SPEAKER_1: Coming up on StarTalk, we feature my interview with the CEO and co-founder of Rocket Pharma.
SPEAKER_1: This is a company in New Jersey that specializes in finding cures for genetic ailments using gene therapy.
SPEAKER_1: More on that coming up.
SPEAKER_1: Welcome to StarTalk, your place in the universe where science and pop culture collide.
SPEAKER_1: StarTalk begins right now.
SPEAKER_1: All right, let's get this party started.
SPEAKER_1: I don't know if we would have done this if the name of your company didn't have the word rocket in it.
SPEAKER_2: I know.
SPEAKER_1: So if I...
SPEAKER_3: Yeah, you know, before this, we got duped into doing something for Rocket Mortgage.
SPEAKER_3: It's RKT, not RCKT.
SPEAKER_1: Oh, different ticker.
SPEAKER_2: Different ticker, yeah, exactly.
SPEAKER_1: So, in fact, I have a hundred questions for you.
SPEAKER_1: And I was just wondering, the fact that you had a telescope as a kid, so you have a science geek underbelly within you, astro science geek underbelly.
SPEAKER_1: So would you have rather been an astrophysicist?
SPEAKER_1: Like, did you just stumble into this field?
SPEAKER_3: Yeah, what are you doing wasting your life on this crap?
SPEAKER_1: Saving lives.
SPEAKER_3: Saving lives.
SPEAKER_3: Curing disease.
SPEAKER_1: You could have been completely useless like the rest of us.
SPEAKER_1: What's the...
SPEAKER_2: You know, I grew up in Fort Worth, Texas.
SPEAKER_3: Fort Worth?
SPEAKER_2: Yeah, there's a lot of spelling bee nerds that come out of there for some reason.
SPEAKER_2: Is that right?
SPEAKER_2: I think most winners come from Fort Worth.
SPEAKER_2: It's like this really weird thing.
SPEAKER_2: But the son of Indian immigrants who came from India and wanted the best for us.
SPEAKER_2: You only have three career choices, really.
SPEAKER_2: It's medicine, engineering, and I'm not sure what the third one is.
SPEAKER_2: Right?
SPEAKER_2: So...
SPEAKER_2: And so...
SPEAKER_2: But I also...
SPEAKER_2: It was a science theme that pervaded the first several years of my life, whether it was astronomy or medicine.
SPEAKER_2: And I loved both.
SPEAKER_2: Actually, in my first year of college, though, I was an astronomy major under John Huxtra.
SPEAKER_1: Oh, yes.
SPEAKER_2: Years ago.
SPEAKER_2: But it changed.
SPEAKER_1: John Huxtra.
SPEAKER_1: Yeah, yeah.
SPEAKER_1: That's at Harvard.
SPEAKER_1: It's a way to take...
SPEAKER_1: He's saying he went to Harvard.
SPEAKER_1: That's how that...
SPEAKER_1: You do that, you know?
SPEAKER_2: I was trying to say...
SPEAKER_3: Not to be confused with the John Huxtra of Rutgers.
SPEAKER_2: I was trying to be quiet about it.
SPEAKER_3: Yeah, yeah.
SPEAKER_1: John Huxtra was a friend and colleague.
SPEAKER_1: Yes.
SPEAKER_1: No, so I'm delighted to learn that the universe was part of what excited you.
SPEAKER_1: What excited you to be a scientist, to go into science fields.
SPEAKER_1: And then there's this thing about a Grammy.
SPEAKER_1: So you're also a musician.
SPEAKER_1: But 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?
SPEAKER_2: I think they're all sort of the same, is what I would say.
SPEAKER_2: I think, whether...
SPEAKER_3: You talk to your mother when you come home saying you wanted to be a musician.
SPEAKER_2: Actually, I did, and it didn't work out so well.
SPEAKER_3: Yeah, I'm sure that conversation didn't go very well.
SPEAKER_3: No, it did not.
SPEAKER_2: Marrying a musician, and that's, you know, that's one step removed, but you know, so it worked out.
SPEAKER_2: But I think they're all the same.
SPEAKER_2: I think that whether it's music or astronomy or medicine, there's a sense of feeling connected to other people, feeling connected to something greater, for making sure that we don't feel alone in the universe.
SPEAKER_2: I think that's the connection between these disciplines.
SPEAKER_1: Interesting.
SPEAKER_1: So, 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.
SPEAKER_1: Not only the artists themselves, but those who might not have such talent, but they are nonetheless touched by the art.
SPEAKER_2: Absolutely.
SPEAKER_2: Actually, when we're in a band and we're performing, it doesn't matter where you're from.
SPEAKER_2: It doesn't matter what language you speak.
SPEAKER_2: It doesn't matter how old you are.
SPEAKER_2: Everyone becomes a fellow musician.
