Unlocking Gene Therapy with Gaurav Shah

Are rare diseases themselves rare? Neil deGrasse Tysonand comedian Chuck Nice learn about the science of gene therapy and how it can treat and potentially cure rare diseases with Gaurav Shah, CEO, Rocket Pharma.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Neil deGrasse Tyson?

  Coming up on StarTalk, we feature my interview with the CEO and co-founder of Rocket Pharma. This is a company in New Jersey that specializes in finding cures for genetic ailments using gene therapy. More on that, coming up.

• 0:21Neil deGrasse Tyson?

  Welcome to StarTalk, your place in the universe where science and pop culture collide. StarTalk begins right now.

• 0:35Neil deGrasse Tyson?

  Alright, let's get this party started. I don't know if we would have done this if the name of your company didn't have the word Rocket in it.

• 0:42Chuck Nice?

  I know, I know.

• 0:43Neil deGrasse Tyson?

  So, so if I...

• 0:45Chuck Nice?

  Yeah, you know, before this, we got duped into doing something for Rocket Mortgage.

• 0:52Speaker 02

  It's R K T, not R C K T.

• 0:54Neil deGrasse Tyson?

  Okay, got it. Well, different, different ticker.

• 0:56Speaker 02

  Different ticker, yeah, exactly.

• 0:58Neil deGrasse Tyson?

  Um, so, in fact, I have a hundred questions for you. And I was just wondering, the fact that you had a telescope as a kid and... So you have, you have a science geek underbelly within you, astro-science geek underbelly. So, would you have rather have been an astrophysicist? Like, did you just stumble into this field?

• 1:21Chuck Nice?

  Yeah, what are you, what are you doing wasting your life on this crap?

• 1:26Neil deGrasse Tyson?

  Saving lives!

• 1:27Chuck Nice?

  Saving lives and curing diseases!

• 1:30Neil deGrasse Tyson?

  Yeah, you could have been completely useless like the rest of us. What's the...

• 1:35Speaker 02

  You know, I grew up in Fort Worth, Texas, and...

• 1:37Neil deGrasse Tyson?

  Fort Worth?

• 1:38Speaker 02

  Yeah, there's a lot of spelling bee nerds that come out of there for some reason.

• 1:41Neil deGrasse Tyson?

  Is that right?

• 1:42Speaker 02

  I think most winners come from Fort Worth. It's like this really weird thing. But the son of Indian immigrants who came from India and wanted the best for us. Um, you only have three career choices, really. It's medicine, engineering, and I'm not sure what the third one is. There's a... right, so, um, and, uh, so, but I also, you know, it was a science theme that pervaded the first several years of my life, whether it was astronomy or medicine. And I loved both. Actually, in my first year of college, though... I was an astronomy major under John Huckstra.

• 2:15Neil deGrasse Tyson?

  Oh, yes.

• 2:16Speaker 02

  Years ago, but I changed.

• 2:17Neil deGrasse Tyson?

  John Huckstra.

• 2:17Speaker 02

  Huckstra, Huckstra, yes.

• 2:18Neil deGrasse Tyson?

  Yeah, yeah. It's at Harvard.

• 2:19Speaker 02

  Yeah.

• 2:19Neil deGrasse Tyson?

  It's a way to take his saying he went to Harvard.

• 2:22Speaker 02

  I was trying.

• 2:23Neil deGrasse Tyson?

  That's how that, you do that, you know? Okay.

• 2:26Chuck Nice?

  Not to be confused with the John Huckard of Rutgers.

• 2:31Speaker 02

  I, um, I was trying to be quiet about it.

• 2:34Neil deGrasse Tyson?

  Yeah, yeah.

• 2:34Speaker 02

  You and me.

• 2:35Neil deGrasse Tyson?

  Friend and colleague. Yes. No, so, so I'm delighted to learn that the universe was part of what excited you to be a scientist, to go into science fields. And, um, then there's this thing about a Grammy. So you're also a musician. And what I'd like to know, just to start off before we get into the nitty gritty here, would you say your career in music, your side career in music, mattered or contributed to your inspirations or curiosity in the sciences?

• 3:09Speaker 02

  I think they're all sort of the same, is what I would say. I think, uh, whether...

• 3:15Chuck Nice?

  Tell that to your mother when you come home saying you want to be a musician.

• 3:19Speaker 02

  Actually, I did, and it didn't work out so well.

• 3:21Chuck Nice?

  Yeah, I'm sure that conversation didn't go very well.

• 3:23Neil deGrasse Tyson?

  No, it did not.

• 3:24Speaker 02

  I ended up marrying a musician, and that's, you know, that's one step removed. But, uh, you know, so it worked out. Um, but I think they're all the same. I think that, uh, whether it's music, or astronomy, or medicine, there's a sense of feeling connected to other people, feeling connected to something greater, uh, for making sure that we don't feel alone in the universe. I think that's the connection between these, these disciplines.

• 3:52Neil deGrasse Tyson?

  Interesting. So if, not to put words in your mouth, but you're suggesting, I think correctly and accurately, that art is a force of nature unto itself that serves to bring humans together. Not only the artists themselves, but those who might not have such talent, but they are nonetheless touched by the art.

• 4:12Speaker 02

  Absolutely. Actually, when we're in a band and we're performing, it doesn't matter where you're from, doesn't matter what language you speak, uh, it doesn't matter how old you are. Um, it real, everyone becomes a fellow musician.

