Skip to main content

Hudson Freeze: Golden Goose Winner talks Mold, Movies and More


Hudson Freeze’s path to glycobiology was a slimy one.

Freeze was a graduate student working with microbiologist Thomas Brock when they delved into the hot springs and geysers of Yellowstone National Park in search of microbes that thrived in the high temperatures. One of the micro-organisms they identified, dubbed Thermus aquaticus, produces an enzyme that could withstand the process needed to unravel and copy a strand of DNA.

That enzyme later became the foundation of today’s gene-splicing technology — and led to the pair winning a 2013 Golden Goose Award for groundbreaking, publicly funded research. But that was just the start for Freeze, who’s now one of the leading experts in glycosylation disorders — rare but often deadly illnesses caused when a genetic glitch leaves the body unable to assemble chains of carbohydrate and protein molecules. Scientists have identified dozens of these ailments, which can result in everything from seizures and digestive problems to improper development of the brain or skeleton. Some disorders have been identified in fewer than 10 patients.

His first contact with the field came in graduate school, studying the slime mold Dictyostelium discoideum. The species normally exists as a single-celled organism. But when food gets scarce, “A hundred thousand or so cells join together and form a kind of mobile slug — that’s exactly what it looks like — and it’s covered in slime,” Freeze said. “This now rather coordinated organism can move toward heat and light and eventually, when it finds the right place, make a stalk out of a portion of those cells.”

When the stalk forms, the rest of the organisms form into spores that collect atop that stalk, allowing them to be picked up and carried off to reproduce in a new location. The composition of the slime and the resulting stalk was still largely unknown at the time, so Freeze devoted his thesis to investigating that question. A significant portion of it was formed from carbohydrates, which led him to explore the chemistry behind them. 

That experience led colleagues to ask him for help with their own analyses. And in the process, he found mutations in some slime molds that affected their production of enzymes that helped them digest their food. And around the same time, other researchers were starting to find similar problems in humans — studies that led to the identification of the first glycosylation disorders in the 1980s.

“I then began to get more interested in these diseases and how slime molds could serve as a potential model,” Freeze said. And when he examined cells from patients with one of these still-emerging disorders, he found patients’ bodies had similar defects in assembling sugar chains.

“I had earlier decided that maybe all my slime mold work wasn’t going to amount to much, and maybe what I should do was go off and go to medical school. Maybe I could make a larger contribution that way,” he said.

But the same week he got an acceptance letter to medical school, he also won a grant from the National Institutes of Health to continue his study. He stuck with the lab.

Freeze is now the director of the Human Genetics Program at California’s Sanford-Burnham-Prebys Medical Discovery Institute, which houses the only lab dedicated entirely to congenital glycosylation disorders. He’s a former president of the Society for Glycobiology and the Federation of American Societies of Experimental Biology. In that role, he’s raised concerns about funding for basic research and urged scientists to speak out about their work.

“One of the things I was always trying to push for was people getting out there talking in everyday language to people who don’t understand where science comes from,” he said. “Those people can be our advocates, and I think it’s really important for us to do that.”

He praised NIH Director Francis Collins for his ability to wrangle more funding out of Congress in recent years, but he said years of largely flat funding may have taken a toll on the field and driven off talented researchers.

“I think we’re at a point where there’s support on both sides of the aisle for scientific research, but we have to keep pushing that and now show to people out there, including the political figures, that we’re producing something,” he said. “It’s one thing to write in a journal. It’s another thing to get out there and talk to people about it, and we don’t do enough of that. There is an art to science communication, and it’s becoming more appreciated. We just need more of it.”

Glycobiology got a Hollywood moment in the 2010 film “Extraordinary Measures,” which starred Harrison Ford as a scientist looking for a treatment for one of those obscure disorders. Freeze wasn’t involved with the movie, but he’ll vouch for its scientific accuracy, down to the notations on the blackboards in the background.

And the advances in genetics that flowed from those Yellowstone hot springs have opened new pathways for research into those conditions, allowing scientists to help identify mutations that shed light on different conditions. Genetically derived therapies for those conditions are still “a ways down the road,” he said, but devices like the gene-splicing tool CRISPR now are used regularly to insert snippets of mutated DNA into cells for study.

There’s also a personal aspect to his work. When Freeze and his wife had DNA testing done through a commercial genealogy service, he found he carried a gene most commonly associated with a glycosylation disorder. And since he’s well-known as an expert, he’s occasionally contacted by families dealing with one of these diseases, which are often detected when developmental problems show up in early childhood.

“Because of this less-than-full-blown notoriety of glycosolation, there are children I know who have died from this who could have possibly been saved and certainly had better quality of life if there had been more outreach,” Freeze said. The National Institutes of Health have experts who can help, but scientists need to do a better job of letting physicians know that help is available, he said.  And in the Internet age, he said, researchers have an ally in organized, activist parents, who increasingly reach out online to scientists like Freeze for help.  

 “Activist parents are all over the place now,” he said. “There are a lot of self-help groups and family alliances for these disorders. That’s really encouraging.”

Blog Name