• Transcript
  • Show Notes

On this week’s episode of Stay Tuned, “Playing God,” host Preet Bharara answers your questions about loyalty, congressional hearing practices, and naturalization ceremonies.

Eric Lander is the President and co-founder of the Broad Institute of MIT and Harvard, a biomedical and genomic research lab that’s played a central role in the development of CRISPR, and the leader of the Human Genome Project.

Sign up to receive the CAFE Brief, a weekly newsletter featuring analysis of politically charged legal news, and updates from Preet.

As always, tweet your questions to @PreetBharara with hashtag #askpreet, email us at [email protected], or call 669-247-7338 to leave a voicemail.

REFERENCES & SUPPLEMENTAL MATERIALS

THE INTERVIEW

  • The Broad Institute of MIT and Harvard, Official Site
  • Eric Lander and Robert Weinberg, “Journey to the Center of Biology,” Science, 2000
  • Eric Lander, “The Heroes of CRISPR,” Cell, 2016
  • “Engineering the Genetic Toolbox,” Broad Institute
  • Description of Phenylketonuria, National Institute of Health
  • Buck Rogers in the 25th Century (dir. Harlan Tarbell), UCLA Film Archives/Ron Hall, 1934
  • Eric Lander, 2018 William Allen Award Acceptance Speech on Common Disease, American Journal of Human Genetics, 3/3/19
  • Julia Belluz, “After China’s Gene-Edited Baby Debacle, CRISPR Scientists Want a Moratorium,” Vox, 3/13/2019
  • Eric Lander, Francoise Baylis, Feng Zhang, Emmanuelle Charpentier, Paul Berg et al, “Adopt a Moratorium on Heritable Gene Editing,” Nature, 3/13/2019
  • Julia King, “DNA Forensic Testing Industry Faces Challenge to Credibility,” The Scientist, November 1989
  • Eric Lander, Testimony on Forensic Science before the United States Senate Committee on Commerce, Science, and Space, Broad Institute, 3/28/2012
  • Eric Lander, “Fix the Flaws in Forensic Science,” New York Times, 4/21/2015
  • Eric Lander et al, “PCAST Releases Report on Forensic Science in Criminal Courts,” gov, 9/20/2016
  • “A Review of the FBI’s Handling of the Brandon Mayfield Case,” S. Department of Justice, Office of the Inspector General, 2006.
  • “Eric Lander, Geneticist and Mathematician, Class of 1987,” MacArthur Foundation
  • Gina Kolata, “Broad Institute Director Finds Power in Numbers,” New York Times, 1/2/2012

Preet Bharara:              From CAFE, welcome to Stay Tuned. I’m Preet Bharara.

Eric Lander:                  Anything that comes into court wearing the mantle, the robe, of science, claiming all of the trappings of science, ought to have to live up to the standards of science.

Preet Bharara:              That’s Eric Lander. He’s the president and co-founder of MIT and Harvard’s Broad Institute. It’s a biomedical research lab that has played a central role in the development of CRISPR, a gene-editing technology with profound implications for the future of disease and human development. A seminal figure in the mapping of the human genome, Lander has been a laboratory researcher, Harvard and MIT professor, and thought leader in the growing field of genetics for more than three decades. Lately, he’s been focusing on creating global rules for gene editing, helping to jumpstart innovative research companies and finding more reliable ways to use DNA forensics as evidence in criminal trials. We’ll get into all of that, plus the history of the Human Genome Project, the risks and rewards of scientific progress, and the role of the United States in the global quest to eradicate disease. That’s coming up. Stay tuned.

Preet Bharara:              Hey folks. Now it’s time to get to your questions. I’m traveling with my family in Israel this week, so I didn’t expect to be fully plugged into minute-by-minute news, so I took this opportunity to answer some questions that are not based on the ever-changing news cycle. Next week promises to be a big week, and we’ll be back with a lot more analysis.

Preet Bharara:              This question comes in an email from Josh.

Preet Bharara:              Hi. Non-news cycle question for you. Trump prizes loyalty. I recall that W did too. I found it alarming then too. But on reflection I’m not sure I can put my finger on exactly why an emphasis on loyalty should be disconcerting, and I’ve never been in a powerful executive role. Maybe the stresses and demands of that role make loyal aides imperative. I’d love to hear you reflect on whether, and why, we should care about loyalty seekers.

Preet Bharara:              Well, Josh. That’s a great question, and I think it turns on what you think loyalty means. Loyalty, as I understand it, is a wonderful thing, is a fine thing. I’ve been in executive roles and I’ve been in supporting roles. In the ordinary sense, I think executives and co-workers, even who are peers, deserve and expect a certain degree of loyalty from their colleagues. By that, I think you mean having your back, defending you, not throwing you under the bus, being aboveboard and honest with you, and being generally supportive. If you need a helping hand, you’re there to support your colleague. That’s what I understand to be loyalty in the workplace. Loyalty in friendship is incredibly important. You protect your friends, you protect your family. I think loyalty is an incredibly important quality. I think you can judge people on whether they’re loyal or disloyal. Whether they desert their friends in times of need, or they trample their friends in times of ambition. That tells you a lot about a person, and it turns on whether they are, the way most people understand it, loyal or not loyal.

Preet Bharara:              On the other hand, there are limits to loyalty. The way in which Donald Trump sometimes seems to mean loyalty I think is deeply problematic and borderline criminal, if not actually criminal. When the president of the United States wants people to be loyal to him, above their loyalty to the Constitution or the law or to ethical obligations, well, then that’s not good loyalty and it should be disconcerting. It should be called out and it should not be excused. When the president of the United States, early in his tenure, pulls in Jim Comey the FBI Director and talks about loyalty in the way he talked about loyalty was disconcerting to the FBI Director and should be to every American. Because it seems that what he was talking about, and what he seems often to be talking about, is people putting personal loyalty to the president of the United States. Meaning, defending him at all costs no matter what he has done, to put that kind of loyalty over obligations to the rule of law and the public. That’s a terrible thing and should not be countenanced.

Preet Bharara:              This question comes in an email from Robert.

Preet Bharara:              Dear Preet:

Preet Bharara:              I’d say this question belongs under the rubric of congressional trivia, but I don’t think it’s trivial. When did it become common to prop up huge posters during Congressional hearings? They are obviously made for the audience and the television camera, props that amount to propaganda for the side that resorts to these antics, and that side seems to be exclusively the Republicans. The posters stare the audience in the face in the hearing rooms and on TV. They contribute nothing of substance to the hearings themselves. Why isn’t this practice banned? I look forward to hearing your comments.

Preet Bharara:              I don’t mean to belittle your question because it’s a good one. I’m laughing only because I was a Congressional staffer for four-and-a-half years. Even though maybe in recent times you’ve been seeing the posters used by Republicans, Democrats use them also. They’re not only used in the House, they’re also used in the Senate. Although I typically did not see them used very often at hearings. Where I did see poster boards used, was on the Senate floor. You have a member of the Senate standing at his or her desk giving a speech about some topic or about some nominee or about some bill, and there would be some poster board next to the senator that either had a chart, if you’re talking about the economy, or you might have a poll quote from a nominee that you were voting against, or some other such thing.

Preet Bharara:              When I talk about this I get a little PTSD because my job as Chief Counsel to Senator Schumer when he was addressing something relating to my portfolio, whether judges or criminal law or something else along those lines, and he wanted to have a poster board, it was my job to get the poster board done, make sure it was done on time, rush to the floor of the Senate. The senator would stand and I had to procure the easel, and I had to make sure it was positioned properly, in my little staff chair sitting next to the Senator. If you watch CSPAN ever, you’ll see that there’s always a staffer standing next to the senator, and on occasions where there was a poster board of the type he described, I was always incredibly nervous that I might knock it over and have an embarrassing moment on CSPAN.

