"The Tiny Molecules That Keep us Alive"--Dr. T.J. Ha, Boston Children's Hospital and Harvard University

There are millions of tiny machines at work in our bodies, keeping our genes repaired when they break.  These machines--protein molecules--can be watched and monitored by science, thanks to imaging technology developed by Dr. T.J. Ha, who immigrated to the United States from South Korea in the 1990's. His research aims at understanding how exactly these proteins do their work and what happens when they break down, leading to diseases like cancer.  This could have enormous implications for treating childhood leukemia.  Telluride Science featured Dr. Ha in a talk at the Mountain Village Conference Center and the session was moderated by veteran broadcast journalists Judy Muller and George Lewis.

Transcript

Science Straight Up

Season 7, Episode 7

“The Tiny Machines That Keep us Alive”

Dr. T.J. Ha, Boston Children’s Hospital and Harvard University

Moderators: Judy Muller and George Lewis

August 4, 2026

(THEME MUSIC UP AND UNDER)

JUDY: From Telluride Science, this is “Science Straight Up.” I’m Judy Muller

GEORGE: And I’m George Lewis…on this week’s edition….

TJ HA: (04:32) I'm going to tell you stories about machines in your body, tiny machines.//Millions of them in every cell of your body.

JUDY: Dr T.J. Ha is with Boston Children’s Hospital and Harvard University and his work could someday lead to new treatments for diseases like childhood leukemia.

GEORGE: He was one of the participants in this year’s workshops put on by Telluride Science and he explained his cutting-edge research in a talk before a local audience at the Telluride Mountain Village Conference Center.  Judy and I moderated.

JUDY: Our speaker this evening, Dr. T.J. Ha, has titled his talk "As You Can See: The Tiny Machines That Keep Us Alive, Watching Life at Work, One Molecule at a Time, or, as our talented summer intern Caroline Simmons put it, "Eavesdropping on molecular conversations. So she had me at eavesdropping.

GEORGE: Dr. Ha will explain how physicists turned biologists like himself, and they are a rare breed, are using light-based tools to watch how proteins move. In case you didn't know, our bodies depend on more than 200,000 proteins, each with its own task, and because of their tiny size, they're really tough to monitor. It's akin to using a telescope on the moon to film a single person on Earth.

JUDY: But now, new advances in single-model fluorescence imaging have made that possible. Dr. Ha is a leader in that fascinating field, he directs the program in cellular and molecular medicine at Boston Children's Hospital, among many other titles. He studies proteins involved in cancer genes, HIV, and childhood diseases like leukemia. Please welcome Dr. T.J. Ha, (APPLAUSE)

TJ HA: Thanks for the introduction. I'm going to tell you stories about machines in your body, tiny machines. Millions of them in every cell of your body. So, I've been spending 30 years of my life to watch them doing their job.

GEORGE:  Those little machines are proteins and to watch them do their job, Dr. Ha invented some powerful imaging tools. Coating protein molecules with special fluorescent dyes, hitting them with laser beams to make the dyes glow and then tracking their movements. It was all originally designed to study electronic micro-circuits on computer chips.

TJ HA: I actually built an instrument, a microscope, to study materials, and it failed. And then I pivoted. I realized that we can use that same microscope to look at biological molecules one one at a time.

JUDY: And so, Dr. Ha, trained as a physicist, began studying biology and peering into the fascinating world of those hard-working proteins. And he discovered that some of those proteins function as repair crews, fixing the DNA in our bodies when it gets damaged and broken.

TJ HA: So one very deadly damage that DNA receives is called DNA break or double-stranded break, where both strands of DNA are broken at the same time, and that's really serious and happens about 50 times a day per cell in your body.

GEORGE:  But, since our bodies have about 100 billion cells, he noted, the DNA damage is dispersed. And those little proteins are on the job, trying to fix things.

TJ HA: DNA damage can lead to aging, cancer, and many genetic disorders. And we survive to adulthood not because DNA is never damaged, but because they get repaired really, really well. There are many protein machines that can survive the genome to find, detect the damage and repair rapidly and accurately.

JUDY: But over time, the damage to our genes mounts up as we age. And all too often, that can trigger diseases like cancer.  He cited the case of actress Angelina Jolie.

ANGELINA JOLIE MOVIE CLIP: “I have cancer.   I have breast cancer.  Sorry, I’ve never said it out loud.  Kind of makes it real.” 