SPEAKER_1: A participant in the experience.
SPEAKER_2: And you're seeking something that's bigger than a band.
SPEAKER_3: But it does matter which one of you has a fallback in science.
SPEAKER_3: So that you will not be sleeping on your friend's couch at age 45.
SPEAKER_1: Right, right.
SPEAKER_1: Which is why there are street musicians, but there aren't street scientists.
SPEAKER_3: To just think that through.
SPEAKER_3: I'll calculate for a dollar.
SPEAKER_1: So would you say, given this beautiful reference to humanity and the connectivity within us, would you say you approach your science with an artistic lens or do you approach your art with a science lens?
SPEAKER_2: It's both.
SPEAKER_2: I love the question.
SPEAKER_3: So you're looking at a two-way lens.
SPEAKER_2: I don't think these are that separable, in my view, and I'll give you specific examples.
SPEAKER_2: 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?
SPEAKER_2: 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.
SPEAKER_2: And how do you know?
SPEAKER_2: We can predict.
SPEAKER_2: You can use AI.
SPEAKER_2: 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.
SPEAKER_2: At the end of the day, there's an art to it.
SPEAKER_2: There's a music to it.
SPEAKER_2: 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.
SPEAKER_2: In the same way, when one is learning music, you have to be rigorous, rational, practice over and over again and really, really think.
SPEAKER_2: It's a cerebral thing to really learn music until you get to a point where it's natural and it's distinctive.
SPEAKER_2: So I don't think there's that much of a difference.
SPEAKER_1: All right.
SPEAKER_1: Now, you mentioned gene therapy.
SPEAKER_1: Could you, let's do Gene Therapy 101 for the moment.
SPEAKER_1: It's for me and I don't, maybe Chuck.
SPEAKER_3: Well, I already know what gene therapy is.
SPEAKER_1: It's for other people.
SPEAKER_3: Maybe the people out there who work for the company might want to know.
SPEAKER_3: You know, I mean, you have some genes.
SPEAKER_3: They lay on the couch.
SPEAKER_3: They talk about their gene mother.
SPEAKER_1: So, you know, many of us have heard of gene editing.
SPEAKER_1: And so maybe, let me start with the question.
SPEAKER_1: Can you distinguish for us, for me, between gene editing and gene therapy?
SPEAKER_2: Absolutely.
SPEAKER_2: And I know you've done a podcast with Jennifer Dowd which I saw, which was really fabulous and much to learn from.
SPEAKER_2: So think of your whole genome like a book.
SPEAKER_2: And what gene editing does is it finds a word that was misspelled, wipes it out, and writes in the correct word, right?
SPEAKER_2: Each page is a gene.
SPEAKER_2: So you edit.
SPEAKER_2: That's called gene editing.
SPEAKER_1: You said it wipes it out?
SPEAKER_2: Yeah, like white out.
SPEAKER_2: Wipes it out.
SPEAKER_2: Oh, yeah.
SPEAKER_1: Just kidding.
SPEAKER_2: I threw up.
SPEAKER_1: If everyone younger than 30 in this room, there used to be a typewriter and paper and ink.
SPEAKER_2: I know, right.
SPEAKER_1: And then there was this liquid.
SPEAKER_2: Mm-hmm.
SPEAKER_2: They still have it in Texas, man.
SPEAKER_1: That's for sure.
SPEAKER_1: Okay, so you would blot it out.
SPEAKER_2: Yeah, so you blot it out and you write or type in the correct word.
SPEAKER_2: And what we do, traditional gene therapy, is you add the whole page with the corrected word in it.
SPEAKER_2: You just add the whole gene back instead of trying to edit it individually with individual letters.
SPEAKER_1: Oh.
SPEAKER_2: So that's the difference.
SPEAKER_1: Isn't that harder to put all the genes back than just fix one of them?
SPEAKER_2: We can create the gene in a lab, basically, with the whole sequence intact.
SPEAKER_2: And you don't have to edit.
SPEAKER_2: The scissors and editing part, that's hard.
SPEAKER_2: Right, just replacing the whole thing is actually really much easier.
SPEAKER_1: That I didn't know.
SPEAKER_2: And gene editing is starting to work.
SPEAKER_2: There's a company that just released a product in sickle cell disease just a week ago.
SPEAKER_2: So it is starting to work.
SPEAKER_2: But traditional gene therapy is here for so many patients who need it now.
SPEAKER_2: There's ways to replace genes that will work for cardiac and hematology diseases and reach these patients who are otherwise going to probably die pretty soon without waiting for gene editing.
SPEAKER_1: So if you do this, you swap that out.
SPEAKER_1: Again, I'm still in Gene 101 here.
SPEAKER_1: Every one of my cells has my entire genome in it, correct?
SPEAKER_1: So what does it mean to swap it out here when I have all the rest of my body cells?