Preet Bharara:              I do remember, in connection with hearings now that I think about it, during Supreme Court confirmation hearings occasionally senators would us poster boards too so the public could see some line from a decision that was rendered by the nominee, whether it was future Justice Roberts or future Justice Alito, and I remember there being even more nervous because you didn’t have an easel and you would have to stand behind the member, like I did on occasion, and hold up the poster board and make sure you weren’t nervous and shaky. Invariably, during those hearings, when I would hold up one of these posters, whether you thought they were silly or not, I would get snarky emails and texts from friends of mine saying, “Hey, great job holding up that poster.” That’s why I got paid the big bucks.

Preet Bharara:              So, yeah. I hear your point. Sometimes the posters are silly, sometimes they’re self-defeating. I don’t know when they began. They can sometimes be effective to reinforce a point. Both sides do it, both chambers do it. I did note, a few weeks ago, as others did, the quite silly poster that some of the Republicans put up in connection with the impeachment inquiry, and that was the one where Republican House members put up a poster with the number zero, a big number zero on it, to denote, according to the poster, the number of days since Adam Schiff followed the rules. I guess, trying to make the point that he wasn’t following the rules. But the literal meaning of their poster, zero days since he followed the rules, means that the day before he was following the rules.

Preet Bharara:              The poster boards, they’re a feature of modern life, I think, as we have to suffer through them.

Preet Bharara:              This question comes from Twitter user [Abra Barons 00:07:24].

Preet Bharara:              Hi, Preet Bharara:

Preet Bharara:              My sister was just appointed as a federal judge and will be presiding over her first naturalization ceremony soon. Any words of advice? Asking for her because she doesn’t have Twitter. Thanks, and love your work. #askpreet.

Preet Bharara:              Well, first of all, congratulations to your sister. It is a high honor. Not only do you get to be someone who delivers justice on a daily basis and the public count on judges to deliver justice on a daily basis. There’s also that side benefit of light tender. I don’t know if you’re asking words of advice about the naturalization ceremony or about being a judge, but let me just comment on both.

Preet Bharara:              With respect to the naturalization ceremony if it hasn’t already passed, she should speak from the heart. On the outside of my official duties as US attorney, the most moving thing I ever got to do was preside over a naturalization ceremony of scores of people who were swearing an oath of allegiance to the United States of America. In particular, it was moving for me because I’m an immigrant, as you know, and was naturalized at the age of 12 when my parents became citizens of the United States. I, in fact, brought my kids, took my kids out of school so they could come see the naturalization ceremony. I brought my parents. In fact, at the end of the ceremony when all these scores of people had been inducted as new citizens of the United States of America, my mom and dad came up to the front and we all together led the new citizens in the Pledge of Allegiance. So, she should enjoy that ceremony, take it in, and realize how marvelous a country this is. She should, I hope, be an advocate personally and professionally for the country being open and welcoming to immigrants like me.

Preet Bharara:              Second, any words of advice on being a judge. Far be it from me to provide any advice, but I did a little bit in a chapter called Judges in my book Doing Justice. There’s lots of different things that are difficult in the life of a judge and the work of a judge. We ask them, as I say in my chapter, we ask them to be perfect, we ask them to be real, we ask them to be meticulous, we ask them to be infallible. We ask a lot of judges, and they’re just people, and they’re just human beings.

Preet Bharara:              But, from time to time, and I realize that people know that I use time to time a lot as a phrase. But, from time to time, there were people in my office who sought to become judges and became judges. When I was in the Senate I helped shepherd nominees like your sister through the process and they became judges. But after I had been US Attorney for a while, and from the perspective of being the head of the office, I would see some judges not treat lawyers in their courtroom very well. Any time a friend of mine is on the verge of becoming a judge, I actually give them a little speech. I hope it is not patronizing to them, but I mean it with sincerity.

Preet Bharara:              And that is “You have a lot of power as a judge. You wear a robe, and everyone respects you. You can forget over time that the lawyers appearing before you are just people, Whether they’re prosecutors or they’re the defense lawyers. Your words carry a lot of weight, and not just your words but also your expressions and your sarcasm and your disdain. It not only can affect the resolution of a case or the direction of the case because jurors see that, But even the proceedings that don’t have jurors. It can affect the confidence and the self-worth of the people you are directing your ire towards.” I tell people when they’re about to become a judge, I used a phrase I will not repeat on air because it involves an expletive, but I would simply say, “Don’t be a _____.”

Preet Bharara:              And I’ll say, for the purposes of this, I would say, “Don’t be a jerk. There will come a time, you’ll be tired and you’ll be sitting on the bench and some assistant US attorney who’s new to the job will say something that you don’t agree with or you think is not a good argument. You’ll snap at that person and you won’t think it’s a big deal, but to that assistant who is trying to make his or her way as a young lawyer practicing at the highest level, it can be very debilitating. I’ve seen it happen, and there’s no need for it. You’re the judge, you’re the presiding officer in the courtroom. The marshals report to you. Everyone in the courtroom stands when you walk in, they stand when you walk out. And by the way, that admonition to judges to remember that the people in front of them are people, and there’s no need to mock them or debilitate them just because you can, also applies to other people who appear before you, including criminal defendants.”

Preet Bharara:              I recite a story in my book that hopefully has had some resonance with judges who hadn’t thought of this issue before. But in my experience, typically judges in the Southern District of New York, address the parties at the beginning of a proceeding. I don’t think they mean anything by this, and I don’t think it occurred to me until well into my tenure at the US Attorney’s office, but the judges might say, “Good morning, Miss Prosecutor. Good morning, Miss Defense Lawyer, and I note the presence of the defendant.” There’s human being’s greeting offered to the defense lawyer, to the prosecutor, and then this odd notation of the presence of the defendant. Which is odd when you think about it because the only reason anyone is there is because the liberty of the defendant is potentially at stake.

Preet Bharara:              The reason I thought about it was there are some judges, including the former Chief Judge, Preska, who I’ve talked to about this, who had a slightly different ritual that seems to make more sense. She would say, “Good morning, Miss Prosecutor. Good morning, Mr. Defense Lawyer, and good morning Mr. Jones,” or whatever the name of the defendant was. It’s a small civility, and it might not seem like a big thing, but in the absence of that you wonder what a defendant might be thinking about the impersonal nature of the justice system to which he is being subjected, and which may wreak a jail sentence upon him when the judge who is presiding in the case can’t even engage in the simple nicety of addressing him by name and saying, “Good morning,” or, “Good afternoon.”

Preet Bharara:              I think judges need to remember, which mostly they do, but you can forget because judges are human beings and human beings can be forgetful, that everyone’s a person, everyone is trying hard, and people tend to be nervous in court, so just be respectful of that.

Preet Bharara:              Good luck to her.

Preet Bharara:              Stay tuned, there’s more coming up right after this.

Preet Bharara:              My guest this week is Eric Lander. He’s a geneticist who has been at the forefront of the Human Genome Project, the development of the CRISPR gene editing technology, and other biomedical breakthroughs that will reshape our relationship to disease and heredity in the coming decades. He joins me to talk about his work at MIT and Harvard’s Broad Institute, his attempts to regulate genetic experimentation on human subjects, and how a 1989 murder trial has formed the role of forensic evidence. We also talk through the ethics and legality of using gene editing systems, and the difference between genetic correction and genetic enhancement. That’s coming up, stay tuned.

Preet Bharara:              Dr. Eric Lander. Thanks so much for being on the show.

Eric Lander:                  A pleasure.

