Fel d 1, which is unique to cats, is responsible for most people's allergic reactions to cats. 2 Still, little is known about the protein and Allerca's findings could lend insight into the unknown function of Fel d 1 in cats, says Leslie Lyons, assistant professor at the UC-Davis School of Veterinary Medicine. "We're interested in pursuing this stuff a little farther," she says, but "they don't present enough data to say how they've done it."
Lyons isn't the only one scratching her head over the lack of peer review of Allerca's claims. "There's a lot of skepticism in the academic community about whether or not these cats are hypoallergenic," says Martin Chapman, a former professor of Medicine and Microbiology at the University of Virginia and the founder of Indoor Biotechnologies, a company that designs allergy tests. "We've not come across any documented scientific study that this is...
Compounding the scientific skepticism are the many failed and sometimes-fraudulent business endeavors of Allerca's founder and chairman, a convicted criminal named Simon Brodie. Hot air balloons, glow-in-the-dark deer, the world's most powerful computer, and knockout, allergen-free cats have all collapsed despite Brodie's public optimism and legal issues often trail behind these entrepreneurial efforts.
In June 2006 an Allerca press release announced that customers could begin reserving their hypoallergenic cats. Less than a year earlier Allerca's scientists (whose identities have been kept under wraps) stumbled upon a family of hypoallergenic cats while testing out the company's newly developed genetic assay, says Brodie. He explains that the researchers were screening cats randomly across the country for the initial project to develop allergen-free cats using RNAi. "The test was initially to look for the fel d 1 gene," Brodie says, "and it was not found positive for the mutant cats. We did additional work ... and found the molecular weight of the protein was different in the mutant cats." Brodie declines to say more about how the assay was developed or precisely what it is designed to detect in the cats.
Allerca hired Microbac, a commercial laboratory in Tennessee, to compare the fel d 1 sequences between Allerca's cats and control cats. Robert Brooks, then the biotechnology laboratory manager at Microbac, conducted the analysis in May, June, and July 2006. Allerca provided Brooks with cheek swabs from several parent cats, and later from several kittens. Brooks used the DNA to compare amino acid sequences between Allerca and control cats.
Fel d 1 comprises two subunits, each encoded by a different gene. 3 In chain 2 Brooks found several amino-acid differences in Fel d 1 between Allerca cats and control cats, which have not been documented in the literature. "Every Allerca cat had those," Brooks says. He would not disclose the differences, saying that the information is proprietary. He did not sample the actual cats, nor did he do any work with Fel d 1 to see how changes in the sequence might affect the hypoallergenicity of Allerca's cats. "I don't have anything to do with cats themselves," Brooks says. "There are definite differences [in their protein]; what they mean, I can't tell you."
Brodie says Allerca's researchers (not Microbac's) discovered that these differences translate into cats that don't elicit allergic responses in people. Allerca's team also found the trait was passed along to offspring, and began breeding the hypoallergenic cats in the fall of 2005 to "allow allergic consumers to enjoy the love and companionship of a pet without the cost, inconvenience, risk, and limited effectiveness of current feline allergy treatments."
Such a finding is feasible, says Lyons. There could be enough variation in the fel d 1 gene in the domestic cat population (about 30 million in the United States) to allow for a hypoallergenic mutation to exist, she says. Others have shown it's feasible at the molecular level as well. Modifying a recombinant Fel d 1 to destabilize the protein can result in hypoallergenicity. Hans Gr??nlund at the Karolinska Institutet Hospital in Stockholm and his colleagues showed that modifying the three-dimensional structure of Fel d 1 could reduce its IgE antibody-binding capacity 400 to 900 times that of an unaltered Fel d 1. 4 Gr??nlund writes in an E-mail that it's impossible to speculate on what mutations might be responsible for the Allerca cats' hypoallergenicity, though "probably a deletion or several point mutations would be needed."
"There's a lot of skepticism in the academic community about whether or not these cats are hypoallergenic." -Martin Chapman
Lyons says that demonstrating a mutant fel d 1 gene in certain cats would be easy, as several studies have described the gene and protein. Characterizing the way humans will respond to the animals, and showing that they really are hypoallergenic, would be more difficult. Lyons says she doesn't have many doubts as to whether Allerca could have found cats with a mutant Fel d 1. "For me, the question is, how are they proving it?"
That's where Sheldon Spector comes in. An allergist with the California Allergy and Asthma Group in Los Angeles, he conducted Allerca's human exposure trial earlier in the year. (Spector declined to be interviewed until after his second round of trials was complete, which an Allerca spokesperson estimated would be in late November. As of press time, Spector had not responded to further requests.) For his first trials Spector used three rooms, each randomly housing a hypoallergenic cat, a regular cat, or a stuffed animal. Volunteers who had been diagnosed with allergies entered the room blindfolded and reported their allergic responses. Spector found the hypoallergenic cats did not elicit an allergic response, though he has not published the results in a peer-reviewed journal.
Using this experimental design is not always a reliable predictor for hypoallergenicity, says Andy Saxon at the UCLA Medical Center: "It's a mess using cat rooms; they're totally uncontrolled." Saxon says several problems exist with cat rooms: The amount of allergen a person is exposed to is not controlled, and a person's response (even to the same amount of allergen) can vary with each exposure. Even Spector told The New York Times in October that he would not recommend people buy an Allerca cat, because his study was not definitive and people can still react to other allergens that cats produce.