SPEAKER_1: Are you going into every one of my body cells to do this?
SPEAKER_2: So there's something called tropism, the attraction for the viral vector.
SPEAKER_2: Trumpism.
SPEAKER_1: He said...
SPEAKER_3: I'm just a gene.
SPEAKER_3: Very good, Gene.
SPEAKER_3: Very good.
SPEAKER_3: The best.
SPEAKER_3: The best, Gene.
SPEAKER_2: So the tropism is the attraction of a vector, and I'll come back to a vector.
SPEAKER_1: You're loving yourself with vectors here.
SPEAKER_2: Yeah, I love vectors, yeah.
SPEAKER_2: For a particular cell type.
SPEAKER_2: For example, there's a vector called AAV, AAV9 specificity, that loves the heart.
SPEAKER_2: I got heart socks on today.
SPEAKER_2: That loves the heart, and it's tropic for the heart.
SPEAKER_2: So it primarily will take the corrected gene to the heart, not to all the cells in the body.
SPEAKER_2: That's essentially how it works.
SPEAKER_3: So when you do this, 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?
SPEAKER_1: That's my next question.
SPEAKER_2: So right now…
SPEAKER_3: Wow, we've been working together too long, man.
SPEAKER_2: No.
SPEAKER_2: So gene therapy right now, gene therapy and gene editing, is directed towards somatic cells, so only cells that are already fully developed, not germline cells.
SPEAKER_2: There may be a day 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.
SPEAKER_2: That's what we're focused on right now and probably for the foreseeable future.
SPEAKER_1: 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.
SPEAKER_1: You go to the hospital and go home and then you're done.
SPEAKER_2: That's right.
SPEAKER_2: And Chuck, you also asked the question, do you do it after there's disease or before?
SPEAKER_2: So with our trials, we have to start in a setting where the disease is already present.
SPEAKER_2: For example, we have a drug in a certain form of devastating heart failure called Dannon disease.
SPEAKER_2: We want to wait right now until patients actually manifest Dannon disease because you don't want to treat somebody unnecessarily while still being tested.
SPEAKER_1: Is there somebody named Dannon?
SPEAKER_2: There is a Dr.
SPEAKER_2: Dannon who also came to a seminar just like this a couple of years ago.
SPEAKER_1: And it's his disease?
SPEAKER_1: That's what I'm saying.
SPEAKER_2: He discovered it.
SPEAKER_1: Let me tell you some advice here, okay?
SPEAKER_1: I once got a phone call that said we'd like to name an asteroid after you.
SPEAKER_1: My next question was, is it headed towards Earth?
SPEAKER_1: You don't want asteroid Tyson to take out civilization.
SPEAKER_1: So they said, although it's safe in the asteroid belt.
SPEAKER_1: So I said, thank you.
SPEAKER_1: So to have a disease that is especially lethal with your name on it doesn't sound like an honor.
SPEAKER_2: Unless Dr.
SPEAKER_2: Tyson was going to also help steer the asteroid away from Earth.
SPEAKER_2: Which is what Dr.
SPEAKER_2: Dannon did.
SPEAKER_3: That sounds like the volunteer firefighter who started the fight.
SPEAKER_3: That's right.
SPEAKER_2: Dr.
SPEAKER_2: Dannon is a wonderful person.
SPEAKER_2: He discovered the disease, but he also helped us uncover the solution for it.
SPEAKER_1: Okay, so now you're using viruses for this, because they're kind of badass at what they do, right?
SPEAKER_1: And so you're recognizing this fact.
SPEAKER_1: So how do you know which virus to use of the countless ones that we share this planet?
SPEAKER_2: Yeah, that's been a journey of probably three decades of earlier discovery before we got to this place.
SPEAKER_2: We use two types of viruses.
SPEAKER_2: One is a lentivirus, which is a modified HIV virus.
SPEAKER_2: 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.
SPEAKER_2: So still infect cells.
SPEAKER_2: And that's good for bone marrow diseases, hematology conditions.
SPEAKER_2: Sickle cell is actually one of them, a hematology disease, where something like lentivirus would be good.
SPEAKER_2: And another virus we use is called AAV, adeno-associated virus.
SPEAKER_2: And AAV is non-infectious, but also can infect cells pretty robustly.
SPEAKER_2: And we use that for our cardiac diseases, as well as other companies have worked on CNS and liver and other diseases using AAV.
SPEAKER_2: So you select the virus based on the target organ, again, where it would be most tropic for.
SPEAKER_1: So you're turning, reminds me of a quote from Abraham Lincoln.
SPEAKER_1: And he said, can we not defeat our enemies by making them our friends?
SPEAKER_2: For enemies?
SPEAKER_1: Well, no, no, that's different.
SPEAKER_3: That was real housewives.