Preet Bharara:              One reason I’m excited to talk to you, and there are many reasons, because we’re going to talk about science. But one reason is that we’re not going to talk about impeachment, and it’s nice. We are recording this, I should note for listeners, the day after the president was impeached. We’re heading into the holidays, and there’s lots of things that we should discuss that are not related to the president of the United States, but that are also very important for the country and for the world, and for ethics and for science and for disease. I’m really thrilled that you were able to join us.

Eric Lander:                  Well, I’m delighted you’re interested in the topics.

Preet Bharara:              Let’s do some basic stuff first and build some blocks, and then we’ll talk about complicated things like, or at least complicated to people like me who flunked out of science, things like gene editing and the eradication of disease caused by genetic bases. Among other things, you are many things, you are the president of the Broad Institute at Harvard and MIT. Explain what that place does.

Eric Lander:                  Well, the Broad Institute’s best understand by understanding its history. During the 1990s, a bunch of us in Boston were working on the Human Genome Project. We had what turned out to be the leading center for this international project to read out all the letters of the human DNA. During that decade lots of young people began coming together, recognizing that reading out the genetic information was just the start and that the real show was going to be figuring out how it underlies disease and how we can use that information to improve treatment and care for patients.

Eric Lander:                  Around the time the Genome Project was ending, we had the simple idea of, “Could we pull together Harvard and MIT and the five leading Harvard-associated hospitals, in a collaboration to take this next step of building genomic medicine?” And the Broad Institute was the result. It brings together now, oh, more than 4500 people in Boston who are interested in building the tools, collecting the information, making it available, and taking on diseases ranging from diabetes and schizophrenia, to cancer and infectious diseases, all with this common theme that if we understand genetics we get a leg up on the causes of disease.

Preet Bharara:              More basic questions. What is a genome?

Eric Lander:                  Well, a genome is all the information you got from your mom and all the information you got from your dad. Turns out, genetic information is written in this four-letter code: As, Ts, Cs, and Gs. And from each parent you got three billion letters of information. That information encodes the instructions from making about 20,000 proteins that make up your body. Everything from the hemoglobin in your blood to the carotene in your skin, and it also encodes the instructions for when to turn those genes on and off, in what cells during development, what genes should be on and what kinds of neurons and what kind of blood cells in your immune system. Basically, it’s the hard drive of information and the instructions for when to read it out. It’s blows my mind that a mere three billion letters of information, that fits on a little memory stick, is all the genetic information needed to specify the body plan of a human being.

Preet Bharara:              Initially, when the plan was undertaken to sequence the genome, map the genome, were practical applications of that understand at the time or was it just in the interests of discovery?

Eric Lander:                  Well, in fact, the Genome Project was motivated by the idea of finding the genes for very rare genetic diseases. In the early 1980s some ideas were developed that said, “If we knew enough about human genetic information, we could trace the inheritance of different parts of the genome, different parts of chromosomes within the genome, and be able to pin down where were the genes for Huntington’s disease or cystic fibrosis.” At the time it was known there were thousands and thousands of these very rare genetic diseases that most people never heard of, and there was a method that people conceived that would let us find those disease genes. I think the Genome Project was motivated by that medical application. What turned out to be very surprising, is that there were hundreds of more applications that came from that fundamental knowledge. So, as often happens, there’s a very practical medical application that sends the scientific community off to collect very fundamental scientific information, which then turns out to have practical applications.

Eric Lander:                  And it’s this virtuous cycle between fundamental basic science and highly applied medical science, where each drives the other, and you wouldn’t know how far you could take something without finding basics, applying it, finding more basics, applying it. It’s amazing. If you ask me, when we started the Human Genome Project in the 1980s, would I have imagined where we are today? I’d say, “Not a chance.” Maybe off by a factor of 10 or a hundredfold.

Preet Bharara:              That’s a big factor. Can I ask what may be a silly question? Why would the focus at the outset have been on very rare diseases as opposed to common diseases?

Eric Lander:                  Ah, because rare diseases are easier. Science is the art of the practical. When you have a rare disease, cystic fibrosis, Huntington’s, they’re caused by a defect in a single gene, and tracing its inheritance pattern in the family, that’s pretty easy. You see how the disease goes down the family, you find some genetic spelling difference that shows the same pattern of inheritance in the family, and there you go. You know they must be pretty nearby and you can search the region. We know today that the common diseases that affect most people: schizophrenia, diabetes, heart disease, these are actually the products of hundreds, sometimes thousands, of genetic differences, each of which have much weaker effects.

Eric Lander:                  In the prehistoric days of the 1980s, we didn’t yet have the tools to imagine even that we’d be able to find all those pieces. So, you start with something you can do, and then you build to take on things that are much, much, much harder, and today we can do those things.

Preet Bharara:              Thanks for that explanation. Genes can be altered. Sometimes that happens naturally, they can mutate, and sometimes through application of certain systems and tools, they can be altered. Sometimes people use the verb edited. How does that work?

Eric Lander:                  Well, okay. You’ve now made a leap of a couple of decades from the concept of mapping-

Preet Bharara:              Because I only have an hour.

Eric Lander:                  No, no. I’m happy to make those leaps, but trying to fill in that transition there. A lot of the work, until relatively recently, has focused solely on finding the disease genes. In fact, there’s still a tremendous amount of that work still to go. Because, if we can find the genes that underlie a disease, we can figure out the processes of disease and how to fix them. It’s pretty much like if you have a problem with your car and you don’t know what parts are broken, it’s really hard to fix the car. The first important thing to do is pop the hood, look under the hood, figure out what parts are broken, and then go get new parts or add motor oil or something. Most of genetics is devoted to figuring out, “What’s the problem?” What’s the, what we’d call in biology, the process or pathway, and where’s there a problem with it?

Eric Lander:                  Now, once you know that, there may be a lot of ways to fix it. There are genetic diseases that can be fixed by diet. Famous example. There’s a genetic disease called phenylketonuria. Turns out people, the one in million babies who are born with that disease, can’t digest a certain nutrient called phenylalanine. You just put them on a diet that doesn’t have phenylalanine and they don’t become mentally retarded. That’s an example where a dietary solution might work.

Eric Lander:                  There are other diseases where a drug can be very helpful. Cystic fibrosis, the gene was discovered in the late 1980s. Took a couple of decades, but now there’s a pharmaceutical company that sells pills in a bottle that actually address the molecular defect, help fix the protein that is defective because of a genetic mutation, and that works very well.

Eric Lander:                  But there are going to be some cases, and that’s what you’re getting at with gene editing, where the solution is not going to come from a change in diet, and it’s not going to come a pill in a bottle, but the best solution might be replace the gene, or change the spelling of the gene. That’s a very different thing. That’s a Buck Rogers thing. It’s not eat some drug, it’s somehow get into the DNA sequence and change one letter out of the three billion letters of the genetic information, and do it not just in one cell, but maybe in the vast majority of cells in your body, or at least the cells in the relevant organ in your body. Maybe your lung if it’s cystic fibrosis, or your liver if it’s something else.

Eric Lander:                  I got to say, Preet, that in the 1990s non-scientists would always say, “Well, if you find the gene for disease, why don’t you just fix it? Why don’t you just change the DNA sequence?” As scientists, there’d be a tendency to, maybe a little condescendingly, explain to people that, “Well, you can’t do that. There’s no way to get into the cell and change the letters of the genetic instructions in just that right place in so many cells.” I think we all thought that was the case for a long time.

Preet Bharara:              When people were saying, “Why don’t you just do that?” The consensus, in the scientific community and including for you, was that was that was literally an impossibility?

