50 years of Gatorade
This year marks the 50th anniversary of one of UF’s most important research discoveries — Gatorade. Gatorade not only launched a sports beverage industry, it also created a culture of innovation that persists at UF Health today.
By Morgan Sherburne
Drs. Alejandro de Quesada, J. Robert Cade, Jim Free and Dana Shires invented Gatorade in a basement lab.
Fifty years ago, in a basement lab in the UF Health Science Center, J. Robert Cade and three research fellows, Alejandro de Quesada, M.D., Jim Free, M.D., and Dana Shires, M.D., sought to find out why football players could not urinate after playing in the brutal Florida heat. This one research question led, of course, to the most well-known and commercially successful invention in UF history — Gatorade.
Although Gatorade is known most for its effects on the field, quenching players’ thirst and drenching winning coaches after big games, the beverage has had, perhaps, an even greater effect away from the sidelines. Cade was proud of Gatorade’s clinical use in helping to rehydrate sick children. The drink also sparked a legacy of innovation at UF, both by example and with the more than $250 million in royalties that have helped fund research across campus, particularly in the College of Medicine.
As we celebrate the 50th anniversary of Gatorade, The POST is taking you on a four-part journey exploring some of the research projects and places this innovative beverage has helped make possible. Our first stop? The division where it all started.
A legacy that began in a nephrology lab
Division of nephrology
Sitting just below the stomach alongside your back are a pair of organs you likely think of only when you’ve had too much coffee on a long road trip.
The kidneys separate waste products from usable energy and release that waste through urine. For coffee-drinking road trippers, that the kidneys perform this job is almost a nuisance. But for the body, they are anything but. By regulating acids and salts in the blood, the kidneys control blood pressures in the body.
“The kidneys are really what regulates what’s in our blood, and they’re responsible for getting rid of the waste products that all our cells generate,” says David Weiner, M.D., a co-holder of the C. Craig and Audrae Tisher chair in the department of medicine’s division of nephrology, hypertension and renal transplantation. “When the kidneys don’t work, the ability to stay healthy is lost.”
Fifty years ago, another famous nephrologist — Cade — was in the middle of his career, studying the importance of the kidney and treating kidney diseases. Cade and a team of researchers recognized the need to replace electrolytes lost through sweat from football players’ bodies as they played in the brutal Florida heat. In creating the sports drink, they also laid the foundation, both ideologically and through research support from Gatorade royalties, for innovative research that still persists in the College of Medicine’s division of nephrology, hypertension and renal transplantation today.
“We have a number of different pockets of research, ranging from cardiovascular health as it relates to patients with chronic kidney disease to studying why women who undergo assisted reproduction therapy are at an increased risk of heart attack,” says Mark Segal, M.D., Ph.D., the J. Robert Cade professor of medicine and division chief.
Segal focuses on the relationship between patients with chronic kidney disease and cardiovascular risk, including heart attack and stroke. Using funds from Gatorade, Segal is developing a mouse model to study the relationship between acute kidney injury and the increased risk of cardiovascular disease.
Support from Cade’s legacy may have helped Weiner’s research group become one of the most proficient in the world.
His group has used Gatorade money as a launching pad to study blood proteins, and found these proteins were essential for controlling the amount of acid and antacid in the blood.
“Abnormal amounts of acid or antacid can lead to a wide variety of undesirable things, from kids who can’t grow normally to adults having kidney stones to worsened control of diabetes and people with kidney disease needing dialysis treatment,” Weiner says.
To neutralize acid the body normally produces, kidneys generate antacid. If the kidneys can’t generate enough antacid, acid can cause bones to start breaking down — leading to a lack of growth in children, the development of kidney stones and osteoporosis, a condition in which bones become porous and prone to breaks from even light stress. An overload of acid can cause muscle to break down as well.
“We’ve used the money to support projects that were important for us and that were necessary to take us in new directions that were very exciting,” Weiner says. “That investment has now paid off. In the last 10 years, we’ve gotten close to $5 million in funding.”
Charles S. Wingo, M.D., who co-holds the C. Craig and Audrae Tisher chair, studies, among other interests, the role of two substances, aldosterone and endothelin. Aldosterone, a steroid hormone, is produced by the adrenal gland and helps regulate blood pressure by controlling sodium, potassium, ions and water in the kidney. Aldosterone stimulates endothelin, which modifies sodium retention by the kidney.
His research group showed that a renal aldosterone-endothelin feedback system plays a role in regulating sodium retention in the kidney.
