Wendy Corr:
Well, hey there folks, welcome to The Roundup. We're a Cowboy State Daily podcast that focuses on interesting people in the Cowboy State.
I have to say, just as a disclaimer, the gentleman we're going to interview today, he doesn't live in the cowboy state, but the work that he did in the Cowboy State has revolutionized - and I am not understating this - has revolutionized medicine, biomedical research, and affects each of us in our everyday lives. So I am so thrilled to be able to introduce Hudson Freeze, Dr Hudson Freeze. Hud Freeze spent some very formative time in Yellowstone National Park here in 1966, and he's got some amazing stories to tell.
But first, I just want to say, Hud, thank you so much for being on the podcast today. You and I have a real interesting, interesting and great, great connection as to how we met, but, but good, good day Hud.
Hudson Freeze:
Wendy, it's so good to be on your program here, and I'm glad that I can be the New Year's Baby.
Wendy Corr:
You are the New Year's Baby. You're ringing in the New Year with us. Fantastic. I have to a little bit of backstory here. So my music partner, my life partner, Dan Miller, Dan and Hud grew up two blocks from each other in the tiny town of Garrett, Indiana, and they then reconnected in California. And they were, they were great friends, and just bummed around Southern California for a while, right?
Hudson Freeze:
That sounds about correct.
Wendy Corr:
While Hud was getting, getting his doctorate and working on all the things that have led him to his career, Dan was being an actor, and he was taking acting lessons, he was working there. So the two of you have this great connection, and I got to meet Hud in person a few years ago.
The work, Hud, that you have done, the work that you have done, has absolutely changed lives and and has ripple effects. So Hud, tell me how you got from Indiana to Yellowstone National Park, for starters, and how that all came about.
Hudson Freeze:
It was a blessing stroke of luck, that's for sure. So I was an undergraduate college student at Indiana University, and I was, you know, one of the students in microbiology, and it's called bacteriology at the time, and you know, I wanted to do some research.
And so my advisor said, “You need to go down and see Dr Brock.” And I had heard Brock give a lecture before, and I talked to him, and he says, Well, we're not working on that stuff right now, but what we're doing is we're going to go to Yellowstone. Would you like to come? You know, it's sort of like we're taking the first trip to Mars. You want to be on the rocket ship?
Wendy Corr:
Absolutely.
Hudson Freeze:
And I thought, My gosh, I've never been out of Indiana except to go, you know, a few miles that way, that way, and I might actually get to see mountains and hot springs. Yeah, I thought, oh, you know what? What could be better? I've not been out of Indiana. Let's give it a whirl.
And the way this got connected, Tom was on a trip to the West Coast, and then he went through Yellowstone and saw all these beautiful colored hot springs. And you knew the temperature was really high boiling water in some cases, but there were all these colored things around there. Well, what? What was that?
He thought it was probably bacteria and algae that were growing in the hot springs. And what was amazing is nobody thought that you could live above 50 degrees centigrade, and that's, you know, about like 130 that's somewhere around there, you know, kind of dishwasher temperature that you could not even go close to that.
And he said, No, it's not true. I think you can live any place there's water, even if it's boiling. And so this was his idea. And he said, come along and we'll see what we can discover.
Wendy Corr:
So that's how you got to Yellowstone. And you get there and you're, you're actually doing the the digging in the water stuff, you're pulling samples and things like that. At what point did you discover that you really you found something that could be revolutionary?
Hudson Freeze:
Oh, gosh, there was none of that. I mean, that's what was really important about basic science. I mean, you do it because it's, well, gosh, that's funny. You shouldn't be able to live. Or, how do you do that? You know? So that curiosity that brings you in to start with.
And so I was an undergraduate student, I was curious, all right, and we weren't sure that you could actually grow this stuff in a laboratory. So it took about a month after I got back to look into trying to make the bacteria that we thought were there, and we could sort of see them, get them to grow in the lab.
So I had a bunch of different experiments going. I picked up a tube that had medium growth medium in it that I added a couple of drops of spring water to, and I would swirl it like that. Nothing in there to see right. Next day, no, next day. No, wait, I'll come back tomorrow.
There’s stuff floating around in there. And this is at 70 degrees centigrade. That is about, oh, I don't know, 160-170 degrees Fahrenheit, very, very hot, real hot.