SPEAKER_1: No, the point is, you have viruses, and none of us thinks nice things about viruses.
SPEAKER_1: You turn them into something that can help us, and then viruses become our friends.
SPEAKER_2: 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.
SPEAKER_4: Hello, I'm Finkie Baroque Allen, and I support StarTalk on Patreon.
SPEAKER_4: This is StarTalk with Neil deGrasse Tyson.
SPEAKER_1: So you've said Vector at least 30 times in this conversation.
SPEAKER_1: 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.
SPEAKER_1: And so can a virus otherwise just bust in to do its work?
SPEAKER_1: Or does it need some kind of back door or some kind of trap door that it knows about?
SPEAKER_3: A docking station.
SPEAKER_1: A docking station, how does that work?
SPEAKER_2: I'm glad you say that.
SPEAKER_2: 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.
SPEAKER_2: But taking maybe the cartoon.
SPEAKER_1: Oh, so you're saying in tropism, it's not even biochemical, it's physical.
SPEAKER_2: Yes, yes.
SPEAKER_1: That's what you mean by tropism.
SPEAKER_1: The shapes match up and then there you go.
SPEAKER_2: Exactly, exactly.
SPEAKER_2: So it's like a dock, right?
SPEAKER_2: So think of a vector like a rocket.
SPEAKER_1: There comes the rocket.
SPEAKER_1: You knew that was coming.
SPEAKER_3: Listen, I wouldn't have it any other way.
SPEAKER_2: You're not surprised.
SPEAKER_2: The rocket, the vector is like a rocket.
SPEAKER_2: The gene that you're correcting is basically the cargo, the payload, or even the people, right?
SPEAKER_2: And you're basically, you can use that analogy to think about gene therapy, right?
SPEAKER_2: Taking corrected gene into cells just like a rocket takes people to wherever they want to go.
SPEAKER_2: Where do you want to go, by the way?
SPEAKER_1: I like Earth.
SPEAKER_2: You're fine, okay.
SPEAKER_1: Okay, so a rocket is vectored, right?
SPEAKER_1: It has a direction and it has a purpose and a mission and the velocity.
SPEAKER_1: Okay, so...
SPEAKER_2: I was debating with some of my team about velocity as a value because we want to move fast, but they're like, well, a rocket already has velocity, so it's sort of redundant.
SPEAKER_2: I said fine.
SPEAKER_1: Velocity can equal zero, just to be clear.
SPEAKER_2: Good point.
SPEAKER_1: V equals zero.
SPEAKER_2: V equals zero, right.
SPEAKER_1: Velocity can even be negative as a vector.
SPEAKER_2: I stand down.
SPEAKER_1: Alright, so...
SPEAKER_1: Here's a big economic question.
SPEAKER_1: 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...
SPEAKER_3: No critical math.
SPEAKER_1: Unless you charge like $100 million per dose, which is just absurd.
SPEAKER_3: And then you got to hope that Jeff Bezos is the one who has the disease.
SPEAKER_2: Just write that check right there.
SPEAKER_1: So tell me, what is your relationship to this world of rare diseases and how does that make economic sense?
SPEAKER_2: So I think someone who pursues rare disease is a rare individual.
SPEAKER_2: It takes a certain mission, passion-driven focus, science focus, and entrepreneurship to really go into rare disease.
SPEAKER_2: Bigger companies tend to shy away from rare disease because, to your point, it doesn't make business sense.
SPEAKER_2: But for a small company that's starting out, it makes total business sense.
SPEAKER_1: You were publicly traded, but you'd still be counted as a small company.
SPEAKER_2: 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 patience and we are connected very personally.
SPEAKER_2: So even if we blossom into a much bigger company, we'll always be a startup in our mindset.
SPEAKER_1: Keep telling yourself that.
SPEAKER_2: There's 283 people here.
SPEAKER_2: I think we all feel that way.
SPEAKER_1: 28, 000 people.
SPEAKER_2: Exactly.
SPEAKER_1: 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.
SPEAKER_1: They're not squashed by legacy of whatever people think should be true.
SPEAKER_3: Latitude to be creative.
SPEAKER_1: All of that.
SPEAKER_1: We're loving that.
SPEAKER_1: So, all right, I looked at some numbers before I got here.
SPEAKER_1: I did a little bit of homework.
SPEAKER_1: And there's a website that is all about rare diseases.
SPEAKER_1: What is it?
SPEAKER_1: The National NORD.
SPEAKER_1: NORD.
SPEAKER_1: See, everybody here knows NORD.
SPEAKER_1: 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.
SPEAKER_1: In other words, rare diseases are not rare.
SPEAKER_3: As an aggregate.
SPEAKER_1: In the aggregate.
SPEAKER_3: Is that?
SPEAKER_2: It's funny you say that.
SPEAKER_2: Each rare disease is rare, but rare disease is not rare.
