientists to do it. It’s really pretty low-maintenance. But when nine of your postdocs each want to start a company, and you have to mentor them — of course, I was mentoring them anyway as postdocs, so it’s not that much harder than what I would normally do, just a slightly different set of conversations. But it is unusual, and it’s an experiment. I don’t know how it will turn out. I don’t plan on doing that again.Q: Why do you feel it’s important?A: Here’s an argument about why such startup companies are important. If you’re going to make a discovery, you can publish it in a journal, and hopefully it gets discussed in review articles, and that’s it, you’re done. But if you’re making a technology, you can write primary articles and review articles until you’re blue in the face, and nobody’s going to do it. It’s not sufficient to just write out a patent and lob it over the fence. You have to accompany it. It doesn’t take that much time to do that, but it’s not zero. Probably 10 percent of my time is spent making sure that the technologies that I work on get a fair shake in the marketplace.Q: Another important part of your public persona is as an advocate for genomics, genetic engineering, synthetic biology.A: I’d like to think of it more as a communicator than an advocate. It’s an important distinction, because I think there’s a caricature of scientists as advocates and cheerleaders where they might even be blind to where it’s going. I think my lab and I have authored a lot of papers of a cautionary and bioethical nature, but not just of the hopeless, hand-wringing variety. It’s more like, here’s a problem, potential solution, potential problem created by the solution, potential solution to the problem created by the solution. It’s important to talk about things before they exist, because sometimes these things sneak up on you ridiculously quickly. For example, next-gen sequencing was supposed to take six decades by Moore’s law, which is a pretty aggressively optimistic law. Sequencing didn’t take six decades; it was more like six years.CRISPR came out of nowhere. It’s hard to believe that it’s only three years old, considering all that it’s done. My experience is that things happen much faster than you would expect. It’s not about cost overruns and multiyear delays. It’s more about, oh my gosh, it’s 60 years early.Q: When did you first think that you really should start thinking about bioethics?A: There’s a big feeling you shouldn’t talk about things that you’re not expert on, and you define your expertise very narrowly. One of my colleagues about my age said that over the years, his specialty got narrower and narrower until he was the world’s expert on something he no longer cared about.One of the first things to go out the window is anything having to do with humanities and philosophy and ethics, because that just seems too flaky and fluffy. But I never felt dismissive. The first time I really felt responsible — when would that be? In the beginning of the Genome Project, we had this thing called ELSI: ethical, legal, social implications. Genome Project started around 1990, and it must have been around then.Around 1999 I felt that there was some possibility we’d be sequencing human genomes with next-gen sequencing — plural, not just singular. And I said, we’re going to be doing this. I need to get IRB [Institutional Review Board] approval to do human subjects research. I had no clue as to what that was, but I just knew I needed to do it. So I applied for it, and as I’m doing it, I’m realizing, this is really wacky. They’re promising anonymity and sharing at the same time. How do they know that the data’s not going to escape and get re-identified? It seemed like both were provably going to happen. And what if you discover something that could save a patient’s life? [Because of anonymity] you can’t tell them. So I said, these are three things that are really messed up.The fourth thing was that the consent forms were written by lawyers for lawyers to protect the institution, not to protect the person, which is what everybody said that they were for. So these four things were messed up, so we came up with Personal Genome Project.Q: The Personal Genome Project’s data is open access, with subjects having no promises of anonymity. You said that’s a more honest way to approach this kind of research. But is that also important from a scientific standpoint?A: We wanted something somewhat inspired by open software and Wikipedia. We wanted something where you could share human biological information, where if you wanted to make software that would handle a real human being — in a way that a physician might appreciate, which might include everything about them, their anatomy, their physiology, what they eat, and so forth — you could do that. You would need a big dataset about a person that’s all interconnected, rather than shredding it into pieces [to make it anonymous] and losing information.Some of the proposals were to actually inject bits of false information so that people would be uncertain as to how to identify somebody. But you would also be uncertain about the science. And