• 4:26Neil deGrasse Tyson?

  A participant in the experience.

• 4:28Speaker 02

  And you're seeking something that's bigger than the band.

• 4:30Chuck Nice?

  But it does matter which one of you has a fallback in science.

• 4:38Chuck Nice?

  So that you will not be sleeping on your friend's couch.

• 4:41Neil deGrasse Tyson?

  Right, right.

• 4:41Chuck Nice?

  At age forty-five.

• 4:43Neil deGrasse Tyson?

  Right, right. And which is why there are street musicians, but there aren't street scientists.

• 4:50Chuck Nice?

  Right.

• 4:51Neil deGrasse Tyson?

  To just think that through.

• 4:52Chuck Nice?

  Exactly.

• 4:53Neil deGrasse Tyson?

  That's right.

• 4:54Chuck Nice?

  I'll calculate for a dollar.

• 5:00Neil deGrasse Tyson?

  So would you say, given this beautiful reference to humanity and our connectivity within us, would you say you approach your science with an artistic lens? Or do you approach your art with a science lens?

• 5:15Speaker 02

  It's both. Great, I love the question.

• 5:17Neil deGrasse Tyson?

  It's a two-way lens.

• 5:18Speaker 02

  It really, I don't think these are that separable, in my view. And I'll give you specific examples. In gene therapy, the way that gene therapy works is that there's a viral vector and a transgene that carries the corrected DNA to the patient's cells, right? And in figuring out how to create that vector, you can create a million types of vector, and only one will be the best one. And how do you know? We can predict, you can use AI, you can use mathematics, various models to figure out that you need the right promoter, the right length, cut out the stuff that doesn't matter. At the end of the day, there's an art to it, there's a music to it.

• 6:01Speaker 02

  And what's actually going to work is what the intersection of that vector and the patient and that patient's body, which is a musical, artistic thing, less scientific. In the same way, when one is learning music, you have to be rigorous, rational, practice over and over again, and really, really think. It's a cerebral thing to really learn music, until you get to a point where it's natural and it's distinctive. So I don't think there's that much of a difference.

• 6:29Neil deGrasse Tyson?

  All right. Now, you mentioned gene therapy.

• 6:34Neil deGrasse Tyson?

  Could you, let's do gene therapy 101 for the moment. It's for me, and I don't, maybe Chuck knows.

• 6:40Chuck Nice?

  Well, I already know what gene therapy is.

• 6:43Neil deGrasse Tyson?

  It's for other people.

• 6:44Chuck Nice?

  Yeah, I mean, maybe the people out there who work for the company might want to know.

• 6:49Chuck Nice?

  You know, I mean, you have some genes, they lay on the couch.

• 6:54Chuck Nice?

  They talk about their gene mother.

• 6:57Neil deGrasse Tyson?

  So, so, you know, we, many of us have heard of gene editing. And so maybe, let me start with the question. Can you distinguish for us, for me, between gene editing and gene therapy?

• 7:10Speaker 02

  Absolutely, and I know you've done a podcast with Jennifer Doudna.

• 7:14Neil deGrasse Tyson?

  Yes, we did, yeah.

• 7:15Speaker 02

  Which I saw, which was really fabulous and, and much to learn from. So, think of your whole genome like a book. And what gene editing does is, it finds a word that was misspelled, whites it out, and writes in the correct word. Right? Each page is a gene, so you edit, that's called gene editing.

• 7:37Neil deGrasse Tyson?

  You said whites it out?

• 7:39Speaker 02

  Yeah, like white out. Whites it out.

• 7:42Neil deGrasse Tyson?

  Just kidding. If everyone younger than 30 in this room, there used to be a typewriter, and paper, and ink.

• 7:53Speaker 02

  I know, right.

• 7:54Neil deGrasse Tyson?

  Okay. And then there was this liquid. Okay.

• 7:59Speaker 02

  They still have it in Texas, that's for sure.

• 8:01Neil deGrasse Tyson?

  Okay, so you would, you would blot it out?

• 8:05Speaker 02

  Blot it out, and you write or type in the correct word. And what we do, traditional gene therapy is, you add the whole page with the corrected word in it. You just add the whole gene back, instead of trying to edit it individually with individual letters, words. So that's the difference.

• 8:22Neil deGrasse Tyson?

  Why, what, isn't that harder? To put all the genes back than just fix one of them?

• 8:26Speaker 02

  We can create the gene in a lab, basically, with the whole sequence intact, and you don't have to edit. It's the scissors and editing part that's hard. Right, just replacing the whole thing is actually really much easier, and...

• 8:42Neil deGrasse Tyson?

  That I didn't know.

• 8:43Speaker 02

  Right, and, and gene editing is, is starting to work. There's a company that just released a product in sickle cell disease just a week ago. So it is starting to work. But traditional gene therapy is here for so many patients who need it now. There's ways to replace genes that will work for cardiac and hematology diseases, and reach these patients who are otherwise gonna probably die pretty soon, without waiting for gene editing.

• 9:10Neil deGrasse Tyson?

  So if you do this, you swap that out? Again, I'm still in gene 101 here. Every one of my cells has my entire genome in it, correct?

• 9:21Speaker 02

  Yeah.

• 9:22Neil deGrasse Tyson?

  Okay, so what does it mean to swap it out here when I have all the rest of my body's cells? Are you going into every one of my body's cells to do this?