And so I thought, well, let's take a look and see it's really bacteria. So I take a little pipette, which is a little tube, put it in there, went over the slide, put it in the microscope. Is the honest truth. I still get goosebumps when I think back to that moment. So I'm focusing the microscope. See all these worms crawling around, all these microscopic worms, and I am just thrilled.
But there's no application. There is no need for having this other than, gee, that's funny how they grow. So it turned out that, you know, I published a couple of papers and tried to understand how they survived, but that that was about it, and there was not a big use.
I think at one point, Proctor and Gamble came to us and thought maybe they could add this stuff into Tide, and that it would make clothes cleaner at higher temperatures.
Wendy Corr:
Really, that's all that was? Okay, all right, so, so at what point was the connection made that, wait a minute, this actually, this actually is, is the key to everything.
Hudson Freeze:
So I didn't make that connection. The guy who made the connection is named Kary Mullis, and he was probably on an LSD trip. He's an unusual character. He came up with the idea.
And so what's involved is DNA hangs together as two strands, but if you raise the temperature, you can make them melt apart.
Wendy Corr:
No kidding?
Hudson Freeze:
Yeah. And you lower the temperature, and they come back together. So if you take the temperature up and you provide an enzyme that will actually replicate the DNA, and that have been known for a long time, you can make two identical copies of that, right? And then, you know, if you take the temperature down, and then the, you know, strands come back together, and then they would come apart.
The problem was, if you added this enzyme every time you did this, because the enzyme won't work at high temperatures, where the DNA melts. So every time you wanted to go in and go from two to four to 16 to 32, to 64 every time you do that, you'd have to add more enzyme, more enzyme,
Wendy Corr:
So you're diluting it, right?
Hudson Freeze:
Well, it's not only that, because you inactivate the enzyme each round, so you have to add more, so that you've got the driver for it.
So what happened is, he had this idea that came from, I think maybe somebody else too. He says, Well, what if we use an enzyme from this organism that grows in Yellowstone. It's very happy up at that temperature. You don't have to add it. You add it once, and you forget it, and you take the temperature up and bring it down.
Bringing the temperature down doesn't hurt it. Take it up again. And so you could make one DNA molecule, any kind of DNA molecule, into a billion copies,
Wendy Corr:
A billion - that's monumental, because then the applications for it are everywhere. They're for research, but they're also, for example, I mean, I'm a true crime aficionado, and so you hear about DNA advances in DNA research, and you can't - you know, at one time in the 1970s DNA meant nothing, and you can't find out. If you lose this sample, you're done.
But with this new research. With this new discovery, they're like, oh, so we can replicate this, and now we can solve crimes that happened 30, 40, 50 years ago.
Hudson Freeze:
And that's how many accused criminals who are serving time get off. Because you can show their DNA does not match the DNA from the crime, exactly. It's been a big help.
Wendy Corr:
So, that's just one application - there's so many others, vaccines. Hud, you can research them. You can create vaccines because of this enzyme that was found in Yellowstone. Tell us how that works.
Hudson Freeze:
Well, anytime you have a piece of DNA, it almost doesn't matter, even if, as I said, if you have one copy of DNA, you can convert that into a billion copies, which then allows you to look at the sequence.
Now, get a little bit techy here. The sequence determines what the gene is making. And there are four bases, A, T G and C, A pairs with T, G with C. And so you're able to, when you melt these apart and provide the raw materials, and the polymerase, it knows how to stitch it together and make exact copies, so you can multiply it that way.
So even in the tiniest amount of DNA, you can select a piece and say, okay, and we knew how to find the sequence. We didn't know how to amplify it, but you can pick that and you can see if there is a mutation in that gene, you can tell if there's a variant of some sort that shouldn't be there, and maybe that's responsible for some kids being sick.
Wendy Corr:
Which is where you come in and where you took off and changed the trajectory of your research. Hud, tell us about your research, because the research that you're doing, now that you can amplify and view and study the mutations in genes, you are able then to identify these diseases in children and help them.
Tell us about your work. And your work is at Sanford Burnham Prebys, and that's in California. And tell us about tell us about what you're doing with kids there.
Hudson Freeze:
Well, so I'm a basic scientist. I'm a lab rat. I'm not a physician, but I had, my sister is developmentally disabled. And, you know, I was, and still am very close to her. So, you know, I have a certain affinity for kids that have problems.
