Super Test for Toxics’ Effect on Humans
Tucked away in a cramped corner of UC Irvine’s Southern Occupational Health Center sits a shiny new hybrid of high technology, a half-million-dollar machine that could unlock long-sought secrets about the effects of toxic chemicals on humans.
At first glance, the “interactive laser cytometer” looks like a fancy microscope with a couple of television monitors incongruously attached. But the innocuous-looking tube behind the monitors is a powerful Argon laser, and under the table sits the sophisticated computer that makes the apparatus run.
In the midst of all this machinery, in a tiny petrie dish, are some human cells, which, thanks to contemporary biotechnology techniques, can be grown and colored according to the needs of a particular experiment. When the whole thing is set in motion, researchers are able to discern, with digital precision, exactly how the cells respond to chemicals.
And that measurement is the beginning of a sequence of operations that Daniel Menzel, director of the center, says will help reveal the link between specific levels of chemical exposure and the development of certain diseases. That’s the kind of information that both occupational health specialists and environmental regulators are desperate to obtain.
“Everybody knows that smog is bad for you,” Menzel points out. “But the crucial question is: how bad?”
Like it or not, experts say it’s impossible to completely eliminate dangerous chemicals from the workplace or the environment, and logical regulations can be developed only on the basis of a “risk assessment” analyzing the exact effects of specific levels of chemical exposure on human health.
The traditional method of performing such studies relies on epidemiology--examining the health of people who have been exposed to the substances in question. Researchers who are trying to evaluate the dangers posed by household radon, for example, have examined miners who were exposed to the gas on the job, according to Dean Baker, an environmental and occupational medicine physician at the Mt. Sinai Hospital School of Medicine in New York.
But such studies have limitations. For many chemicals, there simply is no group of people who have been exposed over a long period of time, and it can be a hollow victory to discover the dangers only after some people have developed a terminal disease.
Furthermore, people are generally exposed to many different chemicals, both on and off the job, and it can be difficult to separate the effects. That problem is exacerbated when a study group consists of a small selection whose composition does not reflect the population as a whole.
Animal studies have thus become the mainstay of research on the health effects of chemicals, though they also have some obvious limitations. Even though the physiology of rats, for example, has some strong resemblances to that of people, the effects of a chemical won’t be exactly the same.
Menzel, a toxicologist by training who came to UCI a year ago after a 18 years at Duke University, believes that his 2-month-old cytometer--which he says is the only one of its kind on the West Coast--can provide solutions to some of these problems.
“This technique is going to burgeon,” he predicted. “By this time next year, there will be a dozen of these machines out here.”
What the cytometer does, the gregarious Menzel explained in a recent interview, is create a digital, three-dimensional model of a living cell. Just as a CAT scanner or a magnetic-resonance scanner creates a picture of an organ by computerized reassembling of many bits of X-ray or magnetic wave data, the cytometer creates an image of a cell by sequentially examining tiny sections of it with a laser and then combining the images.
The cell, in effect, is “scanned” through a microscope by the laser beam, and what the laser “sees” at each point in the cell is fed into the computer. The computer can then reconstruct the image on the screen and store the numerical representation for later use.
By using the machine in combination with fluorescent probes, which mimic the actions of certain chemicals, researchers can thus observe exactly how a cell reacts to a certain substance and develop a quantitative analysis of how quickly and how fully a cell absorbs the chemical.
“We can use the quantitative, special information about the cell to see how fast something goes from outside to inside,” Menzel said. Currently, for example, the cytometer is being used to examine how lung cells react to nitric acid, a major air pollutant.
This information by itself would not be all that useful. But it becomes enormously valuable when plugged into computer models which describe the relationship between cell action and the body as a whole, Menzel explained.
“If we know how fast a chemical gets into a cell, and we know how fast it produces an effect, we can write mathematical models based on how the chemical gets into the body--by inhalation, or ingestion, or whatever--and predict how fast the toxic effect will occur.”
Pinning down the relationship between exposure and toxic effect in the body, though, is still only part of the battle. It’s still necessary to determine the relationship between the effect and the incidence of disease.
That’s where rats come in again. By performing the same sequence of tests and computations on rat cells, researchers can produce a specific toxic effect in the animal. Then, the relationship between the effect and the incidence of disease in the rats can be examined.
Finally, after using more mathematical models to compensate for well-understood differences between humans and rats, predictions can be made about what incidence of disease in human beings will be produced by what levels of exposure to chemicals.
Menzel and others involved in toxicology research acknowledge that predictions derived through such tortuous processes are not as good as those based on well-done studies on human beings. And straight animal research still has many adherents.
But in the absence of definitive conclusions based on human experience, predictive data such as that being developed by Menzel will play a growing role in the development of environmental and worker-safety standards, experts agree.
Some of the funding for the Southern Occupational Health Center, in fact, comes from the State Air Resources Board, and the Electric Power Research Institute--an electric-utility group that devotes a lot of resources to air pollution issues--also kicks in some money. The biggest backer for the 100-strong UC Irvine program is the National Institutes of Health.
Money is a serious consideration, since the cytometer alone costs $500,000 and much of the data it collects must be fed into the university’s expensive new supercomputer. But Menzel is convinced that he’s on the right track and that the predictions derived from the research will be invaluable.
“We just can’t wait for 30 or 40 years for people to die--that’s not acceptable anymore,” he said.