• 9:30Speaker 02

  So there's something called tropism. The attraction for the viral vector.

• 9:35Neil deGrasse Tyson?

  Tropism? What'd he say?

• 9:37Chuck Nice?

  I'm a gene. I'm just a gene. Very good, Gene. Very good. The best. The best, Gene.

• 9:47Neil deGrasse Tyson?

  Alright.

• 9:52Speaker 02

  So the tropism...

• 9:54Neil deGrasse Tyson?

  Tropism.

• 9:54Speaker 02

  Tropism is the attraction of a vector, and I'll come back to a vector.

• 9:59Neil deGrasse Tyson?

  You loving yourself some vectors here.

• 10:00Speaker 02

  Yeah, I love vectors, yeah. For a particular cell type. For example, there is a vector called AAV. AAV9 specifically that loves the heart.

• 10:10Chuck Nice?

  See, I got heart socks on today.

• 10:12Speaker 02

  Um, yeah. That loves the heart, and it's tropic for the heart. So it primarily will take the corrected gene to the heart, not to all the cells in the body. That's essentially how it works.

• 10:23Neil deGrasse Tyson?

  Oh, so...

• 10:24Chuck Nice?

  So now, when you do this, let's... Does there have to be a problem? Or can you identify the potential of a problem? Change the page? And then, once you do that, will I then pass that corrected gene on to my offspring?

• 10:41Neil deGrasse Tyson?

  That's my next question.

• 10:42Speaker 02

  Yeah, so right now...

• 10:44Chuck Nice?

  Wow, we've been working together too long, man.

• 10:46Speaker 02

  No, so, uh, gene therapy right now... Gene therapy and gene editing is directed towards somatic cells. So only cells that are already fully developed, not germ-lined cells. There may be a day when you want... When we want to correct our disease and also make sure that our offspring don't have it. But the first step is to correct the individual's disease. That's what we're focused on right now, and probably for the foreseeable future.

• 11:10Neil deGrasse Tyson?

  It seems to me if you're really good at that, then you don't have to correct it at the germ level. Because you just do it any time it comes up, you just do it.

• 11:21Speaker 02

  Yeah.

• 11:22Neil deGrasse Tyson?

  You go to the hospital and then go home, and then you're done.

• 11:24Speaker 02

  That's right, and Chuck, you also asked the question, do you do it after there's disease or before? Right. So with our trials, we have to start in a setting where the disease is already present. Right, someone, for example, we have a drug in a certain form of devastating heart failure called Danone Disease. We want to wait right now until patients actually manifest Danone Disease, because you don't want to treat somebody unnecessarily while still being tested.

• 11:47Neil deGrasse Tyson?

  Is there somebody named Danone?

• 11:49Speaker 02

  There is a Dr. Danone who also came to a seminar just like this a couple of years ago. And it's his disease?

• 11:54Neil deGrasse Tyson?

  That's what I'm saying.

• 11:55Speaker 02

  He discovered it.

• 11:56Neil deGrasse Tyson?

  Let me tell you some advice here, okay? I was once, got a phone call, said we'd like to name an asteroid after you. After you, and I, my next question was, is it headed towards Earth?

• 12:08Neil deGrasse Tyson?

  You don't want asteroid Tyson to take out civilization. So they said, oh, no, it's safe in the asteroid belt. So I said, thank you. So, so, so to have a disease that is especially lethal with your name on it, doesn't sound like an honor.

• 12:22Speaker 02

  Unless Dr. Tyson was gonna also help steer the asteroid away from Earth. Right. Which is what Dr. Danone did. Ah, that sounds like the volunteer firefighter who started the fire.

• 12:34Neil deGrasse Tyson?

  Oh!

• 12:37Neil deGrasse Tyson?

  That's right.

• 12:40Speaker 02

  Yeah, no, so Dr. Danone's a wonderful person. He discovered the disease, but he also helped us uncover the solution for it.

• 12:47Neil deGrasse Tyson?

  Okay, so now, you, you have, um, you're using viruses for this. Because they're kind of badass at what they do, right? And so you're, you're recognizing this fact. So how do you know which virus to use of the countless ones that we share this planet?

• 13:06Speaker 02

  Yeah, that, that's been a journey of probably three decades of earlier discovery before we, we got to this place. Uh, we use two types of viruses. One is a lentivirus, which is a modified HIV virus. We know how infectious HIV can be, but we're inactivating it and making sure that it doesn't self-replicate, but still infect cells.

• 13:27Neil deGrasse Tyson?

  That's a good thing, yeah.

• 13:27Speaker 02

  Right, so still infect cells. Um, and that's good for bone marrow diseases, hematology conditions. Sickle cell is actually one of them. A, a hematology disease where something like lentivirus would be good. And another virus we use is called AAV. Adeno-associated virus, and AAV is non-infectious, but also can infect cells pretty robustly. And we use that for our cardiac diseases, as well as other companies have worked on CNS and liver and other diseases using AAV. So you select the virus based on the target organ, again, where it would be most tropic for.

• 14:02Neil deGrasse Tyson?

  So you're turning... It reminds me of a quote from Abraham Lincoln. And he said...

• 14:07Speaker 02

  Nice.

• 14:09Neil deGrasse Tyson?

  Can we not defeat our enemies by making them our friends?

• 14:14Speaker 02

  Friendemies?

• 14:15Neil deGrasse Tyson?

  Well, no, no, that's different.

• 14:16Speaker 02

  Yeah, that was Real Housewives.