“If this system is defective or inhibited in some fashion, aldosterone can cause uncontrolled salt retention by the kidney,” Wingo says. “We’ve been able to demonstrate this in animals, and this helped us formulate a hypothesis for explaining certain forms of essential hypertension.”
Wingo credits Gatorade’s funding in helping his lab spur some of his research.
“The funds provide a mechanism for us to develop new projects,” Wingo says. “These funds can then be used to provide preliminary data that are essential for extramural funding.”
Wingo’s time at UF overlapped with Cade’s.
“He was quite a unique and wonderful man — an excellent lecturer and great raconteur,” Wingo says. “He was truly a creative thinker and had many different interests.”
Cade was an assiduous, innovative researcher. He hoped Gatorade would save the lives of children with diarrhea in developing countries. He invented a nutrient-packed shake that would help patients recover from surgery. He studied how dialysis could be used as a cure for schizophrenia and how diet might affect the well-being of children with autism.
“I truly believe this division is innovative, and that innovation has its origin with Dr. Cade,” Segal says. “He never accepted the status quo. Dealing with a population of patients with end-stage kidney disease who have a five-year mortality of 50 percent, we shouldn’t accept the status quo, either.” — Morgan Sherburne
Help for Haiti
Tuberculosis was a problem in Haiti long before the earthquake that devastated the island nation in 2010. According to the Centers for Disease Control and Prevention, Haiti has the worst rate of TB in the Western hemisphere, not even accounting for all the cases that go undiagnosed. The physical damage, failing infrastructure and displacement of the population that followed the disaster only made
matters worse.
After a disaster, relief efforts often address short-term needs, which is one of the reasons why Michael Lauzardo, M.D., director of the Southeastern National Tuberculosis Center and chief of the UF division of infectious diseases and global medicine, wanted to focus on long-term solutions to combating the problem of drug-resistant TB in Haiti.
“There were so many people who had lost so much and so many people trying to get involved,” Lauzardo says. “We wanted to develop a long-term relationship, establishing research projects and service. Haiti is Florida’s neighbor; throughout our own UF community and Florida as whole, we have many ties to Haiti. There is an opportunity for us to be part of a new era for Haiti.”
In 2014, with the help of $200,000 from the Gatorade Trust, UF opened a lab in Haiti to perform rapid diagnostic tests, train lab technicians to do this work and conduct research tackling major research questions related to transmission of the disease and certain strains’ resistance to treatment.
According to the World Health Organization, 5 percent of TB cases are resistant to the most common treatments. Treating this form of the disease requires quadrupling the amount of time patients need to be treated and almost doubling the medicines they take. It also comes with increased risks for complications, such as blindness, liver failure and death. For a country like Haiti, which is ill-equipped
to deal with TB cases that do respond to treatment, drug-resistant TB is particularly problematic.
Dr. Michael Lauzardo and his graduate assistant Nancy Seraphin are working to understand drug-resistant TB in Haiti. With the help of a grant from the Gatorade Trust, Lauzardo established a lab in Haiti.
“There are a lot of challenges in Haiti,” says Lauzardo, also a member of the UF Emerging Pathogens Institute. “Many of the reasons are historical and structural. There are lots of reasons for these challenges beyond (the people’s) control. Having support to try new things like Gatorade has provided us is key. Gatorade’s funding has helped us do something novel and unique and efficient but it moves research forward.”
Connected to the UF Public Health Laboratory in Haiti, the UF TB Lab maintains a biosafety level 3, meaning it is equipped to safely study TB, a highly infectious pathogen. By contrast, Ebola, requires biosafety level 4. To create a BSL-3 lab in Haiti, they teamed with bioBUBBLE, which created a 309-square-foot containment environment inside the 1,500-square foot facility.
“It’s built to withstand an earthquake and has all containment criteria we have here in the EPI. It’s fully operational,” says Nancy Séraphin, a doctoral student in the College of Public Health and Health Professions and Lauzardo’s graduate assistant.
Inside the lab, researchers are performing rapid diagnostic TB tests to more quickly diagnose people with the condition. In addition to this service, UF researchers are working with the Laboratoire National de Sante Publique in Haiti to train Haitian lab technicians to perform these advanced tests.
With samples collected at the Haiti lab, UF researchers will also be able to work toward answering some of the research questions surrounding TB in Haiti, such as how it becomes drug-resistant, the different strain lineages in circulation, how they evolve and affect disease presentation and treatment outcomes.
