San DiegoNeuroscientists who use mouse models areclosely watching a patent infringement bat-tle between a prominent biotechnologyfirm and a major US non-profit institution.

Elan Pharmaceuticals, of Ireland, is suingthe Minnesota-based Mayo Foundation forMedical Education and Research over miceused to study Alzheimer’s disease. The com-pany alleges that Mayo has infringed twopatents it holds on transgenic mice with amutation that causes Alzheimer’s.

Elan uses its closely guarded mice forwork on potential drugs against the neuro-degenerative disease. The company allegesthat Mayo is infringing its patents by making,using, and selling mice that overexpress anAlzheimer amyloid precursor protein,APP695, from a human genetic mutation.Mayo says it has licences from patent holdersfor both the mutation and the mice, which itdistributes to researchers worldwide. A juryis due to decide the issue in October.

According to documents filed with theUS District Court in San Francisco, Mayo ismaking the counterclaim that the Elanpatents were obtained fraudulently from theUS Patent and Trademark Office and thatthey are unenforceable and therefore invalid.Mayo attorney Karen Boyd would not speci-fy the grounds for such allegations.

The battle is spreading unease among USneuroscientists because some are being sub-poenaed — along with their laboratory note-books — to testify in depositions for the civillawsuit quietly filed by Elan last April.

“It is outrageous,” says Karen Duff, a NewYork University neuroscientist who has beensubpoenaed by Elan. After receiving her doc-torate at Imperial College London, Duffonce worked at Mayo’s research facility inJacksonville, Florida, and has used the Mayomouse model to create another transgenicmouse that is considered extremely impor-tant for research.

The dispute is seen by neuroscientists ascomplicating an already difficult researcharena, in which the number of animal mod-els for unravelling the biological secrets ofthe disease is already limited.

“All of this does no one any good,” says

John Trojanowski, a physician with a doctor-ate in neuroscience who directs a NationalInstitute of Aging (NIA) Alzheimer Center atthe University of Pennsylvania. “TheAlzheimer research field could move consid-erably faster” without the lawsuit, he argues.

In December 1998,as the Elan–Mayo dis-pute was heating up,NIA officials held aprivate two-day work-shop of neuroscientiststo address problemsassociated with Alz-heimer’s research usingtransgenic rodents.Although Mayo andElan subsequently helddiscussions about re-

solving their dispute out of court, Elan filedits lawsuit a few months later.

Elan attorney Jean Duvall says that no oneat the firm’s Dublin headquarters will com-ment except to say “it is Elan’s policy toenforce its intellectual property rights”.

The Elan–Mayo lawsuit is so sensitivethat Marcelle Morrison-Bogorad, NIA’s

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associate director for neuroscience and neuropsychology, cancelled a scheduledinterview on the subject last week — shortlyafter the joint statement by President BillClinton and British Prime Minister TonyBlair on the need for open access to geneticdata (see page 324).

“It is critically important that researchtools are available to scientists,” Morrison-Bogorad says. “We are looking into the cur-rent controversy over research resources forAlzheimer’s disease and evaluating its impacton the field, on initiatives in the private sec-tor and on the overall progress of research.”

The Elan–Mayo legal dispute involves anumber of patent, licensing and researchagreements with both proprietary and acad-emic institutions. The two patents Elanalleges are being infringed are owned jointlyby the firm and Eli Lilly & Co.

Elan secured rights to the patents in 1998,after acquiring Athena Neurosciences, a firmthat had licensed research findings from aca-demic institutions and companies.

The two Elan patents are for “transgenic …rodents” that harbour an allele for the‘Swedish mutation’ — named after a large

Researchers caught in disputeover transgenic mice patents

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MunichRadioastronomers may not be gloatingpublicly over the final plunge of the globalmobile telephone company Iridium intobankruptcy last week. But news that thecompany’s 66 satellites must be brought outof orbit and burnt up in the atmosphere aspart of the bankruptcy agreement hasignited a private outbreak of schadenfreude.

Radioastronomers have been fighting foryears against the satellite system developedby Iridium, which was allocated a wavebandright beside the 1612 MHz band reserved forastronomical observations. Despiteassurances, Iridium refused to cap the use ofits satellites at a level that would avoid‘overspill’ into the radioastronomy band,drowning out weak radio signals from space.

Last year, European radioastronomersreached a compromise with Iridium underwhich the company was required toguarantee some hours of ‘quiet time’ overradio observatories (Nature 399, 513; 1999).But since their launch in November 1998,the 66 brightly reflecting satellites have alsointerfered with optical observations fromground-based telescopes.