• 14:20Neil deGrasse Tyson?

  No, the point is, you have viruses, and none of us thinks nice things about viruses. You turn them into something that can help us. And then viruses become our friends.

• 14:30Speaker 02

  Actually, for folks who are right now potentially cured of their hematologic diseases like Fanconi anemia and LED, which we're working on, those viruses are their friends.

• 14:54Speaker 03

  Hello, I'm Vicky Barok Allen, and I support StarTalk on Patreon. This is StarTalk with Nailed Grass Tyson.

• 15:09Neil deGrasse Tyson?

  So you've said vectors at least 30 times in this conversation. So you have a virus that... And I have a cartoon understanding of viruses. There's a cell, there's a virus, and they'll only interact if there's a way for them to physically connect. And so can a virus otherwise just bust in to do its work? Or does it need some kind of backdoor or some kind of trapdoor that it knows about?

• 15:37Speaker 02

  A docking station.

• 15:38Neil deGrasse Tyson?

  Docking station? How does that work?

• 15:40Speaker 02

  I'm glad you say that. So, yes, there are protein-protein interactions on the surface of the virus and the surface of the cell. And that's exactly what tropism is. But taking maybe the cartoon...

• 15:49Neil deGrasse Tyson?

  Oh, so you're saying in tropism, it's not even biochemical, it's physical?

• 15:52Speaker 02

  Yes, yes.

• 15:53Neil deGrasse Tyson?

  That's what you mean by tropism? Oh, okay. The shapes match up, and then there you go.

• 15:58Speaker 02

  Exactly, exactly. But so it's like a dock, right? So think of a vector like a rocket.

• 16:04Neil deGrasse Tyson?

  There comes the rocket.

• 16:05Speaker 02

  Yeah.

• 16:05Neil deGrasse Tyson?

  And, uh... You knew that was coming.

• 16:08Speaker 02

  Listen, I wouldn't have it any other time. You're not surprised.

• 16:12Neil deGrasse Tyson?

  Exactly.

• 16:13Speaker 02

  Uh, the rocket, the vector is like a rocket. The gene that you're correcting is basically the cargo or the payload or even the people. Right? And you're basically, uh, you can use that analogy to think about gene therapy, right? Taking corrected gene into cells, just like a rocket takes people to wherever they want to go. Wherever... Where do you want to go, by the way?

• 16:33Neil deGrasse Tyson?

  I like Earth.

• 16:34Speaker 02

  You're fine, okay.

• 16:35Neil deGrasse Tyson?

  Yeah.

• 16:36Speaker 02

  You're fine.

• 16:38Neil deGrasse Tyson?

  Okay, so rocket is vectored, right? It has a direction and it has a purpose and a mission and the velocity.

• 16:45Speaker 02

  Right.

• 16:46Neil deGrasse Tyson?

  Okay, so...

• 16:48Speaker 02

  I was debating with some of my team about velocity as a value because we want to move fast, but they're like, "Well, rocket already has velocity, so it's sort of redundant." I said, "Fine."

• 16:57Neil deGrasse Tyson?

  Velocity can equal zero.

• 16:58Speaker 02

  Right.

• 16:59Neil deGrasse Tyson?

  Right, just to be clear.

• 17:00Speaker 02

  Good point.

• 17:01Neil deGrasse Tyson?

  V equals zero.

• 17:02Speaker 02

  Yeah. V equals zero, right? That's fine.

• 17:05Neil deGrasse Tyson?

  And velocity can even be negative as a vector, yeah.

• 17:08Speaker 02

  I stand down.

• 17:09Neil deGrasse Tyson?

  Okay. Yeah. Um, all right, so what, here's a big economic question. If there's a rare disease out there, what is your, other than the goodwill you might have, what is your financial incentive to invest people, time, energy, resources, venture capital, money, to cure that where you can run the math on it and it could never pay your bills?

• 17:41Speaker 02

  No critical math.

• 17:42Neil deGrasse Tyson?

  Unless you charge like a hundred million dollars per dose.

• 17:45Speaker 02

  Right.

• 17:45Neil deGrasse Tyson?

  Which is just absurd.

• 17:46Speaker 02

  Right.

• 17:47Neil deGrasse Tyson?

  And then you gotta hope that Jeff Bezos is the one who has the disease. Just write that check right there. So, so tell me, what is your relationship to this world of rare diseases and how does that make economic sense?

• 18:01Speaker 02

  Yeah, so I think someone who pursues rare disease is a rare individual. It takes a certain mission, passion-driven focus, science focus, um, and entrepreneurship to really go into rare disease. Bigger companies... Tend to shy away from rare disease because, to your point, it doesn't make business sense. But for a small company that's starting out, it makes total business sense.

• 18:24Neil deGrasse Tyson?

  You were publicly traded, but you'd still be counted as a small company.

• 18:26Speaker 02

  In my mind, we're a startup. Because the mindset of a startup is that everyone cares and we're all founders, we're all owners, and the patients and we are connected very personally. So even if we blossom into a much bigger company, we'll always be a startup in our mindset.

• 18:44Neil deGrasse Tyson?

  Keep telling yourself that.

• 18:45Speaker 02

  Yeah. 283 people here. I think we all feel that way.

• 18:51Neil deGrasse Tyson?

  28,000 people.

• 18:52Speaker 02

  Exactly. That is...

• 18:54Neil deGrasse Tyson?