Eric Lander:                  Yeah. The more you knew the less likely you thought that was. Because you have a DNA molecule, or set of molecules, that are three billion letters long. How in the world are you going to send instructions to one particular spot, at two billion, five hundred whatever million you ended up, a T there, and change it to an A. We didn’t even have an addressing system, a way to position the new instruction within a living cell. All of the work that had been done in molecular biology had really focused on DNA that was extracted from a cell. Cell’s dead, you got DNA in a test tube, you can futz around with it. But this was a question of, in a living cell, how are we going to do search and replace? In your word processor you could type in a word and say, “Find me all instances of Preet Bharara, and then I want to turn it into Tweet Bharara.” You could do that-

Preet Bharara:              That’s been, I think.

Eric Lander:                  … word processor. It’s been done, I’m sure, many times.

Preet Bharara:              In a manner of speaking.

Eric Lander:                  Because have a search and replace function. But there was no search and replace in living cells. Except it turned out there was. Bacteria had worked out how to do this more than a billion years ago. And, as usual, humans don’t invent stuff in molecular biology, we discover that bacteria had been doing it all along, and then we borrow it from the bacteria. It turns out bacteria have this as a defense mechanism. When they get attacked by viruses, they want to remember, “Oh, I’ve been attacked by this virus. It’s a bad thing,” so they developed a defense mechanism that knows how to look for particular sequences of DNA and do a search and cut function. Whenever you see this virus come in, cut it. It has a way to remember those sequences.

Eric Lander:                  Well, over the course of about 20 years, a set of scientists working in what were originally obscure corners of bacteriology, discovered this remarkable, I guess it’s like an immune system for bacteria. Just like if you’ve been infected you develop an immune memory, the bacteria were able to remember where to cut things. Once they understand how that worked, they could, number one, give it new instructions to have it cut anywhere. Just like your word processor, you could type in anything and it can do a search. Now, bacteria have a search protein, and it knows how to cut.

Eric Lander:                  The second hard part was, “Can you make it work not just in a bacteria where it was evolved, can you make it work in human cells?” By 2013, it was shown that you could transfer this machinery by making a few tweaks, maybe a lot of tweaks, but you could transfer it into human cells. That meant, suddenly, bursting on the scene in 2013, was the ability to take a human cell and make an edit at particular places, send it to a certain gene of your choosing, the hemoglobin gene, and say, “Cut here.” Or even replace the sequence by something else.

Eric Lander:                  All this is a long-winded way to say, “Search and replace on your word processor now can work in human cells for DNA because bacteria thought to invent it a billion years ago and it’s gotten repurposed.” Now, I don’t want you to get the idea it’s quite as simple as search and replace in a document because that’s really simple, but the concept is essentially identical to that, and more and more people are developing ways to say, “Deliver those search and replace instructions with a virus, make them more efficient.”

Eric Lander:                  Now, I’m required by being a scientist to tell it’s complicated, things can go wrong. Maybe the search and replace will sometimes make a cut at the wrong place, maybe it won’t always be efficient, maybe we can’t get it to the right cells. All sorts of people are working on ways to improve that, but it’s really opened up amazing possibilities in medicine.

Preet Bharara:              Can we just put it in context for a moment and bring some perspective to this? Some years earlier, before 2013, this was thought to be a medical and scientific impossibility. Then it was discovered that the opposite was true, and although it’s complicated and it’s still being tweaked, on the scale of scientific discovery, and with respect to disease in particular, how big and radical a development is this?

Eric Lander:                  Oh, very big and radical. I think it’s fair to say the idea that bacteria had a search and replace function that was programmable, and that it could be transferred to human cells and still work, is mind-blowing. That was the result of, this was not a, “Eureka,” moment, it was 20 years of work by a whole bunch of scientists in different countries around the world. But together, that ensemble of about a dozen or more people, changed the world by discovering and repurposing these mechanisms, and it was totally shocking that this could happen. What’s amazing, of course, the way science works these days, it went from being shocking to, oh, within two or three years, essentially every lab around the world routinely using it. We adjust very well to, “Oh my god, who thought this could possibly be done,” to, “Yes, of course, the new graduate student down the hall is using it for everything.”

Preet Bharara:              How scary is this, though? When you begin the conversation, you talked about taking drugs and changing your diet. That doesn’t seem so crazy. That’s not Buck Rodgers stuff. You invoked that old series. Should people be, at least initially when we get into some of the details of this and some controversies that have arisen over this process. But it sounds like frightening stuff, that humans can go into people’s genes and edit them.

Eric Lander:                  Well, you got to parse this out a little bit. If you’re talking about an existing patient with muscular dystrophy, who has a genetic defect that prevents them, the misspelling of a gene that prevents them from making an important muscle protein, and you would like to replace that protein by, say, bringing in a new gene into the cell or editing … That’s part of a set of ideas called gene therapy that have been around for a long time. This is a much better way to do gene therapy on a patient perhaps, but the concept of either replacing the protein or adding back a gene, people have been working on, that part isn’t so scary because … People might think, “Well, I can add genes and turn people into Marvel comics superheroes or something.” No, we don’t know how to do those things.

Eric Lander:                  What we can try to do is take a gene that isn’t working and replace it. For a living patient who is suffering from a disease, I would say taking a drug that fixes the problem or fixing the gene, aren’t ethically very different things. This information’s not passed on to the next generation, there’s person there who can consent to it, there’s an FDA that is going to make sure that it is safe and efficacious. I think the thing that people worry about, and I worry about, is taking the step to saying, “Should we do that on embryos? Should we edit an embryo?” That’s where I think people … because there you’re making genetic changes that are passed on to the whole population. You don’t have a sick patient, per se, you don’t have anybody who can consent to it. That’s a very different thing.

Eric Lander:                  I would distinguish between treating an existing patient, science has called this somatic gene therapy because somatic refers to your whole body versus germ-line gene therapy. Germ-line refers to the cells that are passed on and on to the next generations. It’s this germ-line editing that sits in a different place and really requires a lot of serious attention.

Preet Bharara:              Another basic concept or basic term that I want to address before we get into some more ethical issues. There is a mechanism called CRISPR which apparently is not a mechanism vegetables. It is something different. Can you explain what that is?

Eric Lander:                  It is.

Preet Bharara:              Can you explain what that is?

Eric Lander:                  Well, all this stuff we’ve been talking about, about this mind-blowing ability to edit genomes in living cells, is done with this bacterial system that goes by the name CRISPR. Why it’s called CRISPR? It’s a long, shaggy dog story having something with the structure, the bacterial sequence and its genome. Clustered Regularly Interspaced Palindromic Repeats, which will mean nothing to anybody, but it got abbreviated to CIRSPR, so we all call it CRISPR. But it’s just this gene editing thing-

Preet Bharara:              It’s just what we’ve been talking about.

Eric Lander:                  It’s all of what we’ve been talking about, goes by the name CRISPR.

Preet Bharara:              One thing that is fascinating about this is how we go about thinking about the ethical implications, and you’ve already begun to talk about some of it. My first basic question is, time is short, resources are limited, and complexity is there in different variations depending on the nature of the disease as you talked about. How does the scientific and medical community think about a newly discovered tool or mechanism like this, in terms of prioritizing efforts to fix certain diseases, or fight certain disease? In other words, there’s a million diseases, as you said before. Originally the Human Genome Project was about figuring out rare diseases because they’re simpler. Is that really the way that you prioritize now, going forward? Or is there some thought of, “Well, what is the disease that does the greatest harm, or that’s the most painful?” How do you think about that?

