Studying genetic variation in fish is just one way that marine life can shed light on human health and development. While the Center for Marine Genomics focuses on fish as animal models, other endeavors at the Rosenstiel School are exploring the little-known but grand interplay between dwellers of the land and sea.

“Fish genomes are being used to define human genes and their function,” says Crawford, noting that a new type of genetics technology called a microarray is speeding the process. Microarrays enable scientists to view thousands of genes simultaneously in a small tissue sample. The ultimate goal, according to Crawford’s colleague, marine biology and fisheries professor Pat Walsh, is to identify the function of all the genes in an organism and to understand how those genes are coordinated to respond to the environment. Using the marine models works wonderfully, particularly when it comes to delicate and complicated matters such as cardiac health. After all, as Crawford points out, “We can’t take out human hearts and do it.”

“We’re trying to take the August Krogh Principle—‘For many problems there is an animal on which it can be most conveniently studied’—a step further,” Walsh explains. (In 1896 the Nobel Prize-winning Krogh experi-mented on Corethra larvae to show similarities between the functions of their air bladders and the diving tanks of submarines.) Walsh’s subject of choice is the toadfish, which he says is extremely tolerant of ammonia. “It’s a marine champion, if you will,” he states proudly. “In the mid- to late-1980s, basic research showed that the toadfish excretes urea instead of ammonia, which is very unusual for a fish. It piqued our curio-sity, and that led to studies of ammonia tolerance.”

The goal of such studies is to figure out exactly which mechanisms toadfish use to tolerate the ammonia, a waste product that a human liver cannot filter out when damaged by environmental factors, genetics, or alcoholism. Walsh believes these studies can lead to the development of a clinical strategy or drug that will aid humans in tolerating more ammonia during the onset of disease. “So it sort of illustrates another basic principle: all the research is important,” Walsh says, “because you might be studying the species for one reason and you discover something unexpected that leads to important developments.”

he idea of studying marine models for answers to human health questions is far from new. Michael Schmale, M.S. ’80, M.S. ’85, Ph.D. ’85, a genomics professor at the Rosenstiel School who studies neurofibrotumors in damselfish, began his work on the species in 1980. “Basically, this research involves a naturally occurring tumor found on species of fish common in Florida and the Caribbean. If you go out to Molasses Reef in Key Largo, the fish look specifically different—they have hyper-pigmented spots and lumps and bumps all over their bodies. The most common species, the bicolored damselfish, is very territorial; it stakes out a piece of reef and stays there its whole life. You can go out to a particular spot of reef month after month and follow the same fish to document the progression of these tumors in the wild. When they disappear from their territory, you can conclude they’ve died.”

The tumors on these fish are of two types. Those that form the hyper-pigmented spots are the equivalent of melanoma. The larger tumors, called neurofibromas, mimic the tumors caused by the human disease neurofibromatosis, a genetic disorder that causes tumors to grow along various types of nerves and also can affect the development of non-nervous tissues such as bones and skin. “The human disease is a very important one because it’s fairly common and affects 1 in 3,000 babies born,” Schmale says. “Half have learning disabilities and tumors in large numbers, and while most aren’t life-threatening, they are disfiguring and can be incapacitating. The damselfish is one of the few good models on which to study this.”

There are, however, some very significant differences between the fish’s cells and human cells. The human version of this disease is caused by the mutation of a gene. “So if you have it, your kids have a 50 percent chance of getting it from you,” Schmale says. In fish, however, it is transmissible through an agent, which makes it easier to study in a laboratory. “That is one of the most exciting things about this research program,” Schmale con-tinues. “We thought it would be a straightforward model of human disease, but we were totally surprised when we found it was transmissible. This could have huge implications on a wide area of research that we couldn’t have predicted at all. In a year or two, there could be big breakthroughs in discovering how this virus replicates.”

chmale’s colleague at the Rosenstiel School, Lynne Fieber, M.S. ’83, has for years studied the electrophysiology of the damselfish—and made her own surprising discovery in the process. Fieber analyzed tumor cells in a culture dish and, using a technique called patch-clamping, which allowed her to control passage of potassium ions across the cell membrane, concluded that blocking the passage of potassium controlled the growth of the cancer cells. “Even though the disease is the same in fish as it is in humans, you can’t do such a study on humans,” she explains. “A person who has the disease might have surgery to remove a tumor, and if the scientist is in communication with the patient and the surgeon, he might be able to get a culture of the tissue. But without the normal human tissue to compare it to, it doesn’t help. That’s the great value of marine animals—you can study both at the same time.”

