ELISA test marks 35 years of answering medical questions

Washington -- Diagnosing numerous diseases and conditions became a lot easier 35 years ago when a fortuitous melding of research findings led to the enzyme-linked immunosorbent assay, or ELISA test. This simple blood test and its many permutations are now so much a part of the medical landscape, physicians take them for granted.

The uses, of course, include detecting blood clots or allergies as well as pregnancy and infections such as HIV, Lyme disease, H. pylori, chlamydia, rubella, mumps and various rare viruses. The test is also instrumental in ensuring the safety of the nation's blood supply.

Tim Tobolic, MD, a family physician in Byron Center, Mich., orders at least two protein-specific antigen screens each day, not to mention checks for possible strep throats, pregnancies and hepatitis infections. "It's just a simple way of testing for different kinds of proteins and hormones," he said. "It probably plays a big role, and no one ever thinks about it."

Eva Engvall, MD, PhD, a professor at the Burnham Institute, an independent nonprofit research institution in La Jolla, Calif., was beginning her career when the test was developed and often is viewed as one of its inventors.

Dr. Engvall marvels at its popularity. "Now it's everywhere and used for everything." But she balks at the acclaim. "I get too much credit for this so-called discovery," she said. "What I did as a graduate student [working with Dr. Peter Perlmann, professor of immunology at the University of Stockholm in Sweden] was put pieces together that were already out there."

The ELISA test largely replaced the radio immunoassay, or RIA. That test was expensive, required sophisticated equipment and posed safety concerns for lab personnel as well as waste disposal problems because of the radioactive isotopes in the readouts.

A simple test, but yet...

The appeal of the ELISA test and its adaptations lies in the simplicity of the technique, Dr. Engvall said. Dr. Perlmann had the idea of substituting enzymes for the RIA's isotopes. The enzymes served as catalysts for a color reaction instead of a radioactive one.

"I've always in my research aimed to make things simpler rather than complicated," Dr. Engvall said. The new assay soon became accessible to just about everyone, and it wasn't even necessary to have a lab to use it. Giving it an easily recognizable name also helped. "Everyone knew what we were talking about," she said.

Although the researchers suggested a Swedish pharmaceutical firm seek a patent, the company decided against it. Meanwhile, Dutch researchers, unbeknownst to the Stockholm group, were working on a similar test -- the enzyme immunoassay, EIA -- and they did patent it.

"For a while, we were worried that this would prevent people from using the test. But the Dutch team was nice enough to license anybody who wanted to use [it]," she said.

For Dr. Engvall, it is an everyday tool in her Burnham Institute lab. "For everything I've ever done, I've used some kind of ELISA test." She's researching muscle regeneration after discovering a protein primarily expressed in skeletal muscles.

Because the basic ingredients are available, as are standardized ELISA tests for specific diseases and conditions, it can be adapted for use in almost any lab.

Robert Yolken, MD, professor of pediatrics at Johns Hopkins University School of Medicine in Baltimore, was a fellow at the National Institutes of Health when he heard Dr. Engvall give a lecture about the ELISA test nearly 30 years ago. "We decided to apply the test to the measurement of viruses in biological samples, particularly stool samples," he said.

He adapted it to detect the rotavirus, and that application remains in use. It played an instrumental role in the recent Food and Drug Administration approval of a new rotavirus vaccine, Dr. Yolken said.

And he still uses ELISA. "It's a mature technology, but it hasn't changed that much," he said, adding the standardization has helped researchers. "The reproducibility is very good, and they are relatively straightforward."

Dr. Yolken is using the assay to search for infectious agents in neuropsychiatric diseases such as schizophrenia, autism and bipolar disorder.

Others sing the praises of ELISA. "In terms of testing for HIV, it remains one of the most significant tests available to date," said Frenk Guni, director for international affairs and publications at the National Assn. of People with AIDS. "It's also used as a confirmatory test when someone uses the rapid testing kit."

"For us in the blood bank industry, it is still one of the major assays we use to increase blood safety," said Scott Jones, PhD, director of laboratory services at the South Texas Blood and Tissue Center in San Antonio. "For this year, we'll probably do 3 million assays."