And I have been doing some work involving, uh, slime molds, if you can imagine. So I did some work with that, but then one of my friends sent me some cells from a patient who had some, some disorder in these, these things that we study.
We didn't know what it was, and I looked at that, and I said, Well, I think I could make a difference by applying some of my old work to this. So we were able to, in a few cases, actually end up treating some patients with a simple sugar.
I mean, not just any sugar, but a specific sugar that we understood the fundamental basis of in the biochemistry for it, and then we were able to see that the gene that would be important for making that had a mistake in it.
And so that one wasn't good enough to power things through. But if we added, in some cases, not all, if we added a certain sugar to the diet of these patients.
Wendy Corr:
No kidding?
Hudson Freeze:
Yeah, and it was really wonderful. And so, you know, as a basic scientist with no medical training, I was able to get in and have a lot of relationships with physicians and with families. And of course, having the relationships with families was a lot like being at home, right?
I mean, all these kids were around, and you know, I feel very comfortable with that, and then knowing that I might be able to help them, even if it's just for a diagnosis, that's really important to the parents. We never found out what was wrong with my sister and I…
Maybe it doesn't cure it, but it gives you some knowledge that somebody out there knows, besides just the suffering you're doing with your own family.
Wendy Corr:
And of course, one of the things that you have learned and that you've experienced is that even though, right now you can't cure it, the advances that have been made since 1966 at Yellowstone National Park have gone leaps and bounds. And so someday, with this basic research, maybe there can be a cure for these.
Hudson Freeze:
Oh, I think so. In fact, I would say every, every biotech company, every university, every one who does anything in biology is using PCR.
Wendy Corr:
And so PCR is the…?
Hudson Freeze:
Polymerase Chain Reaction. Okay, that this guy, Kary Mullis, developed, you know, coming from - but the critical ingredient was adding the thermus aquaticus. That's what we named this thing, polymerase. So it's called TAQ, T-A-Q.
Wendy Corr:
And I have to say, you've got it there with you. You received a very special award for yourself. You’ve got to hold up. You got to hold it up because it's so cool. So Hud, you received the Golden Goose award. I love that. The Golden Goose award for your work on Thermus Aquaticus.
Hudson Freeze:
And the basis of the award is, here is basic science that people might ridicule. Why are you going to hot springs? And, you know, trudging around and doing things that has no practical application? Come on, what are you doing?
Ah, but you wait a little while, you get the right things together, and now suddenly it changes the world.
Wendy Corr:
And it has changed the world.
Hudson Freeze:
Yeah, it really has.
Wendy Corr:
And so tell us other ways in which this work has changed the world. Because, I mean, we've talked about crime, criminals. We've talked about vaccines, we've talked about childhood diseases. What are some other ways that PCR is being used in science and in practical applications every day?
Hudson Freeze:
Yeah, you know, I think if anybody has ever gone to 23andMe, okay? There, they use PCR to take a little bit of your DNA, amplify it, and then see what your origins might be.
But they also will do some very targeted things, where, if you have a, let's say, a mutation that is in a rare disease, but still it's a very common mutation in that disease, they'll tell you about it.
And the reason that's important is because if you have two people who would have mutations in that same gene, their children might have either a 25 or 50% chance of having a disease that would come from that so prenatally you can decide, well, is this a good match? Should we do in vitro fertilization? If you're oriented that way?
So you can decide based on PCR, and of course, that that then leads into the 23andme, to what is your ancestry? Where did you come from? What was interesting was, my wife had me do this, and there's nothing too surprising in our backgrounds, except they said, you carry this mutation, and it's one of the diseases that I study, but you need to have two of those mutations in order to be sick.
So I had one of them, and I thought, Oh, my God, what if my sister has this disease that I work on. We checked her DNA, and she doesn't have it. But, but again, you know, you realize that sometimes, if you do this, you'll have a little bit of a warning - if you need it. If you don't need it, doesn't matter.
Within the Jewish population, there's a couple of disorders that are very common, and so typically, the Eastern European Jews will have a set of disorders that come along. And, you know, because they're, you know, they stay in small communities and get married to each other, and so, you know, you can have that sort of founder effect of these things.
And you know, at one point over the last five or 10,000 years or something, it may have had an advantage, maybe it prevented you from getting a disease, but the cost of that was that you also had sick kids. But evolution weighs and says, Well, okay, it's worth the risk. We'll keep it around.
