In the body, crystals – made of substances such as calcium or urine collection – form masses that can cause pain and serious illness. University of Houston crystal expert Jeffrey Riemer, the Abraham E. Duclair Professor of Chemical Engineering, known worldwide for his groundbreaking discoveries using innovative crystal control techniques to treat malaria and kidney stones, reports a new method to control the growth of ammonium urate crystals , a substance known to cause kidney stones in dolphins.
Yes, dolphins also have kidney stones. And how did we find out? You can thank the Navy.
In fact, move on to fur seals – the bottlenose dolphin is another marine mammal that diligently protects our shores. Thanks to their highly developed ability to detect objects, dolphins have been helping the US Navy find underwater mines for decades as part of the US Navy’s Marine Mammal Program.
Through this program, the Navy takes good care of its dolphin friends by funding research into issues such as dolphin kidney stones. Riemer has been on a wave of dolphin research for some time, previously reporting crystals associated with dolphin kidney stones made of ammonium urate, which is rare in humans. He currently leads an international team of researchers from Tianjin University in China, Stockholm University in Sweden, University of Pittsburgh, University of Strathclyde, Glasgow in Scotland, Texas A&M University, Purdue University, National Polytechnic Institute of Mexico and the Molecular Foundry of Lawrence Berkeley National Laboratory.
On behalf of the team, Rimer published a new job at Communications of nature about their discovery of a method of controlling the growth of ammonium urate crystals by manipulating isomers of urate, called tautomers. The findings could not only help dolphins, but also have implications for the pharmaceutical industry.
“We found that the small fraction of urate that exists as a minor tautomer can control the rate of crystal growth to the point that it can completely block crystallization,” Riemer said. “The most unexpected and remarkable thing was to find that when you increase the concentration of urate, the rate of crystallization suddenly drops to almost zero, and crystals do not grow in that region.”
Rimmer believes that it is possible to mimic these results by controlling the diet to get kidney concentrations in this range, so then there is a chance that crystal growth will be inhibited and medication will be unnecessary.
This applies to both dolphins and humans, but that’s for future research.
While studying urate crystals, Riemer also discovered that tautomers are incorporated into the crystals as defects, and this is where these findings have implications for pharmaceuticals.
Among the top 200 drugs, there are 33 (including allopurinol, used to treat kidney stones) that are tautomers. These drugs affect millions of people worldwide and are prescribed for HIV, epilepsy, COVID-19, schizophrenia and cancer (skin, lung and pancreatic).
“When we made crystals with very few defects, they dissolved much more slowly, while crystals with a higher percentage of defects dissolved faster,” Riemer said. “This is very important for pharmaceuticals, because when you put a drug into your body, its effectiveness depends on how quickly it dissolves,” Riemer said.
“We’re asking the question about these 33 pharmaceuticals – do the companies really know the extent to which they have defects? The same question can be asked in nature, where tautomers can influence species-unique properties vital to their intended function, such as optical properties in fish or color changes in chameleons,” he said.
As Rimer’s research continues, these questions may soon be answered.
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