they said, well, the statistics can overcome the uncertainty on a population. And I just said, you know, we have enough trouble even when we have good data.Fast-forward to today. I would say that many of my lab’s projects, like the Personal Genome Project and like our open-source DNA sequencer and now the $1,000 genome — the goal is not necessarily to dominate the universe. It’s to set an example. I told my lab, “You can really change the world in a very positive way if you don’t care who gets the credit and the money.”Same thing with Personal Genome Project. I think it now is the norm to return information to individuals. It’s the norm to be able to share things in a way where you don’t have to strike up a special deal. Some of them are more open than others, but the point is it’s now the norm to share, and it’s the exception where you coerce investigators to include you as a coauthor just because you’re using their data.Q: You mentioned that you’re working to bring down the cost of genome editing and gene therapy. Is gene therapy, to your mind — with direct applications to human health — the most important thing going forward?A: I’m not sure gene therapy is, but the applications to human health, definitely. And I’m certainly not convinced that CRISPR is the only way to achieve gene therapies. In fact, 2,000 gene therapies are in clinical trials, and a tiny minority are any kind of gene editing, and none of them are CRISPR. That’s obviously going to change. One of the companies I helped start, Editas, will be doing this within a year. I think that things that affect human health are the gene drives which can affect malaria, which has been recalcitrant to vaccines and drugs, and things like Lyme disease — the same story.Q: And with gene drives we’re addressing the vector, not humans directly.A: We’re addressing the vector. We can spread a bit of selfish DNA through the sexual reproductive cycle in rapidly reproducing organisms like the white-footed mouse — vector for Lyme disease —and the Anopheles gambiae mosquito — vector for African malaria — and maybe mosquitoes for Zika virus if that doesn’t have other solutions. Those are big public health issues, and dengue virus and a lot of nematode diseases and so forth. Time and again, you’re seeing resistance to pesticides, herbicides, and antibiotics.Gene drives provide an alternative to that. The mosquitoes do all the work for you, and you just have to drop it from airplanes. Again, you have to do safety testing and get multigovernment approval, but it’s much easier to do that than to have medical foot soldiers who go to remote villages trying to find every last person to vaccinate them.Q: Are you concerned about unintended consequences? Species have been introduced with the best of intentions and turned out to be invasive.A: Many of the things that my lab does, we accompany with a warning of some sort and research on how to make it safer. There’s safety engineering in almost every field of engineering and we’ve tried to champion that in molecular and biological engineering. Sometimes, when we talk about it in advance people say, oh, this is science fiction. But in 2014, we said [of gene drives], look, this time it’s going to really work. Here are some things to consider — ways to make it safe so it can’t escape from the lab, ways that once you do deploy it, if you want to alter it, you can do a reversal drive or an alteration drive. And by 2016 it does work already in four species. You need to talk about it in advance so people can see the problems with the fixes, the problems with the fixes to the fixes, and so forth. We proposed that we and others would develop reversal drives and test those in a physically-contained laboratory environment to see if they worked, and they did. And we also came up with safety mechanisms that would keep it in the lab.We were trying to focus on defense, because we felt it was going to be too easy. For $50, [someone] could do a CRISPR gene drive and eliminate whatever organism they don’t like. Since there are probably 7 million species and 7 billion people, probably everybody has several organisms they don’t like, and you could end up with nothing, which would be a tragedy. So there should be some way of having the discussion, and if somebody goes rogue and does it, a way of handling that.Q: What advice would you have, reflecting on your own career, to a student who looks at what you do and thinks: that would be really cool.A: The problem with getting advice from people who have managed to dodge all the bullets is they don’t necessarily know how they did it.All the failures I’ve overcome? That’s much more important than any successes. I had to repeat ninth grade. I had to repeat the beginning of graduate school. I lost my major source of funding just before I came up for tenure. One of the major things — news flash — that they judge you on for tenure is whether you can support yourself. In each case, it helps if you can think out of the box and think of a new way of doing things. The other thing is: Follow your dreams, even if it does mean taking a risk. If you’re not failing, you’re probably not trying as hard as you could be. And being petrified of failure means you’re going to be probably a very extreme underachiever.One of the things we recruit people for in my lab is being nice. That’s the ethos we try to encourage. “Nice guys finish last” — isn’t that a terrible message to be sending to the next generation?I think what goes around comes around. You have to really want all the teams to succeed, all the boats to float. You want your competitors to not fail. It’s hard enough to get progress in the world if everybody’s succeeding.Interview was edited for clarity and length.