  Okay, so a startup mentality, by the way, is one of the healthiest things that can exist in a growing economy. Because then ideas can germinate. They're not squashed by legacy of whatever people think should be true.

• 19:07Speaker 02

  Latitude to be creative.

• 19:09Neil deGrasse Tyson?

  All of that. We're loving that. So, all right, I looked at some numbers before I got here. I did a little bit of homework. And there's a website that is all about rare diseases. What is it, the National... N O R D? NORD, NORD. See, everybody here knows NORD. And what I noticed is there are so many rare diseases that the rare disease category is almost as big as any other diseases that are not rare. In other words, rare diseases are not rare.

• 19:48Speaker 02

  As an aggregate.

• 19:49Neil deGrasse Tyson?

  In the aggregate, is that...

• 19:51Speaker 02

  It's funny you say that. Yeah, so each rare disease is rare, but rare disease is not rare.

• 19:54Neil deGrasse Tyson?

  Yeah.

• 19:55Speaker 02

  And, yeah, they're...

• 19:56Neil deGrasse Tyson?

  As a category.

• 19:56Speaker 02

  As a category. That's exactly right.

• 19:58Neil deGrasse Tyson?

  If you bust in and you're good at rare diseases, that is... And it's the tactics that you invoke, which could have specificity depending on the disease, but the methods and tools are similar. Oh my gosh, you can corner the market on rare diseases.

• 20:13Speaker 02

  Yeah, so actually, in...

• 20:15Neil deGrasse Tyson?

  I shouldn't have said it that way, that's so trash.

• 20:17Speaker 02

  Oh no, it was great.

• 20:18Chuck Nice?

  This is America.

• 20:19Speaker 02

  Part of the market.

• 20:20Chuck Nice?

  We are totally fine with what you just said. We know exactly what you said.

• 20:24Neil deGrasse Tyson?

  No, it's corner the market is so trash, but okay.

• 20:27Speaker 02

  The reality is that this, developing these therapies does take a lot of money and requires investment and it requires dedicated investors who are here long term. Also, the government has a program called Pediatric Review Voucher Program that will reward companies who just get an approval for a rare disease, you know, so it sort of helps offset some of those costs so that there's a nice partnership there between industry and regulators.

• 20:51Neil deGrasse Tyson?

  You would expect, at some level, the government to step in if something's not otherwise financial, if it cares about its own citizens.

• 20:58Speaker 02

  Correct.

• 20:59Chuck Nice?

  And are there, are there residual or tertiary kind of benefits that come out of the specificity? When you, when you solve, it's very specific, can you then say, oh, all these other, you know, areas are now helped?

• 21:19Speaker 02

  Absolutely, so, we, here at Rock.

• 21:22Neil deGrasse Tyson?

  What you're trying to say is, can one thing help other things, is that what you're...

• 21:26Chuck Nice?

  Basically, yes, can one thing help other things?

• 21:28Speaker 02

  Another way to say it is, we have a platform approach. So, once you figure out one solution for a cardiac disease, it's easier to apply other therapies to other cardiac diseases. We recognize that, so does the FDA, by the way, they're trying to make things easier for us through both clinical and manufacturing, sort of streamlining.

• 21:46Chuck Nice?

  And when, and when you discover that help in the other areas, do you get a cut of that as well?

• 21:54Neil deGrasse Tyson?

  Probably if it's patented, right?

• 21:55Speaker 02

  Right. Yeah, I mean, we have some folks here who know quite a bit about FTO, freedom to operate and patents, but I think that the profitability here takes a long time as a startup. Some of the most successful companies are only profitable about eight years after their biggest launch, so that's gonna take time, but we're really here for the passion, the mission, and ultimately, the money will follow the science.

• 22:20Neil deGrasse Tyson?

  So, right now, are you, are you tracking cer- you have certain specialty diseases you're, you're targeting? What, what are they?

• 22:25Speaker 02

  So, we have six diseases that we target, three of them are bone marrow derived, which are Fanconi Anemia, a disease of DNA repair, the DNA, DNA actually can't repair itself. Carl Sagan and you had an episode with this DNA repair mechanism, right? So this is faulty in Fanconi anemia. I remember that from when I was eight and then again when I was a little bit older and watching your Cosmos.

• 22:50Neil deGrasse Tyson?

  You had a pretty good graphic on that.

• 22:52Speaker 02

  You did, yeah.

• 22:52Neil deGrasse Tyson?

  Yeah, yeah, that's right.

• 22:53Speaker 02

  Better than, should I say better than the original? But that was a long time ago.

• 22:56Neil deGrasse Tyson?

  Yeah, yeah, the original was 1980.

• 22:58Speaker 02

  Let's hope, let's hope.

• 22:59Neil deGrasse Tyson?

  Yeah, 44 years ago. Um, so just a quick point, I just slipped this in there.

• 23:04Speaker 02

  Please.

• 23:04Neil deGrasse Tyson?

  Um, what I did know about, I took biology as a senior in high school, which is very inverted from what was typical at the time, I think even today. I took physics first, then chemistry, then biology. So biology for me was more, I'll do it because I have to, right? But there's some things I remembered that the DNA molecule is actually handed. So if you put a DNA molecule in a mirror, those are not the same molecules. So, because it turns the other way. And so, one of the early versions, because the artists were, the, the, the computer graphic folks were creating the DNA molecule, and it was spinning the wrong way. I said, "No, that's not on this planet."