Eventually Fieber was able to parlay her work to a tissue culture model of the human disease using human tumor cells she received from researchers at the University of Florida and normal human cells she received from research professor Patrick Wood at The Miami Project to Cure Paralysis. It’s an example of how cooperation between different institutions with mutual scientific interests is becoming not only more common, but also increasingly necessary for significant progress to be made.

“Now whenever I have a question, I go to the fish, then confirm my hypothesis with the human cells,” Fieber says. Her findings thus far have led her to believe that ion channel blockers may eventually prove useful in the treatment of certain types of neurofibromas.

iomedical research at the Rosenstiel School focuses not only on individual diseases but also on the big picture of the many ways in which the oceans and marine life can impact human health. Recently the National Science Foundation (NSF) and the National Institute of Environmental Health Sciences (NIEHS) jointly dedicated $5 million annually for the next five years to create four Oceans and Human Health Centers. The agencies have selected the Rosenstiel School to host one of them, the Center for Subtropical and Tropical Oceans and Human Health Research, which will examine the effects of harmful algal blooms (HAB), marine pathogens, and the oceans’ potential for drug discovery.

“This center represents a new collaboration between NIEHS and NSF,” says Lora Fleming, M.D., codirector of the Rosenstiel School center. “It’s basically a kind of ‘forced marriage’ of scientists from the oceanographic and biomedical sciences to get them to start looking predominantly at coastal problems, since that’s where humans interact the most with the marine environment.”

The partnering of Fleming, an environmental physician and epidemiologist at the School of Medicine, and codirector Sharon Smith, B.S.Ed. ’87, a biological oceanographer, is part and parcel to the center’s design—all research projects will include both a biomedical and an oceanographic scientist as principal and co-principal investigators. Other participating investigators are based at the Rosenstiel School, as well as the School of Medicine, Colleges of Arts and Sciences and Engineering, Centers for Disease Control and Prevention, Miami-Dade County Department of Health, Florida International University, and the University of Florida. Each of the center’s three research projects targets coastal problems that directly impact not only Florida but also the Caribbean and other subtropical coasts. “This is not just a Florida phenomenon,” Fleming is quick to point out. “It’s even more of a problem in developing nations, where people depend heavily upon marine waters for food, work, and recreation.”

One of the projects, HAB Functional Genomics, is, as Fleming puts it, “our own special one.” This is because Karenia brevis, the single-celled organism that most commonly causes red tide, flourishes off the Gulf Coast of Florida. K. brevis produces brevetoxin, a powerful and complex biotoxin that can kill a fish on impact; get absorbed into shellfish, thereby causing food poisoning in those who ingest them; and as an aerosol cause illness in humans, particularly those with asthma and respiratory problems. This study will evaluate at the DNA level why the K. brevis organism blooms and produces its toxins, as well as how these factors interconnect with environmental conditions such as currents and weather.

Another source of marine toxicity is wild phytoplankton, a topic on which a phytoplankton ecologist from the Rosenstiel School is working with a toxin chemist from Florida International University. Their research will seek out new biotoxins in identified and unidentified marine organisms. Based on prior experience, it is possible that some of these toxins may have therapeutic value. For example, synthetic and natural derivatives of brevetoxins have been patented for possible treatment applications in cystic fibrosis and other lung diseases.

Compounding the presence of naturally occurring toxins is microbial contamination of our beaches (“in layman’s terms, that’s from poop,” chuckles Fleming), which can sicken or kill livestock, marine life and birds, and humans. As more and more people spend time working and playing on our beaches, microbial contamination becomes an important economic and health issue. A research project pairing an environmental engineer with a physical oceanographer will evaluate the measurement, exposures, and health effects of these microbes (bacteria, viruses, and parasites) in recreational marine waters in Miami.

cientists are just beginning to explore the vast opportunities for medical knowledge harbored by the sea. Centers and projects that unite experts in biomedical and oceanographic sciences hold great promise for advancing this knowledge.

“In the past ten years, there’s been more interdisciplinary work than ever before,” Fleming says. “The more scientists you have working on these things, the more you find out. At first you spend a lot of time trying to figure out each other’s vocabularies. But once you get through that, you go to new places and get much richer research.”