A red eyed tree frog is most striking in its coloration. Source: FrogsONice.com

Tyrone Hayes is an associate professor of integrative biology at the University of California,

Berkeley, and he is crazy about frogs. There are literally hundreds of “froggy” paraphernalia adorning his laboratory, peeping out from behind his books, stuck to the refrigerator, and staring goggle-eyed at each student visiting his office hours.

Hayes grew up in South Carolina, and as a child he loved to explore swamps. He fondly remembers his favorite book, a gift given to him by his grandmother, What is a Frog? In one of his very animated presentations on his current research, Hayes told his endocrinology students, “I was fascinated by how one cell could turn into a tadpole, and further turn into a frog … a completely different organism! One is aquatic and is able to swim and has gills, while the other has four legs, hops around, and breathes with lungs on land.”

It turns out that Hayes’s passion for these unique organisms is well founded. Frogs have proven to be important in deciphering endocrine function and alteration; the hormones found in frogs are the same as found in mammals, including humans.

As an endocrinologist, Hayes investigates the hormone-dependent features of frogs and the potential implications frog population development, coloration, and behavior has on both conservation and human health. In a study of African Hyperolius frogs from Ethiopia and Uganda, also known as reed frogs, Hayes and his team examined highly varied color polymorphisms and how they may be affected by hormonal changes in or to the frogs. The study was presented in National Geographic magazine as well as scientific journals.

“In the African clawed frog, for example, colorations are due to testosterone and estrogen levels,” Hayes explained to his Berkeley students as he showed them what appeared to be two completely distinct species. The two “different” species were in fact one and the same.

“Another example is when you inject a tadpole with thiourea and disable its proper levels of thyroid hormone: The tadpole becomes an abnormally giant tadpole and not a frog.” Frog skin, laryngeal sacs, size, shape, sexual development, and behavior can all be altered by chemicals. The drastic effects that hormonal injections or blockages have on the frogs’ morphologies have led to Hayes’s use of this exciting “frog bioassay.” By studying the effects of hormones and other chemical compounds on frogs, humans can determine the extent to which water sources or lands are contaminated in a cost-effective and efficient manner.

A normal and healthy gecko frog. Source: AllAboutFrogs.org

Specifically, Hayes has chosen to focus on environmental pollutants that produce changes in frog endocrine functions. He has traveled all over the world studying frogs and other amphibians. When asked, he recalls with a smile, “I’ve been to Congo, Uganda, Ethiopia … well, pretty much all of East Africa. I’ve been all over Europe and Asia. I’ve even been to Turkmenistan, which is North of Iran. I went to a conference there because that’s where you find both Central Asian animals and Central European animals, and a unique mixture of living organisms of the two regions.”

Currently, Hayes is zeroing in on the use of atrazine, a weed-killer that has been used for more than 40 years in the United States on monocot crops. More than 150 million pounds of atrazine are used each year. “I formulate a lab model, use that for comparative studies, then move on to field studies and field simulations, and bring all this back to the lab,” he explains to his lecture students. “Atrazine is an endocrine-disruptive herbicide … it has effects on frog gonadal growth, laryngeal growth, and developmental growth in terms of metamorphosis.” Hayes strongly asserts, “This is relevant to us. There is a direct link to human biology.” What affects our amphibious friends can also affect us.

Even very low levels of toxins in the environment (both in the lab and in the field) have proven to irreparably damage frog systems. Hayes tells his stunned students during a slide presentation of mutated frog tissues, “I mean, atrazine is bad but there are a number of chemicals in use. Just one low dose turns this species into a hermaphrodite. A mixture is worse (such as in runoff from nearby crop field into the lake where the frogs live). There are other bad effects too.”

Some frogs can become hermaphrodites (animals with both testicular and ovarian tissue), but even the degree of hermaphroditism goes from bad to worse. According to slides taken from the Hayes lab at Berkeley, some of the male frogs can reach a state where their testicular tissue is literally exploding with eggs. The list of anomalies in these little animals due to chemicals that humans disperse is quite long.

The mechanism of hermaphroditism is one of active feminization and demasculinization; atrazine turns on the enzyme aromatase, which turns the hormone testosterone to estrogen. Atrazine inhibits laryngeal growth in male frogs as well. While the EPA standard for atrazine levels in water is three parts per billion (ppb), the Hayes lab found that even 0.1 ppb causes abnormalities in frogs.

A deformed frog with an additional back right leg, found in Minnesota in 1996. Source: Minnesota Pollution Control Agency

Actually, low doses sometimes result in more severe effects than high levels. This is analogous to hormonal changes causing reproductive changes in a woman’s body. Low dosages of estrogens induce egg development and uterine lining growth (i.e., prepare for pregnancy), but high dosages do none of these things and in fact are used in birth control pills. Likewise in male frogs, low dosages of atrazine induce abnormal egg development in the testes, while high doses do not.

“Yet amazingly, many frogs don’t die,” continues Hayes. “They adapt and find ways to avoid the toxicants and pollutants in their environment. They develop differently, act differently, and reproduce and recover at different rates.
“Also, I’m not only interested in just one chemical. There is no single chemical anywhere! I want to know what mixtures of chemicals do, and how they affect multiple species.”

The Hayes laboratory typically employs 10 undergraduates, who have written research papers for Nature and other distinguished publications. This links to Hayes’s distinct teaching philosophy toward his students: “You should know all that I know.” He is quite happy to say to his lecture students, “I don’t know the answer to your question. But you know what? No one knows right now! I can even go next door to my fellow professors who are working on this stuff right now and find out, but they still might not know! That’s what makes it so exciting!”

The endocrinology curriculum for his class constantly changes based on current research, and his exams emphasize a fresh approach using foundation knowledge. In his words, “I want to understand what your limit of knowledge is and push it to the limit. I want you to know how to figure out things in a new context.” For example, after teaching his class about the major hormones that are involved in osmoregulation, Hayes asks, “So me and my daughter are in the desert and she’s thirsty. I give her lots of water. Why doesn’t my daughter explode?”

Hayes’s research will continue to examine the morphological, behavioral, and developmental changes that frogs undergo due to chemicals and mixtures of chemicals. His frog assay allows for a definitive and inexpensive method to determine the level of pollutants that surround human populations, especially in countries that cannot afford lots of high-tech research and analyses on their water and farmlands.

Hayes hopes to formulate a simple model of amphibians that will allow him and others to generalize information to populations and eventually to ecosystems. His research and instruction are truly integrative; they encompass the fields of embryology, endocrinology, ecology, genetics, behavioral science, evolution, public health, and conservation biology, just to name a few. His passionate pursuit for knowledge, as well as his youthful character, makes for a person who is both a mentor and a friend.