SPEAKER_1: As a category.
SPEAKER_2: As a category.
SPEAKER_2: That's exactly right.
SPEAKER_1: If you bust in and you're good at rare diseases, 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.
SPEAKER_2: Yeah, so actually in...
SPEAKER_1: I shouldn't have said it that way, that's so crass.
SPEAKER_2: No, no, it's great.
SPEAKER_3: This is America.
SPEAKER_2: Corner the market.
SPEAKER_3: We are totally fine with what you just said.
SPEAKER_3: We know exactly what she said.
SPEAKER_1: No, corner the market is so crass, but okay.
SPEAKER_2: The reality is that developing these therapies does take a lot of money and requires investment, and it requires dedicated investors who are here long term.
SPEAKER_2: Also, the government has a program called Pediatric Review Voucher Program that will reward companies who just get an approval for a rare disease, so it sort of helps offset some of those costs, so that there's a nice partnership there between industry and regulators.
SPEAKER_1: You would expect at some level the government to step in if something is not otherwise financial, if it cares about its own citizens.
SPEAKER_3: And are there residual or tertiary kind of benefits that come out of the specificity?
SPEAKER_3: When you solve, it's very specific, can you then say, oh, all these other areas are now helped?
SPEAKER_2: Absolutely.
SPEAKER_2: So we here at Rocket…
SPEAKER_1: What you're trying to say is, can one thing help other things?
SPEAKER_1: Is that what you're trying to say?
SPEAKER_3: Can one thing help other things?
SPEAKER_2: Another way to say it is we have a platform approach.
SPEAKER_2: So once you figure out one solution for a cardiac disease, it's easier to apply other therapies to other cardiac diseases.
SPEAKER_2: We recognize that.
SPEAKER_2: So does the FDA, by the way.
SPEAKER_2: They're trying to make things easier for us through both clinical and manufacturing sort of streamlining.
SPEAKER_3: And when you discover that help in the other areas, do you get a cut of that as well?
SPEAKER_1: Well, if it's patented, right?
SPEAKER_2: Yeah, I mean, we have some folks here who know quite a bit about FTO, freedom to operate, and patents.
SPEAKER_2: But I think that the profitability here takes a long time as a startup.
SPEAKER_2: Some of the most successful companies are only profitable about eight years after their biggest launch.
SPEAKER_2: So that's going to take time.
SPEAKER_2: But we're really here for the passion, the mission, and ultimately the money will follow the science.
SPEAKER_1: So right now, are you tracking certain, do you have certain specialty diseases you're targeting?
SPEAKER_1: What are they?
SPEAKER_2: So we have six diseases that we target.
SPEAKER_2: Three of them are bone marrow derived, which are fanconia anemia, a disease of DNA repair.
SPEAKER_2: The DNA actually can't repair itself.
SPEAKER_2: Carl Sagan and you had an episode with this DNA repair mechanism.
SPEAKER_2: Right?
SPEAKER_2: So this is faulty in fanconia anemia.
SPEAKER_2: I remember that from when I was eight and then again when I was a little bit older and watching your Cosmos.
SPEAKER_2: So fanconia...
SPEAKER_2: You had a pretty good graphic on that.
SPEAKER_2: You did, yeah.
SPEAKER_1: That's right.
SPEAKER_2: Better than, should I say better than the original?
SPEAKER_2: That was a long time ago.
SPEAKER_1: Yeah, yeah.
SPEAKER_1: The original was 1980.
SPEAKER_3: Let's hope, let's hope.
SPEAKER_1: Yeah, you know, 44 years ago.
SPEAKER_1: Just a quick point, I should have just slipped this in there.
SPEAKER_1: What I did know about…
SPEAKER_1: I took biology as a senior in high school, which is inverted from what's typical at the time, I think even today.
SPEAKER_1: I took physics first, then chemistry and then biology.
SPEAKER_1: So biology for me was more, I'll do it because I have to, right?
SPEAKER_1: But there's some things I remembered that the DNA molecule is actually handed.
SPEAKER_1: So if you put a DNA molecule in a mirror, those are not the same molecules.
SPEAKER_1: So, because it turns the other way.
SPEAKER_1: And so one of the early versions, because the artists were, the computer graphic folks were creating the DNA molecule, and it was spinning the wrong way.
SPEAKER_1: I said, no, that's not on this planet.
SPEAKER_3: Oh, wow.
SPEAKER_1: Yeah, yeah.
SPEAKER_1: Yeah, yeah, so the DNA molecule spins sort of helically clockwise if you're looking up from below.
SPEAKER_1: And it'll do that no matter how you orient it.
SPEAKER_1: So, I'm just proud of myself for that.
SPEAKER_3: Yeah.
SPEAKER_1: A little applause for that, I think, but thank you.