Sensitization also plays a role. "If you eliminate only part of the protein, you may develop sensitization to a different part," says Fernando Martinez, director of the Arizona Respiratory Center. Martinez says that the number of epitopes humans respond to on Fel d 1 is not well known, and sensitization to particular areas of the protein has not been explored exhaustively. "I would argue that there are essentially unlimited number of epitopes," writes Gr??nlund. As the oldest generation of Allerca cats is just three years old, there is no evidence that they will maintain their hypoallergenicity for pet owners over a lifetime. The lack of a published peer-reviewed trial concerns a skeptical Martinez. "It's very worrisome that before there's any demonstration of a true effect, we start giving these [cats] to people," he says.
In 1992, Brodie was a young, Lamborghini-driving man of 29, working out of plush offices in London and renting a large home. He had launched a hot-air ballooning company called Cloudhoppers, which, according to news reports in 1992 by British newspaper The Argus, grossed ??1 million in its first year and had ambitions for expanding to a ??50 million enterprise stateside. It was advertised as the largest ballooning company in the world, but after Brodie announced that the company was going to be bought for ??4 million, his success collapsed.
Reporter Richard Fleury of The Argus conducted an investigation that exposed a number of lies and ultimately resulted in a jail sentence for Brodie. Not only did the ??4 million deal never take place, "We discovered Cloudhoppers owned just two balloons and had been running up sky-high debts for months," reported The Argus in 1994. "The firm was continuing to take bookings for expensive balloon flights even after the Civil Aviation Authority revoked its license to fly." The Lamborghini was repossessed, the offices abandoned, and employees were not paid. According to published reports, Brodie was sentenced to two-and-a-half years in jail after pleading guilty to multiple counts of false accounting.
Brodie's legal troubles followed him to the United States. Olympic Avenue, where Allerca had its official headquarters, dead-ends behind the Santa Monica County Building. Court records inside the low, white building reveal Brodie has been sued a number of times in the Los Angeles Superior Court for contractual fraud, eviction, and unpaid debt. A 2004 case shows Brodie was using an alias, Simon Campbell, and was connected with Cerentis Corporation and Integra Associates. Cerentis' goal in 1999 was to develop the world's largest supercomputer by linking together 10,000 PCs with a downloaded screensaver called Terra One, according to a press release. The project never saw completion, or perhaps never even began.
Similarly, one of Brodie's former companies, Geneticas, claimed it would provide customers an allergy-free cat based on RNAi and had already accepted hundreds of nonrefundable $250 deposits. Geneticas also predicted it could bring the cost of cloning a cat below $10,000. The cats never came and Geneticas disappeared (see "5 Cat allergen is one of the most common allergens, found in nearly all US homes. 6 )
"That's when I came up with the idea for genetic modifications to make an allergy-free cat," says Avner. "I said, why don't we just turn off the gene that makes the allergen altogether?" But to launch his idea, Avner would need financial backing.
"It's very worrisome that before there's any demonstration of a true effect, we start giving these cats to people."
According to Avner, Simon Brodie approached him with a deal: Avner would set up a lab and Brodie would provide the capital. In 2004 the two men agreed to set up a company called Allerca and start working on knocking out a gene for Fel d 1. But before the first gene could be silenced, Brodie pulled out of the deal. "Within two weeks he basically took everything and claimed it was his own," says Avner. "He took all of our business plans, marketing, and filed his own papers to create his own company with the same name and everything."
On October 26, 2004, Brodie incorporated Allerca with the California Secretary of State, and shortly after that, Avner took Brodie to court. The judge ruled in Avner's favor, and enjoined Brodie from developing and marketing Fel d 1 knockout cats until May 31, 2006. But, Brodie claimed to have found an easier way to produce hypoallergenic cats. One week after the injunction lifted, Allerca distributed a press release that the company was able to selectively breed, not clone, cats that don't stimulate the human immune system.
Avner says he thinks it's all a scam. "I don't believe they exist," says Avner, who is still seeking funding to launch his allergen-free cat research. "It's not a grudge. Their science is unsupported. Their claims are unsupported."
Brodie says not to expect any peer-reviewed papers or patents on Allerca's discoveries. His reasons are twofold. "Coca-Cola doesn't publish its secret recipe," he explains. With interested customers in 85 countries, Brodie says he wants to protect the international market and keep the information on the cats' mutation and their screening process proprietary. "We have something special here and we want to keep it confidential." Brodie's other reason stems from the death threats Allerca says it receives each week from animal activists. "Our biggest concern is security. ... The more intelligent people out there realize it's dangerous [work]."
Brodie says he understands there are doubters, particularly in the scientific community. But with the first round of kittens planned for delivery in the next several months, Brodie says the truth about the cats will become apparent. "The proof is going to be that customers [with allergies] will have these cats and will be living with them. And that is the proof. We can provide every piece of scientific evidence and there will still be doubt."
UCLA's Saxon sees only one reason why Allerca should keep data from the public. "If they haven't published, why? Because it didn't work?" he asks. "I'm all for a hypoallergenic cat, but I'm not buying one yet."