It's the time of year when mysteries, legends and myths run rampant. Spooky stories are great for around the campfire, but when mystery and myth surround an institute year round, rumors and legends become truths. The Wistar Institute is known for the myths surrounding it, from unknown subterranean levels and tunnels to collections of brains and aliens.
Wistar originated as an anatomical museum, and it does still have brains and other odd specimens dating back to its founding. There are ashes of previous directors in large metallic urns with their names engraved on the sides. They fill a showcase in one of Wistar's halls and the effect is completed with oddly lifelike petrified trees on display underneath them. There's even a matching brain somewhere in the basement to accompany the ashes in one of the urns. But there is only one underground level to this research institute, and there are no mad scientists -- just people who seem slightly obsessed with their work. Despite its antiquated appearance from the outside, the inside of Wistar is modern, from the flat screen computers to the new technology used for research.
Wistar is not affiliated with the University of Pennsylvania. It is the oldest independent private research institute in the United States, founded in 1892. It has its own labs and buildings; it has its own endowments and board of trustees. Wistar doesn't get much through traffic of students, or anyone else for that matter. With so few students going into Wistar, no classes going on inside Wistar, no customers and no patients, those on the outside can only speculate about what happens in Wistar, an image that the institute is trying to shed.
Wistar has begun a free film series, intending to entice skeptics into the institute to see what it's really like. Called "Biology in the Movies," Wistar is hosting movies like 12 Monkeys, Gattaca, Frankenstein and Jurassic Park. While there may not be tremendous similarities between the movies and what happens at Wistar, the point is to get people interested in Wistar and science and to introduce them to what Wistar really is. Wistar is trying to negate some of the false rumors through good publicity, but the battle is tough when the fight is against many years of false impressions.
One of the most unsettling stories that includes Wistar concerns its involvement in the September 1999 death of Jesse Gelsinger. Dr. James Wilson, who -- with the help of Penn -- was leasing a space from Wistar, was the doctor working with Gelsinger when he died. Wilson was actually the director of Penn's Institute for Human Gene Therapy, and a member of the Wistar faculty only by secondary appointment. Since there's no affiliation between the two institutions, Wistar wasn't involved at all in the tragedy. Wistar, in fact, does not have a human clinical testing department. It has nothing to do with human testing at all. The scientists at Wistar mainly work with mice and rats. When research seems viable to test on humans, Wistar must partner with places like HUP to get those kinds of trials done. However, Wilson does collaborate to this day with one of Wistar's scientists, Dr. Hildegund Ertl. His expertise in gene therapy works well with Ertl's immunological knowledge and together they try to construct vaccines and platforms for them. When asked how she felt about Dr. Wilson and the Gelsinger mistake, she said, "He wasn't the only one who was doing it. There were dozens of clinical trials ongoing. He just had really bad luck, getting a kid that had an unusual response; it could have happened to others but it happened to him." Some other responses weren't as positive. A Washington Post article written by Justin Gillis in June of 2002 asserted that Dr. Wilson "had a direct financial interest" and that "Wilson and other doctors had ignored serious danger signals when they proceeded with the test that killed Gelsinger." Ertl said, though, "he's a very smart guy with a lot to offer to science." Together, the two work on vaccines for HIV, rabies, and agents of bio-warfare for National Institute of Health, which is government owned.
In 1992, Rolling Stone ran an article called "The Origin of AIDS" by Tom Curtis. In it, he questioned whether the polio vaccines that were provided by Wistar and were given in clinical trials in the Congo in the 1950's were contaminated with HIV. In 2000, a book called The River: A Journey Back to the Source of HIV and AIDS, by Edward Hooper, picked up on some of the ideas that had been sketched by Curtis. He hypothesized that the vaccines became infected when Wistar used chimp cells to prepare the vaccines. Chimpanzees harbor a similar virus to HIV called SIV (simian immuno deficiency) that most scientists believe jumped species to become a mutant strain that we now know as HIV. The Congo, where the vaccines were extensively used, was also the area that HIV is thought to originate from. Wistar cooperated with the investigation of their polio vaccine. Eventually, it was discovered that Wistar prepared the vaccines using rhesus monkeys, not chimpanzees. Rhesus monkeys, unlike chimps, do not harbor HIV or SIV. The saved polio vaccines were also tested and came back negative for SIV, HIV or any chimp DNA. The repercussions of this, however, still haven't passed. In the past week it's been reported by the Australian Broadcasting Company that the World Health Organization's attempts to immunize against another growing outbreak of polio in Africa was halted by officials in northern Nigeria. The officials believe that the vaccines are contaminated "either by accident or design."
Aside from the drama, Wistar's main focus, about 90 percent of its efforts, is geared in some way towards cancer. Research revolves around how genes are structured and controlled, how they control normal and abnormal development, why they go awry and how cancers are formed. The rest of Wistar deals with research of vaccines for things such as HIV and SARS.
In a world of Wal-Marts, Wistar is rather small. It is one of the first nationally funded cancer centers and one of only eight basic research institutes that are cancer centers. One reason for Wistar's success is its location on Penn's campus. Many of the negatives associated with smaller programs like Wistar are alleviated by the mutually beneficial relationship between the University of Pennsylvania and the Wistar Institute. Many of the scientists at Wistar also have faculty appointments at Penn, and about 30 graduate students are trained at Wistar's labs each year and earn their degree from Penn. Many scientists at Wistar and Penn work together on research projects, and since one institution doesn't have to report to the other, the relationship between the two is seen as a collegial one. Many Penn and Wistar scientists work together and even share grants for the research that they perform together, as is the case with Wilson and Ertl.