SPEAKER_2: That's great.
SPEAKER_1: That's my little thing.
SPEAKER_1: I like chirality and handedness and things like that.
SPEAKER_1: But back to the point.
SPEAKER_1: So you were listing your disease.
SPEAKER_2: Yes, the sticks.
SPEAKER_2: Yeah, so fanconemia is exactly, one of those molecules doesn't work in fanconemia.
SPEAKER_2: One of those repair pathways doesn't work.
SPEAKER_2: So these patients develop bone marrow failure and leukemia in their single-digit years in their teens.
SPEAKER_2: So we have a therapy in fanconemia that is going to be submitted to the FDA for approval first half in 2024.
SPEAKER_2: Just quickly, LAD1 is a disease of, infectious disease, that really kills little boys and girls by the age of two and two-thirds of cases.
SPEAKER_2: So it redefines the word devastating.
SPEAKER_2: They're in and out of hospitals with fungal pneumonias.
SPEAKER_2: And we've now treated nine patients.
SPEAKER_2: All of them are out about two years or more.
SPEAKER_2: And instead of living till the age of two, they may turn 92.
SPEAKER_2: 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?
SPEAKER_2: At the DNA level, correcting the DNA is the most fundamental way that we can cure disease as human beings, as we see it, right?
SPEAKER_2: Third one is called pyruvate kinase deficiency.
SPEAKER_2: It's like a hemolytic anemia, like a sickle cell, or like a beta thalassemia.
SPEAKER_2: Then we have three cardiac programs that our company is the first one to get into that space.
SPEAKER_2: Dannon 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.
SPEAKER_2: Sometimes you hear about these athletes who suddenly fall over.
SPEAKER_2: Now we know why some of them fall over.
SPEAKER_2: They have something like Dannon disease, or PKP2 is another arrhythmia, or BAC3.
SPEAKER_2: 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.
SPEAKER_2: We're trying to go after them one by one genetically.
SPEAKER_1: And you're targeting childhood diseases.
SPEAKER_1: That's the greatest loss of life, is the death of a child.
SPEAKER_1: In the statistics of population.
SPEAKER_3: That's right.
SPEAKER_1: I mean, you die at 80 because, okay, you lost 10 years tops.
SPEAKER_3: And can any of these applications have relevance in chronic lifestyle diseases, which is what we see most of in America?
SPEAKER_2: Yes, there are some folks working on preventing coronary artery disease through a similar gene pathway.
SPEAKER_2: Where people are working on Alzheimer's, Huntington and Parkinson are already targets.
SPEAKER_2: So the way we see it is that we want to crack open the door based on single gene defects, right?
SPEAKER_2: Like the ones I mentioned are like sickle cell.
SPEAKER_2: And that will ultimately...
SPEAKER_1: They're tractable, right?
SPEAKER_2: They're tractable, yes.
SPEAKER_1: Because if there's something that has 32 genes going on, you're in a...
SPEAKER_1: you can't.
SPEAKER_2: Right.
SPEAKER_2: 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.
SPEAKER_2: And I think we're just trying to get the process...
SPEAKER_1: But how ways away is it if we have AI plus quantum computing?
SPEAKER_1: That could be next...
SPEAKER_3: It won't make a difference because it will kill us all.
SPEAKER_2: 2001.
SPEAKER_3: Exactly.
SPEAKER_1: Oh, you say the AI will use the quantum computing to be especially effective.
SPEAKER_3: There you go.
SPEAKER_1: Okay, okay, I take it back.
SPEAKER_1: I take back the question then.
SPEAKER_1: Chuck is right.
SPEAKER_2: I hope in our lifetime, but certainly in some of our children's lifetime, I think we'll see a lot of progress.
SPEAKER_1: All right, 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.
SPEAKER_1: Now in your cases, it's kind of, the morality of it is trivial.
SPEAKER_1: The kids are gonna die, okay?
SPEAKER_1: But there are many genetic disorders, we call them, where you can still live a full life.
SPEAKER_1: It's just, you don't match up with the model human who you compare, you're all your senses and all your limbs, and are they all to match the model human?
SPEAKER_1: Well, then you're normal, all right?
SPEAKER_1: And if you don't match it, then you're not normal.
SPEAKER_3: Like baldness.
SPEAKER_1: So where does, who says what's normal and what's not?
SPEAKER_2: I mean, I think that...
SPEAKER_1: Before 1987, I read that the American Psychiatric Association had, until then, had classified homosexuality as a brain disorder.
SPEAKER_1: 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?
SPEAKER_2: Yeah.
SPEAKER_2: Well, I think what's normal is probably defined by the times and by the culture.
SPEAKER_1: Should it be?
SPEAKER_2: Maybe, maybe not.
SPEAKER_2: But I can tell you what's not normal is...