“TB is interesting because it can remain latent throughout your lifetime,” says Séraphin. “You may be infected but not sick or infectious. But then as you grow old or if your immune system becomes compromised, you may develop TB disease. In Haiti, you have upward of 200 per 100,000 people getting the disease each year; many of them are recently infected. In the U.S. currently, we see three cases of TB per 100,000 people a year. There is a wide difference.”
A native of Haiti, Séraphin still has extended family members who reside there, so the work she is doing with Lauzardo is particularly meaningful for her. As a public health practitioner working in Haiti, Séraphin realized how overlooked TB was as a public health problem while researching a grant.
“It wasn’t that the government didn’t care, there just was not enough resources,” she says. “That motivated me to work with Dr. Lauzardo because he wanted to do this and I had intimate knowledge of what was going on in Haiti. He offered me this opportunity and I jumped at it.”
Moving forward, Lauzardo hopes to expand his team’s work to help people with drug-resistant TB not only by testing for it and conducting research, but also by devising effective ways to combat the disease and treating patients there, too.
“We want to move research into how to best provide drug-resistant TB therapy in a difficult environment, how to best get specimens to lab, how to get people complicated therapy far away from lab so Haiti can be a leader,” he says. “We want people to look to Haiti and think Haiti fixed this problem of drug-resistant TB. Haiti can lead on this and we want to be part of that with them.” — April Frawley Lacey
Seeking solutions for the body’s tiniest invaders
White puffy clouds dot blue skies over a sleepy beach town in the Caribbean. A local woman selling mangoes from a stand on the sand absently slaps a mosquito on her shoulder. A little boy playing in a pond feels a small sting behind his knee, then forgets about it later on.
A few days later, the symptoms set in — terrible headaches, high fever, a rash, joint pain, muscle pain or bone pain. The diagnosis is dengue fever, also known as “breakbone fever,” due to its painful symptoms.
There’s currently no medicine that can treat this disease, which is a leading cause of illness and death in the tropics and subtropics, according to the Centers for Disease Control and Prevention.
Because dengue travels into the bloodstream through mosquito bites, most people never see it coming. But virologist Ashley Brown, Ph.D., studies microorganisms such as dengue, and she hopes that someday her work will lead to therapies for this public health problem.
“Dengue is an important disease that affects millions of people worldwide,” says Brown, an assistant professor of medicine in the UF College of Medicine.
Brown received funding from the Gatorade Trust in 2014 to work on applying some of her previous work to dengue fever. At the UF Research and Academic Center at Lake Nona, she and her colleagues in the Institute for Therapeutic Innovation have created successful models to test drug dosing, delivery and efficacy for other viruses, including hepatitis C, HIV and influenza. She is using the Gatorade Trust funding to start adapting one of these models to dengue. To do that, the researchers must first grow sufficient amounts of virus, learn how to make the virus replicate in a system that mimics human blood, and determine how much virus is needed to keep the model system up and running.
Once dengue can grow and replicate in the lab, Brown faces the challenge of finding an antiviral drug that might kill the virus. To do this, she received a second Gatorade grant this year, which is allowing her to work with a company called Cloud Pharmaceuticals Inc. This company seeks potential drugs in silico; in other words, by using computer modeling. They enter the crystalline structure of a dengue virus protein called a protease into high-powered computers and use mathematical modeling to predict which chemical structures might serve as therapeutic medicines for the disease. Once the researchers have identified chemical compounds of potential interest, they will send the information to chemists who will try to create the compounds in the lab if they do not already exist in nature.
“Hopefully we can find a compound that will work,” Brown says.
It will not be a simple task. Dengue fever is caused by four or five different but related variants of the same virus. People who get one variant may experience no symptoms of the disease, but if they get infected by a second related variant, they can develop dengue hemorrhagic fever, which causes blood vessels to leak and can be fatal.
“It’s a pretty tricky virus,” Brown says. While she will study one particular variant of the virus, the goal will be to have a broad-spectrum therapeutic that would address all related variants of the microorganism.
Dengue fever is widespread in the Caribbean and Central America and other tropical areas where the weather stays warm year-round. The warm weather encourages the spread of the disease by Aedes aegypti and Aedes albopictus mosquitoes. In recent years, dengue has started to make an appearance in the United States, particularly in southern states such as Florida and Texas. Experts in the field say the chances of an outbreak of dengue in the United States are relatively high, Brown says.
Brown also plans to examine potential therapeutics for another virus that in less than two years has spread like wildfire through the Caribbean and Central and South America — chikungunya, a mosquito-borne disease that causes its victims to suffer long-term joint pain that can affect people’s lives and productivity. While chikungunya appeared in the Americas as late as December of 2013, it has already infected more than 1.5 million people.
