Scientists Seek New Medicines From the Ocean

Sharon Kay
The Boston Globe
August 7, 2001
It grunts, it drools, and it's about as sluggish as a couch potato. But the aptly named toadfish—whose spiky face only a mother toadfish could love—can make world champion sprinter Michael Johnson look like a slow poke.

Blessed with the fastest twitching muscles in the vertebrate world, the toadfish can vibrate its swim bladder muscle an astounding 200 times per second, more than twice the speed of a rattlesnake tail and at least 40 times faster than the strides of the hapless Johnson.

Male toadfish use their bladder muscles to dazzle females with a unique mating call that sounds like a bullfrog. But, these days, toadfish are also wooing scientists who want to apply lessons of toadfish anatomy to everything from heart disease to human nerve regeneration.

After all, muscles that can contract and relax as fast as a toadfish bladder could provide clues on how to help failing human muscles of all kinds.

"When you want to develop a new system for a Ford Escort, you use the Formula One model to see the extreme version of motor performance," explained muscle physiologist Iain Young, who is spending the summer at the Marine Biological Lab in Woods Hole, Massachusetts, to study the Formula One muscle of the sea.

Once regarded as either dinner or a research novelty, creatures of the sea are getting increased respect among scientists looking for the medicines and therapies of the future.

From the ancient horseshoe crab, whose blood provides a common test for bacterial contamination, to the lowly sea urchin, which played a key role in test-tube fertilization of embryos, marine life is starting to take its place alongside more established lab animals, such as the mouse, in medical and basic biological research.

"I believe marine organisms can be used to eliminate disease and human suffering," said William Speck, a pediatrician who is now director of the Marine Biological Laboratory in Woods Hole. "We now have the technology to visit the deep ocean floor, and, because of DNA technology, to more deeply understand life and ourselves."

In truth, researchers at the Marine Biological Lab have been plumbing the sea for biomedical knowledge for a long time—arguably longer than anyone else. Launched in 1888 by "17 biologists and a row boat," the independent lab has grown into a summertime mecca for life sciences, drawing researchers from all over the world.

But, as the pace of medical research has quickened in recent years, the Marine Biological Lab—one of just a handful of labs focused on using marine life for biomedical research—has seen its position in the world rise, too. Federal grants to the small lab have risen more that 50 percent in the last five years, from U.S. $9.2 million in 1996 to $14.2 million this year.

In addition to covering three quarters of the planet surface, oceans support the greatest variety of life on Earth, many of them adapted to extreme environments—fish that can see in pitch blackness, marine mammals that can accurately find the source of sound underwater, creatures that thrive at pressure levels that would kill a human.

Understanding how these animals function enables scientists to experiment with more complex mammal systems in order to understand and cure diseases.

Insights Into Human Diseases

The sea is calm, the sun is radiant, and the clouds are slowly rolling in off the coast of Gay Head on Martha's Vineyard as two fishermen haul in nets loaded with more than 50 skate fish. Though the scene is vintage New England, these fishermen are working for scientists back at the Marine Biological Lab who are fascinated by the skates' unique eyes.

"The way you identify disease is its variation from normal. If you don't know what normal is, you don't know disease. From the skate retina, we've learned what's normal," explained Harris Ripps, an ophthalmologist and neurobiologist based at the University of Illinois in Chicago.

Though Ripps spends his summers at Woods Hole studying fish eyes, his real interest is diseases that damage the human retina, the light-sensitive tissue that lines the back of the eyeball. In particular, Ripps is concerned about retinitis pigmentosa, a disease that can lead to total blindness and affects an estimated 100,000 Americans.

The human retina contains two kinds of light-sensitive cells—rods, which allow people to see peripherally and detect light, and cones, which can distinguish color and distinct objects.

But Ripps and his colleague, John Dowling, a Harvard neurobiologist and president of the Marine Biological Lab, discovered early on that skates made a useful model for studying the human retina because they can detect light in the darkest and lightest condition using only rods.

By focusing on skates, the researchers could focus on what goes wrong in rod cells that can lead to blindness.

As a result, Ripps and other scientists understand that a single defective protein can corrupt the rods, and they are studying how this protein is communicated between cells through the use of genetic engineering.

Though they still haven't discovered a cure, doctors have found effective means of slowing down the disease in some patients. Minimizing exposure to light and doses of vitamin A have produced some positive results.

Ripps said he believes that through basic research, he and other scientists have unraveled part of the puzzle.

Common Biological Functions

Researchers studying cardiomyopathy—where the heart muscle loses the ability to relax normally and cannot properly pump blood—hope that toadfish muscles can help them the way that skates' eyes are aiding the study of blindness.

"In my studies of the toadfish, I've hypothesized that there is a molecule that helps it to relax as quickly as it does," said Larry Rome, who studies toadfish both at the University of Pennsylvania and at the Marine Biological Lab.

That molecule, a protein called parvalbumin, is found in human skeletal muscles but not in the heart. Some researchers, such as Joseph Metzger, a muscle physiologist at the University of Michigan Medical School, are examining how the human heart afflicted with such diseases as cardiomyopathy could benefit from inserting this protein.

But the toadfish's value may extend beyond heart disease. Though it barely has to move much of the time, somewhere in the evolutionary process the toadfish developed an unusual ability to regenerate its central nervous system.

"There is a curiosity about why this stage developed in evolution. It's not necessary for a fish to regenerate, so why does it and why not humans? The cues to guide nerve regeneration in fish could be important to humans," explained neurophysiologist Al Mensinger of the University of Minnesota at Duluth.

Mensinger is working with a technology that will allow the study of toadfish behavior in its natural habitat by monitoring neural activity leading into its brain. Scientists have learned that, unlike the human spinal chord, which, when cut, will fail to regenerate, the toadfish nerves grow back completely.

By implanting electrodes in the toadfish, they have watched the tissue regenerate in less than a month and actually grow through the holes of the device. One day, Mensinger said, the toadfish research may lead to advances in prosthetic devices for people with central nerve damage.

Part 2: A deadly snail from Fiji and the lowly horseshoe crab could hold keys to blood diseases and to protection from microbes from other worlds. Go>>

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