Wendy Corr:
So I want to, I want to transition just slightly and segue into speaking of sick kids. You were recently named the distinguished Endowed Chair of the William Roux Foundation, or endowment. And, yeah, and, and this is an amazing story as to how this came about. And this endowment funded your research into these childhood diseases.
But the story, I think, Hud, is just, it's very, very touching. And I again, this is practical application of science that we all on this lay level, don't think about we don't think about all the research that goes into these things, until we have a sick child, until we have a child with a genetic mutation in their blood.
Which I discovered last year with my daughter, who had a major, major health issue last year, and long story, but I found out that I was, I was a carrier for the genetic mutation. I didn't know it until afterwards, but it caused her a year's worth of life threatening illness.
These sorts of things and these sorts of discoveries don't always come at the right time, but when they do come, when these discoveries do come, they can make a difference in the future.
So tell us, tell us about Rocket, because I love this story. This is a fantastic story about Rocket.
Hudson Freeze:
And this is all blessing or luck, or call it what you will. So it was now, right around Christmas, about 18 years ago, we have been sent some cells from the patient, and we had analyzed them, and the dad wrote to me, and he says, “Well, as a Christmas present, you think you could do the analysis and see if this is what we think my child has?”
Well, there's one version of this that's treatable, there's another version of a different gene that's not treatable. And we did the analysis and told him, I said, “Well, it's not the treatable kind.”
“Okay. Well, my mother and I would like to come down and see - the grandmother.” And I said, “Well, I don't have much to offer you, but you're welcome to come down and we'll talk.”
So the grandmother, Dinah Roux, comes down along with her son Taylor, and Taylor says, “Well, is there any treatment?” I said, “No, there isn't.” And Dinah very quickly, elegant, elegant lady says, “Well, what's the biggest obstacle in the field right now?”
So I told her a little bit about what that is in terms of diagnosis. And she said, “Well, Could you, could you do something about that?” “Yeah.” “Well, how much would it cost to get that going?” And I said, “$100,000.”
Okay, okay, okay. “Well, I'll talk to my husband about it, but I think we can manage that.”
So, so that happens, and every year since then, they've given us between $125,000 and $250,000 to carry on our work in the lab on these disorders. And in doing that, they realized, of course, that this should be done in perpetuity.
So they created this Chair. They made a really quite substantial donation to the Institute, and, you know, in my name, and creating this chair, and it says, it even says that - I have trouble, but there's an “honoring Hudson Freeze,” you know, so. And there, there's a chair that has all this engraved on it.
Wendy Corr:
An actual, an actual physical chair. There's a physical chair.
Hud Freeze:
It's not just a figment of your imagination. So, so anyway, What happens is that now the proceeds from that, the interest then goes to my lab, or whoever my successor will be, and they can carry on work in Rocket’s name, in Will's name, and they kind of ensure that he's going to be around for a long time.
And what's been interesting, interesting - and again, you have no way of knowing how this is going to come out. Early on, the family held a fundraiser for us at the old MGM Studios, and it's because the dad is in the business and one of mom's brothers is in the music business. And so we got autographed guitars from Trent Reznor of Nine Inch Nails. We had a coat that Madonna wore. We had autographed books and things like this. And so, you know, we had that kind of a fundraiser.
Wendy Corr:
That's really great.
Hudson Freeze:
But it turned out that mom's side of the family is enormously prolific. Her sister Liberty is a famous model in London who then moved to the US and is now married to Jimmy Ivy, who, with Dr Dre, was Apple Music.
Wendy Corr:
Oh my goodness.
Hudson Freeze:
And so she said one time, she said, “Well, Jimmy wants to throw a birthday party for me. I don't need presents. How about they give it to the Rocket fund? Is that all right?” Yeah, yeah. Good.
And, one of mom's other sibs is named Atticus Ross, and Atticus is Trent Reznor’s creating partner in Nine Inch Nails, and the music for the social network and all these other things. So, so suddenly I fell into this group of people who are not only famous, but they also have an immediate connection to all of this, and you could have never predicted it. And that's not why you do the work.
Wendy Corr:
No, no, it's not, but it is. It enriches your life, amen, and then enriches the lives of the people who you touch. And Hud, you have - the work that you have done and that you've contributed to, and not on your own, but in so many ways, collaborated with people to create these amazing miracles and diagnoses and advance the work of science. Hud, this is, it's just phenomenal. And it all started in Yellowstone National Park.