JUDY: That’s Jolie playing a woman with cancer in the movie “Couture.”  In real life, she’s never had breast cancer, but discovered that she had a mutant gene called B-R-C-A one, BRCA one. That, plus the fact that Jolie’s mother died from breast cancer, meant she had extremely high odds of developing the disease.

TJ HA: Her doctor estimated that she has 87% chance of getting breast cancer. So she had no cancer, but in 2013 she had surgery anyway.

GEORGE: Jolie underwent a double mastectomy as a drastic way of beating those odds. Now, science is looking for ways to correct the genetic errors that can lead to cancer, including BRCA mutations, without the need for preventative surgery.

TJ HA: If you have a defective gene, then you can use a template to to make the correction to correct functional copy of the gene.

JUDY: At Boston Children’s Hospital, Dr Ha and his team are pursuing ways of stopping diseases such as childhood leukemia, using genetic editing techniques like CRISPR. But he concedes there’s a lot of work to be done in the search for effective treatments.

TJ HA: There are many, many different ways of repairing the DNA. We still do not know how to predict the outcome and how to control the outcome. So that's the big gap in our knowledge. 

GEORGE: What they want to know is how does the genetic repair process work? To do that, they cut strands of DNA using CRISPR editing but time the cutting so that they can observe how all those little helper proteins are doing their job.

TJ HA: We have a lock, chemical lock that prevents the final closure, and then in a cell we shine light to actually remove the lock, and then the scissors will close and cut in the DNA within seconds of shining light. 

We can study one molecule at a time, one nanometer at a time because they are very small, and one flash at a time. And for example, my students are busy tweaking the microscope and watching repair machineries at work.

JUDY: My first question: You used Angelina Jolie as an example, which I think is great. And she did something preventative because she knew she had the BRCA gene. I'll call it that, B R C A gene, which dramatically raises your risk of breast and ovarian cancer. And I know other people who have done this preventively, having these organs removed. Where are you now in terms of isolating the BRCA gene and sending a mutation that would? What would it do? I mean, how would that work? And are you close? 

TJ HA: No, we are not close to that. Yeah, I think that there are many technical issues, and one major issue is that it's difficult to deliver this CRISPR medicine to the tissue of interest.

JUDY: He went on to point out that liver cancer is easier to treat with these new techniques than breast or ovarian cancer because medicines injected into the bloodstream pass through the liver. As we continued, George wanted to know more about Dr. Ha’s imaging technology.

GEORGE: I'm kind of interested in how stuff works, and and I think about a conventional microscope which uses glass lenses, or an electron microscope which uses beams of electrons to see very small objects. How does yours work? 

TJ HA: We use actually glass-based light-based microscope, so we use light photons and usually visible light, actually green and red and yellow colors, and the principle didn't really change all that much. I guess in the last couple of years for the microscopy, however, the way we can actually do this now reliably is because of improvement in technologies. The cameras became much much better.

And now we have wonderful tools to attach fluorescent text to the proteins of interest in a very specific manner, and so those are chemistry advances that we have also adapted for our research. 

JUDY: So this fluorescence allows you to see a single molecule move. 

TJ HA: Yes.

JUDY: And can you describe what that felt like when you first saw it? 

TJ HA: I knew that I'm the first one to measure this because they're so new, and whatever I discover, I knew that I'm the first one actually in the human history to to know this. So it was really exciting time back then, although not anymore. You know, I I I just I I just talking. Yeah. 

JUDY: Yeah. But that must have been a moment. 

TJ HA: Yeah. Yeah. 

JUDY: Wow. 

GEORGE: How can you explain in a little bit more depth of how this field of molecular imaging impacts efforts to repair mutations in genes that can cause childhood illnesses like leukemia? What exactly are you trying to do there? 

TJ HA:  One thing that actually we are trying to work after we move to the Children's Hospital is to use our sensitive detection tools because we can detect even single protein molecules. We want to use it to obtain information from blood samples. Usually, there are standard tools that we run to diagnose the disease, but I think there is a lot more information you can gather from from those samples using our microscopes.

JUDY: Can you walk us through one specific disease where this research might make a difference in, say, in kids' health in 10 to 20 years?

TJ HA: I haven't actually thought about a specific disease, but if you actually ask me, give me a disease, maybe I can tell you…

JUDY: I was thinking of childhood cancer, leukemia. I have a friend who lost her 10-year-old to this disease, and they tried everything that was around, and to no avail. 