“It’s important for us to develop drugs for some of these acute infections,” Brown says. — Melissa Lutz Blouin
A gem by the sea
At just 5 millimeters in length, the larval zebrafish darts across the petri dish of water, transparent apart from two black eyes that appear gigantic under the microscope.
Although tiny, this larval zebrafish is playing a big role in the lab of James C. Liao, Ph.D., a National Institutes of Health-funded researcher at UF’s Whitney Laboratory for Marine Bioscience. Liao is studying the zebrafish’s lateral line system, which contains hair cells similar to those found in the human ear. Using electrophysiology techniques, Liao is working to uncover how these cells help fish sense and respond to flow. For example, the flow of a predator nearby makes the tiny hair cells vibrate, which cause electrical signals to be sent to the brain. The process is similar when humans hear sound.
Understanding the mechanisms of how these cells work in a small, simple animal could help researchers shed light on similar mechanisms at work in humans, Liao says.
“The mechanisms of how this is supposed to work are not well-understood,” Liao says. “We need an understanding of what is happening in a healthy system. If your computer is broken, how do you know how to fix it if you don’t know how it is supposed to work?”
Because the fish are transparent, Liao and his team can see what is happening in the nervous system in the living animal, making zebrafish ideal creatures to study.
Understanding how the underwater world relates to human disease is the primary mission of UF’s Whitney Lab, which opened in 1974. The lab was the brainchild of Cornelius Vanderbilt Whitney, who donated the land and half the construction costs for the lab to UF. Money from UF, including a $30,000 grant from the Gatorade Trust, helped fund the rest.
Whitney, heir to the Whitney and Vanderbilt fortunes, had founded Marineland, situated on the ocean across from the Whitney Lab, in 1938. Originally founded as Marine Studios, where films such as “The Creature from the Black Lagoon” were made, Marineland was Florida’s first underwater attraction.
Noticing how marine animals did not seem to be susceptible to diseases that plague humans, Whitney later donated a swath of land nestled between the Atlantic Ocean and the Matanzas Inlet to UF to establish a lab that would use knowledge gained from the sea to benefit human health.
“He had noticed that large marine animals never seemed to get cancer and tumors,” says Mark Q. Martindale, Ph.D., director of the Whitney Lab. “He thought marine animals had solutions to human disease, so he initiated this lab, dedicated to biomedical research that leverages marine organisms in order to understand basic aspects of human health. And it has been remarkably successful.”
Through the years, researchers at Whitney Lab have studied creatures such as horseshoe crabs to understand the biochemistry of vision, jellyfish to understand the nervous system, lobsters to understand the sense of smell, or in the case of Martindale’s lab, a variety of sea creatures to understand how they evolve over time and develop novel features. What makes it all possible is a unique seawater system that pulls water directly from the ocean into the lab, making a more habitable environment for the marine creatures that reside at the lab.
“We can keep animals here that you can’t keep at other marine labs,” Martindale says.
Whitney researchers are finding ways to innovate outside of the lab, too. In 2014, Whitney Lab researcher Leonid Moroz, Ph.D., became the first to conduct genome sequencing of marine creatures such as rare comb jellies in real time while aboard a ship. Because of their fragile bodies, these creatures cannot be safely shipped to the lab, so the researchers brought the lab to them. Moroz, his team and colleagues from the Bimini Shark Laboratory and Florida Biodiversity Institute conducted the sequencing and analysis, linking to UF’s HiPerGator supercomputer, aboard the ship Copasetic.
“If you cannot bring the creatures to the lab, why not bring the lab to the sea?” Moroz says. “To learn from nature, we have to work in nature. We can do genomic sequencing in extreme environments, from Antarctica to tropical seas.”
The research could lead to better understanding of the mechanisms at work in these creatures and could lead to new drug discoveries.
Although the lab’s primary focus is research, over the years the role of education has grown there as well. Students from across North Florida visit the lab to learn about sea life and science, and in recent years, more UF graduate students have begun working and learning at the lab. The lab also hosts summer research programs for students and offers public lectures to the community.
Now, the Whitney Lab is poised to take on a patient care role with its new donor-funded Sea Turtle Hospital. The hospital will treat and rehabilitate sea turtles while Whitney researchers study a disease that plagues these animals, fibropapillomatosis.
Although Gatorade’s initial contribution to the lab was small, that seed has helped grow one of the most unique marine research programs in the country, dedicated to helping understand animal life and bettering human health.
“There are few places like this in the country,” Liao says. “The Whitney Lab is a little gem.” — April Frawley Lacey