Eric Lander:                  Well, look. There’s a monolithic entity that decides what science gets done in America. There’s basic research, a tremendous amount of basic research of, “How do you do genome editing?” There are, oh, I don’t know, in the last year, three or four amazing new systems that use CRISPR in totally unexpected ways. The fundamental technology is rapidly progressing. There you have people who develop technology saying, “I think I have a cool idea. I’m going to find funding or use funding to develop it.” You want to have that explosion of creativity. You have a ton of people who are using CRISPR to study fundamental problems. You want to make a mouse that models a particular kind of cancer? That might have taken you three or four years to do that before, by adding genes to the mouse using old fashioned ways.

Eric Lander:                  But now, you can make five or six genetic changes simultaneously and get a mouse with this new genetic composition, you can do that in the matter of a month or so. This is dramatically accelerated fundamental biological research. Again, here, we’re not saying which disease or whatever. We have a large community of scientists and they’re trying it all over the place to get a better understanding of causes of disease.

Eric Lander:                  Really, when you get to the questions you’re asking, it’s about treating patients. Should one attempt a clinical trial to treat a patient who has, oh, a brain disorder or a liver disorder or a muscle disorder or an eye disorder? A lot of that, frankly, has to do with practical things. Can one deliver the CRISPR machinery to the right cell type? There are a lot of companies that are working on things like this, and this is a good place for me to note that there are a number of investigators at the Broad who have contributed to the discovery of all this CRISPR stuff, and have started companies. The Broad has licensed some of those things to companies. I don’t mean to run up the flag for any particular company, and I want a flag that because we have licensed it there are royalties that could come back.

Eric Lander:                  I want to just generally describe the field, but I got to at least make that statement which I always feel obliged to make, that all of these different groups are, in a way, competing, trying to choose the most useful application that they see based on how practical it is, based on whether you can really deliver based on whether there’s real patient need.

Preet Bharara:              Capitalism too, right, because these are for-profit enterprises?

Eric Lander:                  If you’re going to do this you’ve got to finance it, and either the NIH, the National Institute of Health would pay for a study, but that’s not so typical in something like this. It’s usually going to be done by startup companies.

Preet Bharara:              It’ll depend a little bit on market.

Eric Lander:                  It’ll depend on markets. Markets, of course, care about the practicality, they also care about whether there will be reimbursement for these. Some combination of scientific ideas and where one can get funding, will determine what are the first applications that are being tried. People want to do applications where they could see if it’s working or not working more quickly rather than less quickly. But there’s not any one person who’s deciding it. What we have is we have a whole society of marketplace and ideas that are testing things out. We’re at the stage where over the next several years we’ll begin to see some of these applications to inherited genetic diseases that will be tested in patients.

Preet Bharara:              How safe is this?

Eric Lander:                  Well, that’s one of the first critical things that you have to find out in any clinical trial. You want to ask, “If you try to edit this one letter, how often do you accidentally edit other letters in the genome?” What’s called off-target editing. Well, we can measure that in mice and we can measure it in cells, but one of the questions will be measuring it in human beings. The first part of a clinical trial is a safety study. There are questions if you mis-edit some other gene in the genome, could it, God forbid, lead to cancer? People worry about that. I think this is where it is really good that we have a Food and Drug Administration that is the best in the world and that is careful. These are amazing technologies, there are lots of cool applications, and they have to be done slowly and responsibly because you can always imagine ways that things could backfire.

Eric Lander:                  So, step one is prove safety, and then show that you get efficacy, that you could, say, take cells in the back of your eye, in the retina, that have some dominant mutation that will lead to blindness and knock out those genes. Every one of those studies, the question’s are going to be asked, “How are you going to know it’s working?” You can’t just willy-nilly squirt something into somebody’s eye and hope for the best.

Preet Bharara:              You think the FDA is competent and good about being able to regulate a new technology like this?

Eric Lander:                  FDA is a tradition whipping boy where people complain about the regulator. I got to say, in all of my experiences with the FDA, I have been deeply impressed that they understand the science, they understand the urgency for patients. They know patients want this. They also know that a lot of care is needed to do it. I watch them, every time I see the FDA I watch them thinking about how they sail between these two places of not being so caught up in the urgency that you’re not careful and not being unnecessarily cautious that you’re not going to be willing to allow proper experiments. It is a tough job, but I got to say, I have a lot of respect for our US drug regulator. They’re pretty smart and they’re pretty caring. I think they have served us well by letting things go swiftly but not recklessly ahead.

Preet Bharara:              That’s an interesting standard. Hard to define.

Eric Lander:                  But of course it’s hard to define. It’s a judgment call. You ask, “What’s the quality of the people making the judgment?” I think it’s tough. But the whole world looks to the USFDA for guidance. I think they are the regulator that sets the standard for the world.

Preet Bharara:              People are probably listening now, and the theory is interesting, and the generalized potential that we’ve been talking about is interesting. Is there anything you can say to folks about what particular usage in the near term is most promising? People who have a certain kind of genetic-based disease should be optimistic about? Or is it all too distant?

Eric Lander:                  The first thing that’s getting done is actually applications in cancer. Not to change anybody’s inherited disease genes, but to modify certain immune cells that will attack a cancer. There are these new immunotherapies to take your own immune cells and give them new instructions to attack certain proteins found only on the cancer. CRISPR has already entered the clinic for those applications.

Preet Bharara:              Which kinds of cancer?

Eric Lander:                  Oh, many different kinds of cancers. Using the immune system against cancer is a very general strategy. You’ll see it used in many ways. If you’re asking about editing inherited genes for diseases, either people thinking about sickle cell anemia, for example. I think there are people thinking about these inherited blindnesses. There are, oh, maybe a couple of dozen applications, and I think you will see clinical trials, and if they were to work you could see approvals easily within the next five years for some sets of genetic diseases. I always look much further out and ask, “When we really know what we’re doing, what will be the limiting step?” I think for these inherited genetic diseases, the big challenge will be delivering the genetic editing machinery to the right tissues. It’s not so easy to necessarily get it into the brain, and get it to the right cells. I’m already seeing a generation of scientists growing up who are thinking about these issues of delivery and other things.

Eric Lander:                  Now, I got to say, Preet, I take the position of trying very hard not to over-promise. I don’t want to promise, “Oh, there are going to be therapies for lots of things in the next five years.” Because I think over-promising is a really bad thing for science to do. What I can say is we made enormous progress in figuring out what are the causes of rare genetic diseases, and in the last six, seven years the causes of common genetic diseases. That’s shifted completely our ideas about what we would treat. Then, with tools like CRISPR and other things, we’re beginning to see how we could do it. So, if I look ahead over the next couple of decades, I could imagine that a significant part of therapies would not be a pill in a bottle, but at least in favorable cases, could be a genetic modification of cells in a certain place.

Eric Lander:                  I don’t think people should be running out expecting it next year, but I think, steadily, we’re going to see this a modality, as a method of treatment that we never had before. And if we’re really careful and we don’t screw up, it will work well and we’ll begin to understand how broadly we can use it. If that sounds like I’m being a little cautious and all that, that’s very deliberate [crosstalk 00:44:59]-

Preet Bharara:              Caution is good, mostly.

Eric Lander:                  Caution is good. The Human Genome Project was finished, a number of reporters wanted me to declare that, “Oh, disease would now be conquered.” No, no, no. What the Human Genome Project did give us the ability for the first time to peel back the curtain and see what was going on in disease. Now, that is a steady step on the path to conquering disease.

Preet Bharara:              Look, under-promise and over-deliver is a good mantra for scientists too.

Eric Lander:                  Exactly. That is exactly the thing. But, integrated over a long enough period of time, it’s stunning. You look at infectious disease, from the time that people discovered that bacteria cause infectious diseases, to the time that we had penicillin and other antibiotics at pennies a dose, that was probably 75 years. But it changes the world. That’s the kind of agenda we’re in. It’s not the agenda this news cycle or of any given political term, it’s the agenda that says, “If we can take on diseases, and it gets done in half a century or three quarters of a century, and our children and our children’s children never have these particular problems, I don’t think we have any apologies to make.”