Hudson Freeze:
Yes, it did.
Wendy Corr:
It's been a blessing to so many then, because of that. Hud, thank you for explaining that in ways that us lay people that are not scientists can understand, and for the work that you're doing.
Is there a place that we can go to find out more information about the work that you're doing and the work that your colleagues and your peers are doing for this, this continuing research?
Hudson Freeze:
You can go to Our institute, which is Sanford Burnham Prebys Medical Discovery Institute. And there is a page there that refers back to our work, and there's information about the Rocket fund. There is also a family group that is very, very active for covering all of these disorders.
Now there, you know, I was involved in the first discovery of one of these things back in about 1980 but there are now 200 of these diseases, 200 of them. And so there is a family group that is trying to at least serve all the families. You can't touch them all, but they're called C D G care.
And CDG stands for congenital disorders of glycosylation, but, but that family group has just been awarded a five year grant from the Chan Zuckerberg Initiative so that they can go out and make the these disorders better known to physicians, to families, to serve as a resource for people to come in and, you know, really benefit from what we know, scientifically and medically.
Wendy Corr:
That's so amazing. What are you working on next, Hud? What's your next project that you're working on?
Hudson Freeze:
Well, we've we've got several, we have about three new diseases that we've discovered working their way through the system to prove that they're really diseases.
And there was another one that we've been working on for a while called Saul Wilson syndrome. And that's a kind of dwarfism, and it's just it's made, if you can believe this, from one change in just one of the genes, not in two, not in both copies, but in one. And we're trying to figure out the basis of that, and we use patient cells to then differentiate them into things that would be given rise to bones, because their bones don't - so maybe you can understand that better.
A bunch of other things that are more basic science. So I keep straddling between the two ways.
Wendy Corr:
You are busy and you are just creating and collaborating and making a difference in so many lives. Hud Freeze, thank you. Thank you so much for being on the show today, for kicking off our new year, and for all the work that you're doing. I have to ask one more question - there was a movie made with Harrison Ford and Brendan Fraser in it, and I want people to know how the movie Extraordinary Measures links to you and to your work.
Hudson Freeze:
Okay, so there's a couple clips out of the movie that I use in some lectures because Harrison Ford had just the right words. So I had worked in about 1980-81 for a guy named Stuart Cornfield who was in Washington University in St Louis, and we were working on how enzymes find their way to the right place in a cell.
And what was involved was called mannose six phosphate. And that is a little thing that you put onto a sugar chain on a protein that directed up this way.
So anyway, I knew the guy that he played, and, you know, there was in the in the same lab as I've been in and, and so actually, I wrote to Ford, and I said, You did a great job of doing this, you know, doing this part, because I know the guy hit it right on the money. I said, “Could we use your picture from that to advertise the scientific meeting.”
And he's and two days later, he answered, and he said, “Yes,” so that was good, but the whole story was quite accurate, and it, the movie, “Extraordinary Measures” gets played in a lot of rare disease settings.
Wendy Corr:
Okay, but the movie, then, it focuses on the same work that you've been doing all of these years.
Hudson Freeze:
Somewhat similar. Yeah, yeah. I mean, there's an overlap in that. And, you know, not all of it is exactly what I'm doing, but, but it's in the same general area, and we use the same kind of approaches, and I use nano six phosphate oftentimes, because it turns out to be an ingredient that's important for me.
Wendy Corr:
I know that that's something that has come up in conversation before. I'm like, I know that this movie has something to do with your research, and so I wanted to, I wanted to check that out and and have people, if they're interested in learning more about this process and they want to hear a story about it, then this is a story about how genetic research and these the genetic work that you're doing, how it impacts people's lives.
Hudson Freeze:
That's right, absolutely.
Wendy Corr:
Hud, this has been so interesting. Thank you for being a part of our The Roundup family now, and also for continuing to do the work that you do. And we hope to see you very soon. So thanks for being a part of this today.
Hudson Freeze:
Wendy, thanks for the privilege and the invitation. Happy New Year.
Wendy Corr:
Happy New Year to you as well, and Happy New Year to all of you. 2025 is going to be a great year, and we're glad to kick it off on The Roundup with Hud Freeze, and this really important work that he's doing. Folks, have a wonderful week. We will see you next week, right here on The Roundup.