One scientist, Dr. Louise Showe, has worked at Penn and the Children's Hospital, and is now at Wistar. She says she "likes the small setting and not having to deal with all of the red tape involved with the big university departments," but regrets that her shift from a big operation to a smaller one has meant that she's had to sacrifice the tenure that Penn provided. Not having tenure means that the scientists have to support themselves by living off of soft money, which means to keep working the scientists have to keep getting grants from places like the National Cancer Institute. Ertl agrees. "Fluctuations in the economy very much affect our ability to obtain funding either from federal sources or philanthropy," a worry that larger institutions like Penn don't have to worry as much about.
Showe's research uses the "big picture approach" to view cancer by comparing healthy and unhealthy samples to see which genes are different. Instead of focusing on only one or two genes, she tries to look at as many genes as possible to find discrepancies. The technology that Showe uses to do this is new and high tech. She's "always been interested in new technology." The instrument she uses is called a DNA microarray. Wistar is only one of a few institutes that has its own microarray facility. This is the first part of a two part process. By looking at the expression patterns of the genes, Showe finds out which genes are involved to get clues to develop hypotheses that can be tested on more focused levels - the usual approach. By using these methods hand in hand, diagnoses can be faster and more specific to each person and their genes and cells. She likens it to "fishing with a really big net," a less conventional method than the hypothesis method which most scientists work with. Because her research is unusual and promising, Showe has been lucky enough to become one of 10 investigators to receive a grant from the National Cancer Institute for five years and a three year grant from the Commonwealth of Pennsylvania, among others. The purpose of the National Cancer Institute's grant was to develop this new array diagnostic tool which isn't limited to one cancer, but for many different cancers. The grant, and Wistar's interest in having the technology, helped Showe decide to change directions completely from her earlier work. She has also collaborated with Penn's Alain Rook from the department of dermatology for the past six or seven years on this project. Even though he's from Penn and she's from Wistar, Showe "doesn't really think of us as competitors because we're working on different systems," though using the same technology. Showe credits Wistar's small infrastructure for allowing her to follow new technology in a different direction than she had been taking previously. She was able to speak immediately to the director, who could give her an answer rapidly and without much paperwork and other management interference.
Showe is also an adjunct member of the dermatology department and teaches undergraduates in her labs in a hands-on environment. When she first set up the facility of arrays at Wistar she couldn't hire full time employees, so she hired four Penn students. Two were bioengineers and two were incoming freshman who were so interested in the project that they applied even before they arrived at Penn. She worked with them for all four years that they were at the university and got to know them better than almost any teacher could know a student since they were working together almost everyday.
Wistar's employees are satisfied with its size and personality. As in Showe's case, the administration and size of Wistar allows for change if a scientist discovers something interesting not directly pertaining to the field they were working on. Instead of going through levels of chain of command and filling out extensive paperwork, scientists head straight to director Kaufman for approval. There's no holding on the phone and no elevator music. This means that turn-around is faster, experimentation is faster, results are faster, and the help of the research gets to those who need it faster. Even the staff of Wistar is of a dying breed - they actually know each other. Everyone in Wistar seems to know everyone else. The guards and the support staff know the scientists personally and know what projects everyone is working on. Ertl says, "I know everyone at this institute, so if I need something done, be it something as trivial as getting something fixed in my lab, I can go to physical plant and say 'Hey John, can you fix it now?' and he'll come upstairs within ten minutes and I'll get it done."
While Wistar looks to the future, it also embraces the past and its ideals and dedication that have been passed on. The institute was named after Casper Wistar, who was known as the first great American anatomist. He was also a physician who began his medical practice in 1787. He lived in Philadelphia during the time of Benjamin Franklin and was friends with Thomas Jefferson. He wrote the first American anatomy textbook and taught anatomy. He collected around 20,000 anatomical specimens to be used as a teaching aid, some very unusual. After Casper's death, his nephew Isaac wanted to honor his uncle's memory and collection by continuing the study of anatomy as well as biological research, but in 1888, a fire damaged part of his collection. The Wistar Institute was built in 1892 and housed all of Casper's specimens that survived the fire. About ten years after it was founded, the director of the institute started contacting scientists from around the world to come to his research institute where the focus was then on embryology, genetics and neural development. The anatomical museum rapidly transformed into a research institute. This tradition continues today. Wistar calls labs the world over and asks about their best post-docs who are leaving. They then ask those post-docs to visit Wistar in hopes that the very things about Wistar that make it special to those who work there -- size, interactive environment, shared facilities within one building -- will entice the scientists to call Wistar their home, too.
Another part of Wistar's past that has now spread around the world is the WISTARAT, the first standardized laboratory animal. Even though the project was begun in 1906, it is thought that around half of all laboratory rats today are descendants of the original WISTARAT. Some of the scientists at Wistar tried breeding more docile rats by picking the tamest rats and breeding them repeatedly. From the mildest group of black and grey rats, a breed of white, extremely docile rats evolved. It was a tame mutant perfect for use in experiments because of their sweet nature. Although most laboratories use mice now because they're smaller, eat less, have a shorter gestation and require less space, the WISTARAT is still the more docile option.
Science, its possibilities and the unknown will always be something of a mystery. Some things about Wistar are still a bit creepy and probably always will be. It's the nature of the institute and of science itself. But Wistar is moving forward with scientists like Showe and Ertl who are trying to figure out some of those mysteries of science to help the future.
Photos by Ryan Jones
