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http://www.wired.com/news/technology/0,1282,49185,00.html?tw=wn20011224

Why Goldfish Might Turn Blue
By Dermot McGrath

2:00 a.m. Dec. 24, 2001 PST

Say goodbye to Birkenstock sandals and woolly jumpers -- tomorrow's
eco-warrior will like nothing better than swimming naked in defense of
cleaner oceans.

That, at least, is the hope of researchers in Singapore, who are developing
a breed of fish capable of detecting water pollutants by changing color.

Scientists at the Department of Biological Sciences at Singapore's National
University ( http://www.nus.edu.sg/ ) intend to produce commercially viable
zebra fish that can be used as a simple, cheaper alternative to current
pollutant-testing systems.

Zebra fish are usually black and silver in color, but through genetic
manipulation researchers have produced a few varieties that radiate green or
red fluorescent color.

Scientists have so far succeeded in isolating two types of gene promoters in
the zebra fish -- an estrogen-inducible promoter and a stress-responsive
promoter. These promoters -- the part of the gene that contains the
information to turn the gene on or off -- have been used to drive the
fluorescent color genes in transgenic zebra fish. A transgenic organism is
one that contains genes from another species. According to researchers, such
zebra fish will be able to respond to the presence of chemicals like
estrogen, heavy metals and various toxins in water.

"The most significant benefit of the biomonitoring fish is the possibility
to develop an online system to monitor aquatic environment and water
quality," project leader Zhiyuan Gong, associate professor in the Department
of Biological Sciences at Singapore's National University, said. "Compared
to conventional chemical measurement, the live fish can tell us the
biological effect of the pollutants."

The fish will immediately display the color depending on the type of
environment the color has been specified for. Although only red and green
colors have been produced in the zebra fish thus far, Gong and his team
believe that they can produce up to as many as five colors, with each color
indicating a different pollutant.

The main advantages of such transgenic fish is that pollutants can be
detected with one quick look, and the fish are also economical to breed and
biodegradable. All these factors make them very suitable pollutant
indicators, said Gong.

Other researchers warn, however, that significant hurdles need to be
overcome before transgenic fish can ever be commercially deployed as
pollution indicators.

"Any truly useful environmental monitoring tool should give us a signal
which can be interpreted ecologically," said Donald Baird, a researcher with
the environment group at the Institute of Aquaculture
http://www.stir.ac.uk/Departments/NaturalSciences/Aquaculture/ ) in the
University of Stirling in Scotland.

"Molecular genetic signals such as color-changing fish are merely proxies
for chemical analysis -- they tell us nothing about quantity of the
substance present, merely that a threshold has been passed at a specific
receptor site in the organism," he said.

Baird believes that a more sensible approach would be to work with gene
micro-arrays, which offer the possibility of simultaneously detecting a wide
range of pollutants by examining the regulation of proteins.

"This would be a cheap and non-destructive method of assessing chemical
exposure. And it would not involve the use of live vertebrates which is now
seen, quite rightly, as ethically untenable in routine monitoring and is
gradually being phased out," he said.

Gong estimated that it would take at least another year before the project
moves beyond the experimental phase.

"We can create such monitoring fish now using our existing techniques.
However, we are still not sure how (sensitively) the fish can monitor
environmental pollution and will need to do a lot of fine-tuning work," Gong
conceded.

Besides zebra fish, marine species such as the carp and goldfish can also be
genetically engineered to display different fluorescent colors. The
Singapore team is working toward producing fish that give off a
different-colored glow depending on water temperature, which may lead to
using fluorescent fish as temperature indicators.

Richard Winn, associate professor of the Aquatic Biotechnology and
Environmental Lab at the University of Georgia ( http://www.uga.edu/ ) said
this is not the first time transgenic fish have been proposed as possible
pollution indicators.

"The concept of the environmental 'sentinel' is not new -- fish and other
critters have been doing this for quite some time," he said.

Winn is also skeptical that color-changing fish can offer a radical
alternative to current pollution-monitoring techniques.

"An important requirement of a test system is that it should provide an
indication not only of the presence of a toxic chemical but also a graded
response relative to the amount of chemical present," he said.

"While it is valuable to know the organism has been exposed to compound ABC,
it is often even more helpful to know that the organism was exposed to X
amount of the compound, which produced the Y effect. Quite simply, any
system that can provide a quantitative measure of a response is very
valuable."

Winn points out that even assuming the initial tests show the system works
as planned, it may be a significant hurdle to actually receive permission to
release the genetically modified fish in the wild.

"There is some difference in opinion about the real or imagined impact of
releasing transgenic fish into the environment," he said. "Depending upon
the fish species and the transgenes used, the possible impacts could range
from inconsequential to localized extinction of native species. This should
be studied thoroughly before any release is considered."

A study last year by researchers at Purdue University
http://www.purdue.edu/UNS/html4ever/0002.Muir.trojan.html ) concluded that
transgenic fish could present a significant threat to native wildlife, even
to the point of extinction.

Anne Kapuscinski, professor of Fisheries and Conservation Biology and
founding director of the Institute for Social, Economic and Ecological
Sustainability (ISEES - http://www.fw.umn.edu/ISEES/ ) at the University of
Minnesota, agreed that a lot more research needed to be carried out to
assess the potential risk of releasing transgenic fish into the environment.

"In some fish species, adults of one gender or the other use color to
attract mates and successfully reproduce. Genetically engineered changes in
external color might interfere with the mate-attraction strategy in harmful
ways or might have little or no impact," said Kapuscinski.

She stressed the importance of conducting ecologically relevant bio-safety
studies to credibly assess environmental risk at an early stage in the
research and development of transgenic organisms.

"So far, researchers have been waiting until much too late in the R&D
process to enlist qualified fish biologists and ecologists to address the
bio-safety questions," she said.

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