• 23:48Speaker 02

  Oh, wow.

• 23:48Neil deGrasse Tyson?

  Okay?

• 23:49Speaker 02

  Yeah, yeah.

• 23:49Neil deGrasse Tyson?

  Yeah, yeah, so the DNA molecule spins sort of helically clockwise if you're looking up from below. And it'll do that no matter how you orient it. So, I'm just proud of myself.

• 24:00Speaker 02

  Into that.

• 24:01Neil deGrasse Tyson?

  Yeah, a little applause for that, I think, but thank you. Okay.

• 24:06Speaker 02

  That's great.

• 24:06Neil deGrasse Tyson?

  That's my little, I like pyrality and handedness and things like that. Uh, but, uh, back to the point. So you were listing your disease that you focus on.

• 24:16Speaker 02

  Yeah, so Fanconi anemia is actually exactly, one of those molecules doesn't work in Fanconi anemia. One of those repair pathways doesn't work. So these patients develop bone marrow failure and leukemia in their teen, uh, single-digit years in their teens. So we have a therapy in Fanconi anemia that is going to be submitted to the FDA for approval first half of 2024. Um, just quickly, LAD1 is a disease, an infectious disease that, um, really kills little boys and girls by the age of two in two-thirds of cases. So it redefines the word devastating. They're in and out of hospitals with fungal pneumonias. Uh, and we've now treated nine patients. All of them are out about two years or more. And instead of living till the age of two, they may turn 92.

• 25:01Speaker 02

  In fact, our... Treating doctor who works with us, and we didn't say this because we can't, said this is a cure. Right? At the DNA level, correcting the DNA is the most fundamental way that we can cure disease as as human beings as we see it, right?

• 25:16Neil deGrasse Tyson?

  Right.

• 25:16Speaker 02

  Third one is called pyruvate kinase deficiency. It's like a hemolytic anemia, like a sickle cell or like a beta thalassemia. Then we have three cardiac programs that our company is the first one to get into that space. Danin disease, which I mentioned, a disease of the heart where these boys, more than girls, but boys, pass away in their teenage years as well of cardiomyopathy. Sometimes you hear about these athletes who suddenly fall over. Now we know why some of them fall over. They have something like Danin disease. Or PKP2 is another arrhythmia or back three. So we're really uncovering the fact that a lot of what we call traditional disease like heart disease or even stroke or Alzheimer's is actually many diseases.

• 26:00Speaker 02

  And we're trying to go after them one by one genetically.

• 26:02Neil deGrasse Tyson?

  So and you're targeting childhood diseases.

• 26:04Speaker 02

  Yes.

• 26:05Neil deGrasse Tyson?

  That's the greatest loss of life is the death of a child is in the statistics of population.

• 26:11Speaker 02

  That's right.

• 26:11Neil deGrasse Tyson?

  Right. I mean, you die at 80 because of, okay, you lost 10 years tops.

• 26:17Chuck Nice?

  And can any of these applications have relevance in chronic lifestyle diseases, which is what we see most of in America?

• 26:28Speaker 02

  Yes, there are some folks working on preventing coronary artery disease through a similar gene pathway. Where people are working on Alzheimer's. Huntington and Parkinson are already targets. So the way we see it is that we want to crack open the door based on single gene defects, right? Like the ones I mentioned or like sickle cell. And that'll ultimately-

• 26:53Neil deGrasse Tyson?

  They're at least tractable, right?

• 26:54Speaker 02

  They're tractable, yes.

• 26:55Neil deGrasse Tyson?

  If there's something that has 32 genes going on, you're in a, you can't.

• 27:00Speaker 02

  Right. So we start with one. We'll get to two. Eventually we'll be able to tackle many genes. But that's a ways away. And I think we're just trying to get the process-

• 27:08Neil deGrasse Tyson?

  Well, how ways away is it if we have AI plus quantum computing? That could be next, next-

• 27:14Chuck Nice?

  It won't make a difference because it will kill us all.

• 27:22Speaker 02

  2001.

• 27:23Neil deGrasse Tyson?

  Exactly. Oh, you're saying the AI will use the... The AI will use the... To be especially effective. There, there you go. Okay, okay, I take it back. I take back the question then. Chuck is right.

• 27:33Speaker 02

  I hope in our lifetime, but certainly in some of our children's lifetime, I think we'll see a lot of progress.

• 27:55Neil deGrasse Tyson?

  Alright, so, so if you are in the same field, even though it's specifically different swapping out whole pages of DNA, nonetheless, you are changing, or you would say restoring, but it's still changing the DNA profile you had before you walked into the room. Now, in your cases, it's kind of, the morality of it is trivial. The kids are gonna die, okay? But there are many genetic disorders, we call them, where you can still live a full life. It's just you don't match up with the model human, who you compare, all your senses and all your limbs, and are they all to match the model human? Well, then you're normal, alright?

• 28:40Neil deGrasse Tyson?

  And if you don't match it, then you're not normal. Like baldness. So, so where, where does, who says what's normal? And what's not?

• 28:51Speaker 02

  I mean, I think that...

• 28:52Neil deGrasse Tyson?

  Before 1987, I read that the American Psychiatric Association had, until then, had classified homosexuality as a brain disorder. And so, if it's a disorder judged by some committee of people, then who is deciding who gets gene therapy and who doesn't?

• 29:14Speaker 02

  Yeah, well, I think what's normal is probably defined by the times and by the culture.