Preet Bharara:              We’ve been talking about good things that CRISPR can do. What are some misuses, and should we be concerned about those misuses, and how much?

Eric Lander:                  Oh yeah, of course. I got to say that the other topic of editing babies, using CRISPR to do germ-line modification of embryos, has been a topic of enormous concern to the scientific community. If you want to prevent genetic diseases, you can already do that in many, many ways. The main reason that children with genetic disease are born to families today, is the family never knew they were carries. If you really cared about that, you’d start with genetic screening. We don’t have routine genetic screening. Beyond that, there’s something called in vitro fertilization with pre-implantation genetic diagnostics. That is, you do standard in vitro fertilization, you fertilize a bunch of eggs with some sperm, and you let them grow up a little bit in the Petri plate and you pull off one cell, and you ask, when you genotype that cell, “Is this embryo carrying the genetic disease or not?” And you just reimplant those that don’t carry the genetic disease.

Eric Lander:                  I have many colleagues even here at the Broad, who are carrying a genetic disease and they have healthy children who didn’t inherit it because they took advantage of in vitro fertilization with genetic diagnostics to just pick the embryos that wouldn’t inherit it.

Preet Bharara:              How expensive is that compared to using gene editing? What’s the cost of all this CRISPR stuff?

Eric Lander:                  Well, the CRISPR stuff would be done on in vitro fertilized embryos, so it’s an add on top of. It doesn’t avoid everything I just said because you would still have to fertilize, at least today, the way this is done, you still have to get eggs and sperm and grow them up, and then you would, say, CRISPR them. But people would say, “Maybe it’s just easier to just select the ones I want to reimplant.” For all these reasons, the scientific community has come together and said, “We really ought to have some clear understanding of when is it appropriate to even conceive of doing CRISPR editing of babies. And, what would be a responsible clinical path?” I told you all the considerations and clinical trials for a living patient with a disease. Well, what would the similar clinical trials need to be for this?

Preet Bharara:              There’s a particular incident that happened in China-

Eric Lander:                  There was an incident which made this far more salient. I think, for many people, it was was assumed that nobody would be so stupid, so unethical, as to try this until all this was worked out-

Preet Bharara:              And by this you mean engaging in gene editing of an embryo?

Eric Lander:                  Gene editing of an embryo. Exactly. And yet, there was a scientist in [inaudible 00:49:15] in China called [inaudible 00:49:17], and Dr. [inaudible 00:49:20] went ahead and genome edited two embryos and reimplanted them, and at least claims that two twin girls were born that were genome edited. The entire thing was broadly regarded as a total disaster. The particular genes that he was editing, it was really unclear why you would edit those genes. It was not clear there was much benefit. it appears there were great irregularities with getting ethical approvals for that. It was done in secret. The particular edits don’t seem to have worked out exactly right. Almost everything that could go wrong did go wrong.

Eric Lander:                  People were so shocked when this got announced about a year ago at a genome editing summit that was held in Hong Kong, that two different groups, the World Health Organization set up a panel of people to ask, “When should stuff like this be allowed?” A bunch of national academies of sciences in the US and the UK and many other countries, organized a commission to ask, “Under what circumstances is there even a responsible way to clinical trials of this?” As it happens, because it’s been a topic I’ve written about, I was asked to serve on that commission, so I am. I think our instructions are to come out with a report some time in the course of of 2020 trying to answer those questions about are there even responsible clinical paths. And, if so, for what applications? I have an open mind to all that but I certainly feel these are really, really important questions to get right, and rushing down the path of making permanent edits to the human gene pool that are passed on to the next generation. This is just something that we ought to be really thoughtful before starting.

Preet Bharara:              How do you regulate that?

Eric Lander:                  Oh, there are lots of regulations. In the United States it’s against the law.

Preet Bharara:              Did the gentleman in China break any law?

Eric Lander:                  Well, the problem is it’s a little complicated. I don’t think we all have a clear idea of how Chinese law applies in this case. The Chinese may not have either because the laws may not have been written for this purpose. I think it’s a wake-up call that people have to look and see. Most of Europe, that experiment would be illegal. United States it is absolutely illegal. In the UK you would need regulatory approval that would make this all very visible. They do allow certain types of embryo manipulations. Lots of the world has it.

Eric Lander:                  People say, “Well, how are you going to prevent a rogue scientist from doing this?”

Preet Bharara:              I was going to ask that.

Eric Lander:                  My answer is, yeah, the problem is, well, okay. You’re an attorney. How are you going to prevent anybody from ever murdering somebody else? You won’t. But you will have laws that make murder illegal and you’ll have few murders. If you ask here, “Is one rogue scientist the thing we’re worried about?” Is that going to really harm the world? Or, is what we’re worried about going down a path where thoughtlessly we agree to lots of genome editing and creating genetically modified babies. I’m much more concerned about the policies that nations adopt than that there could be rogue actors. Because rogue actors, as terrible, as unethical as that is, will do limited harm to specific individuals, and they should go to jail for it. I much more care about the policies that we adopt.

Preet Bharara:              Can I ask you an ignorant question based on watching science fiction films?

Eric Lander:                  Yeah.

Preet Bharara:              We talked about all the good uses, and to my uneducated mind, what all of this brings to memory from watching a lot of crazy movies, is can you edit genes to do things that are not related to disease, to make a population of people have a higher IQ, or be taller, or be stronger, or be able to run faster? Is that nonsense, or is that something that’s a real possibility in the future?

Eric Lander:                  It’s somewhere in between those two. It turns out that most of the traits you just talked about fall into that complex genetic bucket that are not single gene disorders. We know with height involves well over a thousand different genetic variants around the genome, so you might have to make a very large number of changes to have any significant impact. It’s not something that anybody should go try to do today. Is it possible sometime in the future? Well, you never want to rule out anything. The initial things will be directed at single gene things, but if you go far enough out, are there people who somewhere between hypothesize and hallucinate about, “Can we make human beings that are resistant to radiation for deep space flight?” People talk about such things. I’m not enthusiastic about seeing any of that start.

Preet Bharara:              Is that realistic?

Eric Lander:                  Well, nobody knows how they would do it yet. But there are some bacteria that are highly radiation-resistant so you can hallucinate that maybe we’ll figure out how to do that for human cells. This is the thing. If you look in nature, and you say, “I see something in nature, bacteria that are resistant to radiation, maybe I could repurpose it to humans.” When you say, “Is it realistic?” Is it realistic in the next 10 years? Absolutely not. Is it realistic in the next century? Maybe. Hard to know. I think that’s why we really have to get clarity as to what we’re doing, have a regulatory system, have ethical understandings, make decisions among nations, “Why do we want to do these things?” The future’s a very long time, many things can happen, and I think we have to lay firm regulatory and scientific and ethical foundations going forward.

Preet Bharara:              How do you rate the United States in terms of innovation in this field, in genetics?

Eric Lander:                  Well, a tremendous amount of the innovation of actually applying CRISPR in human cells has come from the United States. A lot of the discovery of this system in bacteria, that came from many different countries. I got to say, that was really an international ensemble that did that. But a tremendous amount of the innovation around repurposing these systems to humans and to applying them to diseases, the innovative energy is in the United States. Now, that’s not to say there’s not a lot of important work going on elsewhere, but disproportionately in the US.

Preet Bharara:              Are there any particular innovations in the near term that you’re excited about and that people may not be so aware of?