SPEAKER_1: Because I know 170 years ago what was considered normal in the United States in the South, OK?
SPEAKER_2: And 170 years from now, it might be that much different.
SPEAKER_2: But I know what's not normal, right, which is having these devastating diseases.
SPEAKER_2: I don't think that's normal.
SPEAKER_2: Death.
SPEAKER_2: Death, I guess, is normal, but...
SPEAKER_3: Well, no.
SPEAKER_3: Yes.
SPEAKER_2: But not at a young age.
SPEAKER_3: Not at two years old.
SPEAKER_2: We can all agree that's not normal.
SPEAKER_2: 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.
SPEAKER_2: But I think we start where we start and then see where it goes.
SPEAKER_1: No, because I say that, and I didn't come up with this.
SPEAKER_1: I mean, I see it rising up around me.
SPEAKER_1: What's the film...
SPEAKER_3: Gattaca.
SPEAKER_1: No, no, I know Gattaca.
SPEAKER_1: No, no, it's the film that had...
SPEAKER_1: It was a rock musician who went deaf.
SPEAKER_1: The Sound of Metal.
SPEAKER_3: Sound of Metal.
SPEAKER_1: In that, it's a rock performer, and he plays loud rock music, and then he goes deaf, pretty catastrophically.
SPEAKER_1: And then he learns that there's a whole community of deaf people.
SPEAKER_1: I'm summarizing here.
SPEAKER_1: But then they find a way that they could put devices in and restore some of the hearing.
SPEAKER_1: But he had gotten so accustomed to the silence and the community of others who embrace that state of existence that, no, he ultimately rejected it.
SPEAKER_1: Again, that's a case where he's otherwise healthy.
SPEAKER_1: One of his senses is gone.
SPEAKER_1: And so I wonder where the future of this goes and what kind of future, you know, is there a sort of morality committee?
SPEAKER_1: Is there a, in your field?
SPEAKER_1: Surely there's something going on in the genetics.
SPEAKER_3: 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.
SPEAKER_1: Oh, right.
SPEAKER_1: We would have cured all the diseases.
SPEAKER_3: That all the disease would never, 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?
SPEAKER_1: And just in one other example, Oliver Sacks was a guest on one of our earliest episodes of StarTalk.
SPEAKER_1: I got to befriend him briefly.
SPEAKER_1: We weren't beer drinking buddies, but he's a neuroscientist, bestselling author.
SPEAKER_1: The movie Awakenings was based on his research.
SPEAKER_1: It had Robin Williams in it that brilliantly acted in that role.
SPEAKER_1: I attended a lecture he gave on, I think it was hallucinogenics or something.
SPEAKER_1: He's a brain guy.
SPEAKER_1: But he reminded us of his neurological condition.
SPEAKER_1: So he has, I forgot the full word, but the regular people word, he has face blindness, okay, where you don't recognize people's faces even if you know them well.
SPEAKER_1: 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?
SPEAKER_1: 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?
SPEAKER_1: And he said, no, he wouldn't, because that very affliction in his mind is what got him interested in neuroscience to begin with.
SPEAKER_1: And so I think to myself, again, if we're going to compare ourselves to some like model 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.
SPEAKER_2: 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.
SPEAKER_2: You know, and they were challenged, they were troubled.
SPEAKER_1: Vincent Van Gogh among them?
SPEAKER_2: Van Gogh, Mozart.
SPEAKER_1: Not that it's a prerequisite, but it doesn't preclude that you can be highly creative and productive.
SPEAKER_2: Correct.
SPEAKER_3: I think that that is an outworking of being challenged in a way.
SPEAKER_3: Yes, yes.
SPEAKER_1: Because if you're normal and you're not challenged, then what do you have to overcome?
SPEAKER_3: Exactly.
SPEAKER_1: Right.
SPEAKER_3: I mean, you can say the same thing about poverty, but does that mean that you don't want to end poverty?
SPEAKER_3: 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.
SPEAKER_3: And I say to them, that's not necessarily the case.
SPEAKER_3: There could have been some other stimulus that would have sparked in you whatever motivated you to become what you are.
SPEAKER_3: So it's not, it's what we know that made us.
SPEAKER_3: It's what we know.
SPEAKER_3: So we say it because that's what we know.
SPEAKER_3: But we don't know what could have caused it.
SPEAKER_1: So is the FDA your friend or your enemy?
SPEAKER_3: Oh, wow.
SPEAKER_3: Turn off the camera.
SPEAKER_3: I thought this was a friendly discussion.
SPEAKER_2: Absolutely.
SPEAKER_1: Let me ask it a different way.
SPEAKER_1: Is the FDA more stringent about their tests than most, if not all, other countries?
SPEAKER_1: And is that a good thing?
SPEAKER_2: I think they are.
SPEAKER_2: And I think that's a good thing.