TJ HA: Yeah, so that I think that so for for leukemia, I mean, there is also a lot clearer route for cure. I mean, for treatment because the the blood stem cells for blood, you know, white blood cell directly. They are, they are, they can be all extracted from your body, from your bone marrow, and they can be edited and then you can put them back into into the cell. I don't think people have used it for treatment for of leukemia, but for sickle sickle cell disease. You know, we have a lot of change that causes sIickle cell, and that is the actually the first and the only FDA approved therapy. And this was done using CRISPR, and the editing was done outside the body, and then they put them back, also after so also eliminating all the you know defective stem cells.

JUDY: Wow.

GEORGE: For somebody who's never heard of fluorescence imaging, how would you explain that to the lay audience?

TJ HA: Ah, okay. So that's a good good point. Yeah, I didn't know anything about it. Also, I before I began to do research. The fluorescent molecules are special among the dyes because they they are really good in actually giving you back the light, but just slightly different color. So if you you know shine light, blue light on your fluorescent molecule, it'll give you a green light.

GEORGE: And…as he explained, if you filter out the blue light from the laser and only look for the green light, you can find those individual molecules glowing away.  

JUDY: Dr Ha has had an interesting journey because he was a physisist to begin with, and then got into biology and now he’s at  Children's Hospital in Boston. 

JUDY: What drew you into pediatric medicine research?

TJ HA: So that's that's really interesting question. I'm actually inspired working there, and see kids who come, and and I have two physician scientists working in my lab. They're you know medical fellows and residents, and one one of them joined the lab because he was treating many of the kids who have a condition that is found mainly among kids who went through these bone marrow transplants due to like leukemia and so on, and or and then and this disease is has no known molecular mechanisms, and you just diagnose based on five symptoms, and platelet count is low and and for the symptoms, and he's really upset that he he doesn't really he cannot offer anything better. So he wants to use some of our imaging technologies to study a particular pathway that he think is involved, and yeah, so so in this case, actually, he's not working on DNA repair, but I'm happy to provide space and resources so that he can actually pursue the question.

JUDY: I can imagine that pediatric researchers across the country, are keeping an eye on this. Is there a lot of interest in what what you're doing? 

TJ HA: I hope so. (LAUGHTER)

JUDY: Which leads me to the question, which is it's a difficult time right now for funding, and we're losing scientists to other countries. Do you have that pressure, or are you pretty safe with your research and your…

TJ HA: We, I think, no, no one is immune from this, and we can we can feel and see it every day, and you can imagine that the fire hydrant and budget cut, then you know you don't fix it quickly or fix it with leaks and so on. So I think this is a problem, and it's hard to recruit now people from other countries, China or Europe, and our own people are going to Europe for postdocs, and even people who have trained in the U.S. They are now taking like faculty position in other countries. So it'll it'll it'll it'll be difficult. I think there's a really great impact of having highly concentrated collection of really good people working on similar problems, and I also like the idea of spreading the West evenly across the world. But there's also value in, you know, in creating high high density. 

JUDY: What can we do to keep them here? Lock them in the lab?  (laughter) 

 Money, probably incentives. 

TJ HA: Yeah.

GEORGE: How how difficult it is is it for you to find people to staff your lab who have the combination of skills like yours that range from physics to to medicine to biology. 

TJ HA: Yeah, so I think there's self-selection. So I think some students who who feel that they don't know enough math. 

GEORGE: Self-selection, did you say?

TJ HA: Self-selection, Yeah. So maybe people who think that they that they're not interested in doing math or building instrument, they don't apply. But in terms of picking among those people, I I don't look for particular skills. I. I look for people who can most benefit from training in the lab, training maximizing their training potential, and generally, you know, my my view is that people who are good, they they always find out what they need to do to succeed at this level, and I mean that's the kind of skills that that you're looking for not particular, you know, ways of doing doing things.

GEORGE: When you were growing up, what's what initially sparked your interest in science? What got you headed down that path? 

TJ HA: I think I I was just very curious. Still, hopefully, I'm still curious. It's it's just one. I want to know what happens if I do that, and that's and the same back then, and same same here. And usually, I mean, if I find something funny, right? Then then I have a theory of what's going on, and then I design some things to do to test my idea, and then when it turns out to be correct, and there's no better feeling than that than that. And I mean, I think there was like that was still growing up.

GEORGE: Here’s a fun fact about TJ Ha. After he got to the United States, Dr. Ha noticed that Americans were having trouble pronouncing his Korean given name Taekjip (TECH-jeep). He decided to go by T.J., something inspired by a guy named O.J. and by something he saw on television on June 17, 1994.

(ANNOUNCER) This is a special report from ABC News….