Focus on nicotine overshadowed other hazards attached to smoking device Two chemicals widely used to flavor electronic cigarettes may impair the function of cilia in the human airway, according to a new study led by the Harvard T.H. Chan School of Public Health.Cilia are antennae-like protuberances that are present on 50 percent to 75 percent of the cells that line human airways. They play a key role in keeping the human airway clear of mucus and dirt and allow people to breathe easily and without irritation. Impaired cilia function has been linked to lung diseases such as chronic obstructive pulmonary disease (COPD) and asthma.“Although chemicals used to flavor e-cigs are frequently used, little has been known about the mechanism of how they impact health. Our new study suggests that these chemicals may be harming cilia — the first line of defense in the lungs — by altering gene expression related to cilia production and function,” said Quan Lu, associate professor of environmental genetics and pathophysiology. Lu and Joseph Allen, assistant professor of exposure assessment science, are co-senior authors of the study.The study was published today in Scientific Reports. It is the first to look at the impact of flavoring chemicals in human epithelial cells, which are the cells that line the lungs.Millions of people use e-cigarettes, and a recent rise in use among school-age children has alarmed public health experts. In mid-December, U.S. Surgeon General Jerome Adams labeled youth e-cigarette use an epidemic. Scientific studies examining the potential health effects of e-cigarettes and their myriad chemical components have not kept pace with the rise in use. “E-cigarette users are heating and inhaling flavoring chemicals that were never tested for inhalation safety.” — Joseph Allen, Harvard Chan School Teen vaping rising fast, research says Trend concerns Harvard analyst, though practice is preferable to smoking tobacco Study supports need for randomized clinical trials to clarify the role of e-cigarettes in smoking cessation In addition to being used in e-cigarettes, diacetyl is used as a flavoring agent in foods such as butter-flavored microwave popcorn, baked goods, and candy; it can create a variety of flavors. Diacetyl is considered a safe ingredient in foods, but evidence suggests that it can be dangerous when inhaled. It has been previously linked with bronchiolitis obliterans, a debilitating disease that was dubbed “popcorn lung” because it first appeared in workers who inhaled artificial butter flavor in microwave popcorn processing facilities. After the link between diacetyl and popcorn lung was reported, 2,3-pentanedione was sometimes used as a substitute.In the new study, researchers used novel lab techniques that allowed them to examine the impact of both diacetyl and 2,3-pentanedione on epithelial cells in a system that closely mimicked the human airway epithelium in vivo. They exposed normal human bronchial epithelial cells to the chemicals for 24 hours. They found that both diacetyl and 2,3-pentanedione were linked to changes in gene expression that could impair both the production and function of cilia.In addition, the researchers found that even low levels of both chemicals affected gene expression, suggesting that current standards for safe limits of exposure to these chemicals for workers may not be sufficient. There are no such standards for e-cigarette users, according to the authors.Other Harvard Chan authors of the study included lead author Hae-Ryung Park, Michael O’Sullivan, Jose Vallarino, Jin-Ah Park, and David Christiani.Funding for the study came from a National Institutes of Health (NIH)/National Institute of Environmental Health Science (NIEHS) R01 grant ES022230 and a Harvard NIEHS Center grant (P30ES000002). E-cigarettes’ usefulness for quitting smoking uncertain In a previous study, Allen and Harvard Chan colleagues found flavoring chemicals — primarily diacetyl and 2,3-pentanedione — in more than 90 percent of e-cigarettes they tested.“E-cigarette users are heating and inhaling flavoring chemicals that were never tested for inhalation safety,” said Allen. “Although some e-cig manufacturers are stating that they do not use diacetyl or 2,3-pentandione, it begs an important question — what chemicals, then, are they using for flavoring? Further, workers receive warnings about the dangers of inhaling flavoring chemicals. Why aren’t e-cig users receiving the same warnings?” Chemical flavorings found in e-cigarettes linked to respiratory disease Related