SPEAKER_2: Especially as a scientist.
SPEAKER_1: The results have to work.
SPEAKER_1: They've got to be statistically right.
SPEAKER_1: Especially given how susceptible we are to thinking something that's true that isn't.
SPEAKER_1: Or thinking that something isn't true that is.
SPEAKER_1: That is rampant.
SPEAKER_3: Optimism bias, yeah.
SPEAKER_1: What's it called?
SPEAKER_3: Confirmation bias.
SPEAKER_3: But there is an optimism bias as well.
SPEAKER_1: In testing, yes.
SPEAKER_1: Okay, so given that, how does one get access?
SPEAKER_1: I mean, there's a price.
SPEAKER_1: You're a publicly traded company, so all your stuff is going to cost money.
SPEAKER_1: And I can't afford it, and I have a kid who's dying, so what do I do?
SPEAKER_3: Don't take this personally.
SPEAKER_2: So the question, another way to think about the question is, what is the cost of not giving a life-saving therapy?
SPEAKER_2: And what is the cost to that individual, that family, and to society?
SPEAKER_2: And regulators and payers can come up with a price that makes sense that's based on the magnitude of clinical benefit.
SPEAKER_2: Those are discussions that were...
SPEAKER_2: Insurance companies, payers, exactly.
SPEAKER_2: So insurance companies would ultimately agree to be payers for that therapy because of the data they see.
SPEAKER_2: And that's discussions that we're starting to have now.
SPEAKER_2: And to answer the FDA question, they're absolutely friends.
SPEAKER_2: When we go to FDA meetings, sometimes you can't figure out who's from the company and who's from the FDA.
SPEAKER_2: They're helping us, we're helping them.
SPEAKER_1: They're not on the other side of some wall.
SPEAKER_1: They're a participant in finding the solution.
SPEAKER_2: And they're people, also they have children.
SPEAKER_2: And I think once you understand that this is...
SPEAKER_2: We're learning together.
SPEAKER_2: It opens up the doors.
SPEAKER_2: And again, going back to curiosity and wonder, I think we go into the room with a sense of wanting to learn.
SPEAKER_2: And the outcome has always been great.
SPEAKER_1: So, this is only a question I can ask of a CEO.
SPEAKER_1: How do you measure your risk factors?
SPEAKER_1: Because in space launches, Elon Musk has been very public about his launches where they blow up on the launch pad, right?
SPEAKER_1: And I spent a fair amount of time working with NASA.
SPEAKER_1: I was on their board for a while.
SPEAKER_1: 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 some of them would withdraw the funding.
SPEAKER_1: And my reply to that was, as an educator, you need to teach people that the day you stop making mistakes is the evidence you're not on the frontier.
SPEAKER_1: And so the public needs to be sensitized to what risk means here.
SPEAKER_1: Risk doesn't mean never anything going wrong.
SPEAKER_1: Risk means sometimes stuff goes wrong.
SPEAKER_1: And then provided you learn from that, that's all a good thing.
SPEAKER_1: So how do you, in terms of R&D, because you don't even have a product yet, you said, right?
SPEAKER_1: Okay, so there's R&D versus profit versus all of this.
SPEAKER_1: And how risk averse are you?
SPEAKER_2: Yeah, we need, I think the secret sauce here is the right people, world-class people who are going to believe and stay and persevere with grit and tenacity over time.
SPEAKER_3: Way to suck up to your employees.
SPEAKER_1: Chuck, we are their guests here, okay?
SPEAKER_3: I'll behave, I'll behave.
SPEAKER_2: We need patient investors who believe in the story.
SPEAKER_2: And yes, mistakes are a part of this.
SPEAKER_2: 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.
SPEAKER_2: And the best masters...
SPEAKER_2: I sing Indian classical music, and I play this instrument called the harmonium.
SPEAKER_2: Oh, interesting, okay.
SPEAKER_2: But the greatest masters are the least judgmental.
SPEAKER_2: That's what I've learned.
SPEAKER_2: And even when you play a wrong note, they'll consider it musical, because they hear what no one else hears.
SPEAKER_2: And I think that's the same with making mistakes in science.
SPEAKER_2: There's no right or wrong.
SPEAKER_2: You have to make mistakes.
SPEAKER_2: And I actually applaud SpaceX's being open about it and not fearful about it.
SPEAKER_3: Yes, I do too, because I am not buying a ticket.
SPEAKER_1: I told Elon, I said, I'll ride one of your rockets after you fly your mother on one of them back safely.
SPEAKER_1: I hope you enjoyed my conversation with Gaurav Shah, the co-founder and CEO of Rocket Pharma, giving us a glimpse into the future of gene therapy.
SPEAKER_1: This has been StarTalk, and I've been your host, Neil deGrasse Tysonand.
SPEAKER_1: As always, keep looking up.