• 29:21Neil deGrasse Tyson?

  Should it be?

• 29:22Speaker 02

  Maybe, maybe not. But I can tell you what's not normal is...

• 29:26Neil deGrasse Tyson?

  Because I know 170 years ago, what was considered normal in the United States in the South, okay?

• 29:31Speaker 02

  And 170 years from now, it might be that much different, right? But I know what's not normal, right, which is having these devastating diseases. I don't think that's normal.

• 29:43Neil deGrasse Tyson?

  Death.

• 29:43Speaker 02

  Yeah, death, I guess, is normal, but... Well, no. Yes. But not in young days. Not at two years old. We can all agree that's not normal. But yeah, I think that you're talking about designer gene therapy, and that's obviously somewhat of a controversial topic that's going to evolve over time. But I think we start where we start and then see where it goes.

• 30:05Neil deGrasse Tyson?

  No, because I say that, and I didn't come up with this. I mean, I see it rising up around me. What's the film?

• 30:13Speaker 02

  Gattaca.

• 30:13Neil deGrasse Tyson?

  No, no, I know Gattaca. No, no, it's the film that had...

• 30:20Neil deGrasse Tyson?

  It was a rock musician who went deaf. The Sound of Metal.

• 30:24Speaker 02

  Sound of Metal.

• 30:25Neil deGrasse Tyson?

  In that, it's a rock performer, and he, you know, he plays loud rock music, and then he goes deaf, pretty catastrophically. And then he learns that there's a whole community of deaf people, I'm summarizing here. And, but then they find a way that they could put devices in and have restore some of the hearing. And then, but he'd gotten so accustomed to the silence and the community of others who embraced that state of existence, that, no, he ultimately rejected it. Again, that's a case where he's otherwise healthy, just one of his senses is gone.

• 31:05Neil deGrasse Tyson?

  And so, I wonder where the future of this goes? And what kind of future?

• 31:17Neil deGrasse Tyson?

  You know, is there a sort of morality committee? Is there a, or in your field? Surely, there's something going on in the genetics.

• 31:24Chuck Nice?

  But that would be such a great thing. Because in order to get where you just said, Neil, we would have to be so advanced.

• 31:32Neil deGrasse Tyson?

  Oh, right. We would have cured all diseases.

• 31:34Chuck Nice?

  That all the disease would not, nobody would care about the disease anymore. Because we would be to a place where we're now worried about, why is everybody having white babies?

• 31:48Neil deGrasse Tyson?

  And just, and one other example. Um, we, Oliver Sacks was a guest on one of our earliest episodes of StarTalk. Uh, I got to befriend him briefly. We weren't beer-drinking buddies, but he's a neuroscientist, bestselling author. The movie Awakenings was based on his research. Uh, had Robin Williams in it, brilliantly acted in that role. Um, I attended a lecture he gave on, I think it was hallucinogenics or something. He's a brain guy. And, but he, he reminded us of his neurological condition. So he has, I forgot the full word, but the, for regular people, word. He has face blindness. Okay?

• 32:29Neil deGrasse Tyson?

  Where you don't recognize people's faces, even if you know them well. And so I would then realize that he would only recognize me after I started speaking. Be polite as a new shake hands, and then I'd speak, oh, yes, Neil, how are you? Okay. So, I asked him, if we developed a pill, a magic pill, and you could take it back in time, you could take it when you were a kid, to cure you of this, would you? And he said, no, he wouldn't. Because that very affliction in his mind is what got him interested in neuroscience to begin with. And so I think to myself, again, if we're gonna compare ourselves to some, like, model

• 33:10Neil deGrasse Tyson?

  homes, you have a model human, if you want everything to be, quote, "normal", that might eviscerate civilization of the most interesting people our genome can produce.

• 33:21Speaker 02

  And, and to bring it back to music, I would say some of the most creative geniuses of our time and previous times weren't completely normal.

• 33:31Neil deGrasse Tyson?

  You know, and, and, you know, they were challenged, they were troubled. Vincent van Gogh among them? Van Gogh, Mozart. Not that it's a prerequisite, but it's not, it doesn't preclude Right. that you can be highly creative and productive. Correct.

• 33:46Chuck Nice?

  I think that that is a outworking of being challenged, in a way.

• 33:51Neil deGrasse Tyson?

  Yes, yes.

• 33:52Chuck Nice?

  So, you know, but.

• 33:52Neil deGrasse Tyson?

  Because even if you're normal and you're not challenged.

• 33:55Chuck Nice?

  Right.

• 33:55Neil deGrasse Tyson?

  Then what, what do you have to overcome?

• 33:57Chuck Nice?

  Exactly.

• 33:58Neil deGrasse Tyson?

  Right.

• 33:58Chuck Nice?

  So, I mean, you can say the same thing about poverty, but does that mean that you don't want to end poverty? I mean, there are many people who will tell you that if it were not for the humble beginnings from which I came, I would not be the person that I am today.

• 34:13Neil deGrasse Tyson?

  Right.

• 34:13Chuck Nice?

  And I say to them, that's not necessarily the case. There could have been some other stimulus that would have sparked in you whatever motivated you to become what you are. So it's not, it's, it's, it's what we know that made us. It's what we know, so we say it because that's what we know. But we don't know what could have also been.

• 34:36Neil deGrasse Tyson?