PETER JENNINGS: I’m Peter Jennings at ABC News headquarters…let’s go immediately to a picture in Los Angeles//down there on the ground is a white Ford Bronco//police believe they have located OJ Simpson..wanted on two counts of murder…in this white Bronco going somewhere. ABC’s Judy Muller is with us from Los Angeles. Judy can you tell us where they’re going?

JUDY FROM ABC TAPE: I can’t tell where they’re going except that they’re headed west…

GEORGE: Yep, that’s my wife and podcast partner, Judy, helping Peter Jennings cover the infamous O.J. Simpson Bronco Chase. ABC News won an Emmy for that.

JUDY FROM TAPE: (04:30) This has been one of the most extraordinary news events I’ve ever seen unfold…

GEORGE: So, fast forward to the present day, lDr. TJ Ha was quite surprised when he learned Judy was connected to that extraordinary event that caused him to adopt a new name.

TJ HA: (5:44) I learned today that Judy was the voice on the broadcast. I said, "Wow, this is brilliant! I'm going to call myself TJ. It'll be much easier. That's why I'm TJ.

JUDY: As we always do, we made time for questions from the audience.

QUESTION FROM AUDIENCE: (54:44) Thanks. I was wondering if your lab has been affected at all by controversy surrounding the use of CRISPR and DNA modification. The idea that we shouldn't be messing with that. Where are we going to try to produce? Perfect human beings, that kind of thing, has that impacted you at all? 

TJ HA: Yeah, so that that has not impacted us because we are we are very bad in actually doing exo-gene editing, but I think this is something that we we think think about A lot, and you know there was a CRISPR baby story from China, and clearly that was not something that he should have done.

JUDY: What does that mean, a CRISPR baby from China? 

TJ HA: Yes, I think that was what before the pandemic, maybe 19, sorry, 2018 or so, and scientists actually announced that he, you know, created two two babies whose genome was edited two girls. Yeah, and he he was put into jail for prison for three years, and and yeah, yeah. There's a big, big controversy. 

JUDY: But it could be done?

TJ HA: Yeah, it can be done, If you if you know how to predict the outcome of gene editing, and and that's a big if, and it'll be different for each person because you have different genetic backgrounds, but let's say you know how to do it safely and how to predict the outcome, then should you should you be allowed to do it? I wish my son can dunk, (LAUGHTER)  but I know that that's not possible. But but that's clearly that's not a reason to do gene editing for your descendants, but what about you know you know taller person or better IQ? Where where do you actually draw the line? It's something that I think the society has to think hard about. What do you think?

JUDY: What could go wrong?

GEORGE: Go wrong, go wrong.

WOMAN IN AUDIENCE:I think that there's so much valuable work being done on disease cure. You know, focusing on the ways that humans suffer from damaged DNA, that sort of thing. I would hope that that other controversy wouldn't be an obstacle to progress in in that direction. 

TJ HA: Yeah. For yeah, for example, if you can do embryo editing, but without actually editing the germ line cells, so that you you edit cells that will become your body, but not your you know sperms and eggs. Then it's not going to be heritable. So if that is possible, then I mean ethically it should be much less you know severe. And then in that case, then then still you know. But yeah, in that case, you know, who can afford to do this?

GEORGE: Well, I think that's about all the time…

JUDY: I would like to say thank you for bringing O.J. into this. 

GEORGE: Oh yes. 

JUDY: Never would I have dreamed that he could follow me here. 

GEORGE: It's interesting how the how we all connect, isn't it?

TJ HA: Learning that she worked for ABC// and then she says she did the voice of that newscast. 

JUDY: Saying deep things like ‘he appears to be going off the exit at Sunset.’ (laughter) What do you think that means? Deep.//but thank you..

GEORGE: Thank you so much.

TJ HA: Thank you (applause)

JUDY: Thanks also to our sponsors, Alpine Bank and the Telluride Mountain Village Owners’ Association.

GEORGE: Mark Kozak is the CEO and Executive Director of Telluride Science and Cindy Fusting is CFO and Managing Director.

JUDY: Sarah Friedberg is Lodging and Operations Manager and Annie Carlson is in charge of donor relations.

GEORGE: If you’d like to donate to the cause, go to telluridescience-dot-O-R-G. Please tell your friends that’s where they can find our podcasts or on their podcast apps at “Science Straight Up.”

JUDY: And if you have questions or comments, you can email us… science straight up…all one big long word, science straight up at telluridescience-dot-O-R-G. I’m Judy Muller.

GEORGE: And I’m George Lewis, inviting you to join us next time on Science Straight Up.