Eric Lander:                  Well, I mean, there’s a lot of innovations that to a geeky scientist are so cool. In the past month a colleague of mine here at the Broad Institute and at Harvard published a nifty new way to do CRISPR genome editing where you can add back lots more information and you have even better control. I know of more such things that will be coming down the pike from different people. At the level of a scientist, every couple months something really amazing comes along.

Eric Lander:                  At the level of the kinds of decisions that we should be making as a society to choose our world and try to take advantage of the upsides of this without creating dystopian downsides, I think the questions are pretty squarely on the table, and it’s time to sit back calmly and think through, “What are our values? What are our tools for doing this? What kind of international conversation has to go on?” Because it’s one human race, one human species, and we want to be able to have international conversation around it. I think those questions are posed and the nifty scientific advances don’t really change the fundamental issues. These are going to be about values, and sometimes conflicting values. I’m not saying these are easy questions, that’s why I’m trying to pay a lot of attention on this commission, but they’re really about values that persist over time.

Preet Bharara:              I don’t want to let you go without talking just for a few minutes about the area where science intersects with law enforcement, the latter of which is my expertise. You have a lot of experience there and you’ve served on bodies and people watch television, they watch CSI, and often there is scientific evidence and testimony relating to science. The one that people are most familiar with is, in recent years, DNA testing. Which I think everyone agrees if done properly is pretty much fool-proof. Correct?

Eric Lander:                  Well, as long as properly is defined properly, yes.

Preet Bharara:              But unlike other kinds of science that I think you’ve also written about and talked about, whether you’re talking about hair analysis and hair identification and some other things, DNA is superior.

Eric Lander:                  Oh yeah. Look, back in 1989 I, through a series of accidents, got involved in a case in the Bronx, People v. Castro in New York state. It was one of the first cases in which DNA evidence came in. There, it was practiced so sloppily as to be just abominable. The evidence got thrown out and it led to … I was pro bono expert witness in that case-

Preet Bharara:              For the defense?

Eric Lander:                  For the defense. I insisted on not being paid for this thing because I think this was about scientific integrity. There’s a long shaggy dog story here because all of the experts who testified for the defense got together during the course of this pre-trial hearing and met with all the experts who had testified for the prosecution-

Preet Bharara:              Without the lawyers, right?

Eric Lander:                  Without the lawyers. And we persuaded them to switch sides. They eventually agreed that the evidence was terrible. This was science at its best. Science is sitting around a conference room looking at the evidence and saying, “No, this stuff is just terrible.” On the strength of the fact that no remaining witnesses were left other than the testing lab itself that had brought the evidence, the judge rightly concluded that DNA, fingerprinting, as practiced back then was not admissible into courts because it was terrible. That led to a lot of improvements and standards and National Academy committees and other things. Because DNA was based on first-rate science it was possible to have that technology respond to the point today where a DNA sample from a single individual can be reliably, definitively identified and matched to another sample. It gets more complicated if you have mixtures of DNAs from lots of different people, or tiny amounts of DNA, but basically DNA can be done very, very, very well. But the surprise was that once we something that was an honest to God gold standard, you could go back to cases where people had been convicted on other forensic evidence, like hair, for example.

Eric Lander:                  Some examiner had come into court and said, “Oh, I put the hair from the defendant under the microscope and I compared it to the hair found at the scene of the crime, and they are identical. It turns out, we now know because you can take the little DNA that’s found at the base of the hair and run it, that, say, in the FBI’s own crime lab. When they said it was an identical match, about one time in nine it was just not the same person. One time in nine is a really significant error rate. If you told a jury, “Oh, the scientific examiner for hair said these were identical, that might override all other evidence in the case because it must be that that was the defendant at the scene of the crime. But if you told the jury, “Oh, and by the way, they get this wrong about one time in nine.” Suddenly that piece of evidence is very different.

Eric Lander:                  Well, this is the problem. We now know that for lots of other kinds of forensic evidence other than DNA that’s been used for decades. Sometimes it’s more than half a century. They get it wrong. It turns out, shockingly, I say this in jest, every forensic technology is not perfect. The only way you can know how good it is is by testing it, by blindly giving examiners large numbers of cases where you know the right answer and they don’t know the right answer, and empirically finding out how often do they get it right. This is the most obvious thing in the world, that the only way a forensic technology should be validated enough to come into court is that you’ve empirically tested it. In the scientific community this was settled in the 1600s, that empirical testing is the only thing that we should believe.

Eric Lander:                  But we have a lot of technologies in the courts that have never been subjected to empirical testing because they were admitted by court 40 years ago and because of the great respect for precedent that courts have, they say, “Well, it was admitted before, it should be admitted again.” It’s very hard to force people to do empirical tests. Ballistics, you fire a bullet from a gun. Because in the last couple of years people have done the experiment, we find out it’s pretty good, but they get it wrong and they get it wrong at a rate more than one in 100. Sometimes one in 60. Even fingerprints, which the FBI declared to be infallible in a document it issued in the 1980s, the FBI itself ran a brilliant study where they measured the rate of error in fingerprints. They found it wasn’t zero. It was a number. It was pretty good. It was one of the several hundred.

Eric Lander:                  So, for all these reasons, what DNA has told us is that the courts have been very accepting of forensic technologies without meaningful scientific evidence. I think a lot of us feel like anything that comes into court wearing the mantle, the robe of science, claiming all of the trappings of science, ought to have to live up the standards of science.

Preet Bharara:              Yeah. Look, it’s very easy to be overwhelmed by that, by something cloaked in the language of science. Fingerprints also. I have a chapter in my book where I talk about a very famous misidentification of a fingerprint of somebody who the FBI thought was responsible for the killings of 191 in that Madrid train attack-

Eric Lander:                  Brandon Mayfield.

Preet Bharara:              Brandon Mayfield, and they got it wrong.

Eric Lander:                  I know it well.

Preet Bharara:              I spent a lot of time on that case in my book. They got it wrong. But everyone is blinded … The experts say, “Well, this is science. You have to accept it. That’s not my opinion.” It causes people to forget question maybe the methods by which they were doing it, the standards that they were observing, and the methodology. It’s not perfect.

Eric Lander:                  This is a topic I think we both care a lot. The law does have rules, and we know there’s this rule that says the evidence has to be based on reliable principles and methods that have been reliably applied, the federal rules of evidence. The battle here is what does it mean to have reliable principles and methods that have been reliably applied? I think a lot of people in science, and this was something I’ve worked on, say that word reliable means empirical testing. There is no reliability based on anything other than I actually tried it and I measured it. That turns out shockingly to be controversial in the forensic community. I hope, in the long run, we overcome that because forensics will get better and better when it holds itself to those standards. That’s what we’ve learned from science. Even if you’re frustrated that you find out your method wasn’t as good as you thought, once you can measure its accuracy you can make it better.

Preet Bharara:              The nature of genius and the nature of scientific genius is very elusive and hard to understand. But you’ve been a scientist for a long time and have been part of discoveries and innovations. Do you have a theory of what qualities are in people who are capable of innovation and scientific discovery? What’s the DNA of an innovator?

Eric Lander:                  Okay. Couple of things. I’m not a particular fan of using words like genius because that suggests that the people are-

Preet Bharara:              Did you reject the grant you got?

Eric Lander:                  You’re referring to this MacArthur grant.

Preet Bharara:              Which is also known as the-

Eric Lander:                  Genius Award. But not by the MacArthur or by me.

Preet Bharara:              All right.

Eric Lander:                  That’s what the press dubs it. The MacArthur know better than to call this a genius award.

Preet Bharara:              [crosstalk 01:06:09]. No further questions.