  Sure. So, is the FDA your friend or your enemy? Ooh, wow. Turn off the cameras. I was gonna say. Turn off the cameras. I was like, I thought this was a friendly discussion.

• 34:50Neil deGrasse Tyson?

  Absolutely. Let me, let me ask it a different way. Is the FDA more stringent about their tests than most, if not all, other countries? And is that a good thing? I think they are, and I think that's a good thing. Yeah, okay. I think, especially. Speaking as a scientist. As a scientist, yeah. The results have to, have to work. They, they've got to be statistically right. Especially given how susceptible we are to thinking something that's true that isn't. Yeah. Or thinking that something isn't true that is. Yeah. That is, that is rampant.

• 35:18Chuck Nice?

  Optimism bias, yeah.

• 35:20Neil deGrasse Tyson?

  Yeah, yeah, yeah, the, the, what's it called? Um.

• 35:23Chuck Nice?

  Confirmation bias.

• 35:23Neil deGrasse Tyson?

  Confirmation bias. Thank you.

• 35:25Chuck Nice?

  But there is an optimism bias as well.

• 35:26Neil deGrasse Tyson?

  Yeah, yeah, in, in testing, yes. Yeah. Okay, so given that. Yeah, yeah. Uh, what, how does one get access?

• 35:35Neil deGrasse Tyson?

  I mean, there's a price. You're a publicly traded company, so all your stuff is gonna cost money. And I can't afford it, and I have a kid who's dying. So what do I do? Don't take this personally.

• 35:44Speaker 02

  No, so, the question, another way to think about the question is, what is the cost of not giving a life-saving therapy? And what is the cost to that individual, that family, and to society? And regulators and payers can come up with a price that makes sense, that's based on the magnitude of clinical benefit. Those are discussions that we're...

• 36:08Neil deGrasse Tyson?

  And insurance companies.

• 36:08Speaker 02

  Insurance companies, payers, exactly, right. So insurance companies will ultimately agree to be payers for that therapy because of the data they see. And that's discussions that we're starting to have now. And to answer the FDA question, they're absolutely friends. When we go to FDA meetings, sometimes you can't figure out who's from the company and who's from the FDA. They're helping us, we're helping them.

• 36:28Neil deGrasse Tyson?

  That's a good fact.

• 36:29Speaker 02

  It's...

• 36:30Neil deGrasse Tyson?

  They're not on the other side of some wall.

• 36:32Speaker 02

  Yes.

• 36:33Neil deGrasse Tyson?

  They're a participant in finding the solution.

• 36:35Speaker 02

  And they're people also, they have children. And I think, once you understand that this is, we're learning together, it opens up the doors. And, you know, again, going back to curiosity and wonder, I think, we go into the room with a sense of wanting to learn, and the outcome has always been great.

• 36:53Neil deGrasse Tyson?

  So, as a, this is only a question I can ask of a CEO. How do you measure your risk factors? Because in space launches, you know, Elon Musk has been very public about his launches where they blow up on the launch pad, right? And I spent a fair amount of time working with NASA, I was on their board for a while. And there was always someone in the room who was afraid that if the public saw a rocket blow up, or some major mistake, that somehow they'll withdraw the funding. And my reply to that was, as

• 37:31Neil deGrasse Tyson?

  an educator, you need to teach people that the day you stop making mistakes is the evidence you're not on the frontier. And so the public needs to be sensitized to what risk means here. Risk doesn't mean never anything going wrong. Risk means sometimes stuff goes wrong and then, provided you learn from that, that's all a good thing. So how do you, in terms of R and D, because you don't even have product yet, you said, right? Okay, so there's R and D versus profit versus all of this? And how risk averse are you?

• 38:08Speaker 02

  Yeah, we need, I think the secret sauce here is the right people, world-class people who are gonna believe and stay and persevere with grit and tenacity over time.

• 38:20Chuck Nice?

  Way to suck up to your employees.

• 38:24Speaker 02

  Inspire me more than I inspire them.

• 38:26Neil deGrasse Tyson?

  Chuck, we are their guests here, okay?

• 38:30Chuck Nice?

  I'll behave, I'll behave.

• 38:31Speaker 02

  We need patient investors who believe in the story. And yes, mistakes are a part of this. And since we're talking about these fields all mixing together, in the world of music, I've had the chance to sit and learn from real, really great masters as a musician. And the best masters? I sing Indian classical music and I play this instrument called the harmonium.

• 38:52Neil deGrasse Tyson?

  Oh, interesting, okay.

• 38:53Speaker 02

  But the greatest masters are the least judgmental. That's what I've learned. And even when you play a wrong note, they'll consider it musical because they hear what no one else hears. And I think that's the same with making mistakes in science. There's no right or wrong. You have to make mistakes. And I actually applaud SpaceX as, you know, being open about it and not fearful about it.

• 39:15Chuck Nice?

  Yes, I do too because I am not buying a ticket.

• 39:21Neil deGrasse Tyson?

  I told Elon, I say, "I'll ride one of your rockets after you fly your mother on one of them."

• 39:25Speaker 02

  There you go.

• 39:26Neil deGrasse Tyson?

  Safely, then I'll, then I'll, then I'll go.

• 39:30Neil deGrasse Tyson?

  I hope you enjoyed my conversation with Ourof Shah, the co-founder and CEO of Rocket Pharma, giving us a glimpse into the future of gene therapy. This has been StarTalk. And I've been your host, Neil deGrasse Tyson. As always, keep looking up.