Eric Lander:                  No further questions. Thank you, counselor. No, I think when you label some people geniuses it’s very off-putting to others. I don’t think it’s about genius and I don’t think it’s necessarily in your DNA too. I think both of those suggest that it’s inherent. I actually think that scientific discovery, scientific innovation, even really bold stuff, comes from other things, and a lot of those get learned. A willingness to float ideas, lots of ideas, because most ideas will be wrong and people who, when the float a wrong idea, then feel bad and don’t float more ideas, well, they’re cutting themselves off from what is the real secret of innovation, which is persistence and ideas, trying lots of things. I think being able to feel comfortable with being wrong and just putting yourself out there, helps a lot.

Eric Lander:                  I think the other thing that helps a lot is coming with a new perspective to a problem. The greatest progress is usually made by somebody who’s coming from one field and looking at a problem in a way nobody’s ever looked before. If you’re the 20th person to look at something the same way, it’s really tough to come up with something truly novel. But if you’re bringing an insight from engineering to biology, or from mathematics to somewhere else, it turns out to be easier. A lot of it is looking differently at problems.

Eric Lander:                  I think there’s a whole list of things that are teachable and that we fail to teach people about how to be a good scientist. In our schools, what we try to do is is teach people to memorize factoids in the textbook so that they can answer the problems. That’s nothing like science. Science is about playing around and looking for patterns, learning to ask good questions, failing, bringing a new perspective to something. Because I see people around the Broad Institute. We have an amazingly innovative, brilliant community, and I got to say, I can think of 50 different kinds of scientists here who look totally different in the way they approach things. That’s why I reject this idea that there’s genius, or it’s in your DNA, I think this is a question of, “How do you make great baseball players?” I don’t believe all great baseball players are born, I think they grow up in environments where baseball is a loved activity and they put a lot of time and effort into it. They learn how to do it, and they talk to other people how to do it.

Eric Lander:                  We would be wrong to imagine that doing science is reserved to some small set of people. I think most children are natural scientists. They are curious about the world. they ask a zillion questions. they want to experiment. I think we actively, in many cases, drive that out of them. That’s a real shame because I think the natural human condition is to be a scientists and an explorer, and we just have to learn how to help people cultivate that fabulous love.

Preet Bharara:              Well, I can’t think of a better note to end on. Dr. Eric Lander-

Eric Lander:                  Well, it’s great to talk to you.

Preet Bharara:              Thanks for being on the show. I really appreciate it. That was a pleasure.

Eric Lander:                  Really fun. Take care, Preet.

Preet Bharara:              That’s it for this episode of Stay Tuned. Thanks again to my guest, Eric Lander.

Preet Bharara:              Hey folks. I hope everyone had a wonderful, fabulous, amazing New Year’s Eve. I myself am recording this before New Year’s. It’s Monday, December 30th, and I’m in my hotel room in Jerusalem. Some of you know I’ve been traveling in Jordan and in Israel and seeing a lot of different things, with my family. I’m here with my wife and kids, also my parents. My dad turned 80 just a short while ago so we thought a family vacation would be a good idea. There are three generations of Bhararas here. We’re soaking up history, soaking up culture, learning about religion, and also a lot about conflict and war.

Preet Bharara:              I essentially had two goals for this trip. One was to shut out the news and not pay too much attention to American politics and the news cycle that drives us all crazy all year long, refresh and reenergize and clear my head. And the other was to learn about the things that I’m seeing here in Jordan and Israel. We’ve done a lot of that. We hung out in the desert, we went to the Israeli Supreme Court, we went to the [inaudible 01:10:49], we saw Temple Mount, the Dome of the Rock. We’ve been to the Western Wall. We went to Bethlehem, the birthplace of Christ. And we’ve been overwhelmed by the history. We’ve also been consuming a lot of food that might fit on the plane back. But it’s not been fully possible to ignore the news coming out of the United States. Because some has penetrated and I think requires comment, especially given where I am. It’s terrible and heartbreaking. I’m talking, of course, about the recent rash, wave really, of anti-Semitic violence, hate crimes, intolerance, not here in the Middle East, but back home in New York.

Preet Bharara:              In the last number of days there have been a series of attacks, hate crimes, perpetrated against people in the Jewish community. There have been stabbings. Also an anti-Semitic failed shooting in Jersey City at a kosher supermarket. Nine or 10 awful events just in the last couple of weeks. Then, on Saturday, there was a horrific event in Monsey, New York where a man barged in on a group of observing Orthodox Jews celebrating Hanukah. He stabbed five of them, sending several to the hospital. One, I believe, still remains in critical condition. And why did he do it? Because they were Jewish. Monsey, New York is in Rockham County, which is within the jurisdiction of my old office, the Southern District of New York.

Preet Bharara:              The SDNY has filed a five-count criminal complaint against the perpetrator, charging, essentially, a hate crime. More specifically, obstruction of free exercise of religion, and involving an attempt to kill. According to the complaint, the perpetrator used a machete, a long knife. Also according to the complaint, the perpetrator kept a journal in which there were all manner of anti-Semitic references. The investigators also discovered that on his phone, he had conducted certain searches, including, “Why did Hitler hate the Jews?” And also, “German Jewish temples near me.”

Preet Bharara:              I want to thank my old office, the FBI, the state police, and the NYPD, for all their great work. This should be prosecuted as a hate crime. That’s good. Hate crime is among the worst kinds of crime. It may be the most insidious criminal cancer you could have in a tolerant society. It is hatred attached to violence, it’s a form of terrorism. It’s an accusation of otherness. It’s an incitement to other people. It’s also an invitation to hateful copycats. It’s intolerable. Prosecution can bring justice, it can bring accountability and punishment.

Preet Bharara:              But prosecution doesn’t cure hatred, it doesn’t always bring peace. It doesn’t bring harmony and tolerance, not by itself. I’ve been a prosecutor most of my adult professional life, but I know the limits of what the law can do. We all have a responsibility in our society and in our culture, to not tolerate it, to not laugh it off, to not perpetuate it. We have a responsibility to teach our kids, to teach our neighbors, not to hate. And, when things like this happen, especially when they seem to come as a wave, it affects not just the Jewish community, it affects every community, and no community is safe. We should try to be as honest as possible about what causes it and who the perpetrators are. They’re not always white nationalists. We need to condemn it no matter who you are or what community you you’re from, and call for greater understanding.

Preet Bharara:              The NYPD says, “Hate crimes against the Jewish community are up 18%.” That’s a lot. This Thursday, my last day with my family in Israel, the day the podcast will drop, we’re visiting [inaudible 01:14:07]. As you know, Israel’s memorial to victims of the Holocaust. I want to be careful not to too quickly invoke Hitler and the Holocaust, but never forget, means something, for all of us. One resolution I have is that in the coming year on this podcast and in other places, I want to talk more about hate, explore the origins of hate and what we can do about it. Because politicians will come and go, but the things that fester in people’s hearts, hatred and racism and anti-Semitism, those things can fester for a long time. It doesn’t always take a politician to bring them out.

Preet Bharara:              We all need to figure out a way to create an environment that is intolerant of intolerance. Let’s all commit ourselves to that.

Preet Bharara:              If you like what we do, rate and review the show on Apple Podcasts, or wherever you listen. Every positive review helps new listeners find the show. Send me your questions about news, politics, and justice. Tweet them to me at Preet Bharara with the hashtag askpreet. Or, you can cal and leave me a message at 669-247-7338. That’s 669-24PREET. Or you can send an email to [email protected] Stay Tuned is presented by CAFE The executive producer is Tamara Sepper. The senior audio producer is David Tatasciore. The Cafe team is Julia Doyle, Calvin Lord, David Kurlander, and Geoff Isenman. Our music is by Andrew Dost. I’m Preet Bharara. Stay Tuned.