“We have learnt from the affair thatpromises made at one time are not alwayskept,” says Willem Baan, director of theWesterbork Observatory in northernHolland and one of the fiercest opponents of Iridium. Been is now working to ensurethat, in future, frequencies reserved forscience are protected from unexpectedcommercial encroachment. Alison Abbott

Iridium crash relieves astronomers

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Younkin: licensingagreement necessary.

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is handled, with just a few people makingdecisions for the rest of us.” The Internet, headds, “could allow us to hold large ‘townmeetings,’ where many people voice theiropinions and, in the end, a vote is taken”.

Several respondents, though, argued thatnominations should not be aired in public.

Meanwhile, Haym Benaroya of Rutgerswas anxious to avert an e-mail meltdown,and urged people to stop sending messagesto the Rutgers list. “At one point, I wasgetting 10 to 15 e-mails every 10 minutes,”he says. “With everybody talking to every-body else, things were snowballing. Thewhole system could have been shut down.”

The snafu was corrected within a day,and an apology issued. Future nominationswere requested by post, rather than e-mail.

The apology put an official end to theepisode. But Shapir hopes that an importantlesson might still be learned. As a result ofthe computer glitch, he says, “for a briefperiod of time, we got a glimpse of howthings could be done. We don’t have to clingto the secretive ways of the past.” Steve Nadis

be awarded in Mexico, in summer 2001.)Recipients were meant to reply to him alone,not sending their comments to each other.

Juerg Froehlich of EidgenössischeTechnische Hochschule Zurich nominatedJohn Cardy of Oxford University, also citingthe work of Sasha Zamolodchikov ofRutgers. “But something went wrong,” saysLebowitz. “The computer went haywire”when Froehlich hit the ‘reply’ button, andhis suggestions went to all 3,500 on the list.

Others soon joined in the nominationfrenzy. Roger Bidaux of the Centre d’Etudesde Saclay in France advanced the name ofLawrence Schulman, a physicist at ClarksonUniversity in Potsdam, New York. “I believethat our community can afford a little bit oftolerance and democracy, and allow me toexpress my opinion,” wrote Bidaux.

University of Rochester physicistYonathan Shapir shared this sentiment,saying he’d like to see the process conductedin a more open, democratic fashion.

“There is a lot of secrecy in academia,”says Shapir. “I don’t like the way this business

BostonThe normally tranquil world of statisticalphysics and mechanics was rocked last weekby a computer glitch that led to a flurry ofexchanges over nominations for the field’smost prestigious prize, the BoltzmannMedal. The prize is awarded by theInternational Union of Pure and AppliedPhysics (IUPAP) once every three years.

The glitch triggered a debate betweenthose who regarded the proliferating e-mailmessages as a nuisance that threatened tooverwhelm computer networks, and otherswho welcomed an unaccustomed openness.

The source of the problem was the 3,500-strong mailing list kept by the Center forMathematical Sciences Research at RutgersUniversity, which hosts two conferences onstatistical mechanics each year.

Kurt Binder of the University of Mainz inGermany, who chairs the IUPAP committeethat issues the Boltzmann Medal, asked JoelLebowitz — a member of the nominatingcommittee — to send an announcementsoliciting nominations. (The next prize will

Scandinavian family in which it was identi-fied — that is believed to contribute toAlzheimer’s disease by producing a build-upof amyloid plaque in the brain.

Researchers say that Elan transgenic miceare closely held by the firm for its drug devel-opment efforts. One researcher alleges thatwhen Elan mice are provided to academicscientists, they are usually neutered females.

Mayo’s transgenic mice, provided tomore than 50 academic research groups anda dozen pharmaceutical firms, are based onwork by a group headed by Karen Hsiao atthe University of Minnesota.

Hsiao’s group created a mouse that wouldexpress amyloid in the brain (see Science 274,99–103; 1996). After publication, Mayolicensed the discovery from the University ofMinnesota, arranged for contract breedingof the mice and began distributing them.Mayo also licensed the sequence of theSwedish mutation from a Kansas firm.

Mayo’s mice are considered so valuablethat there are reports of breeding trios ofmales being sold to companies for $850,000.Mayo officials decline to discuss this.

When providing its mice to academicinstitutions, Mayo requires the signing of amaterial transfer agreement that gives thenon-profit organization an option to buy therights to any commercial discovery that maycome from research with the mice.

This agreement — like those used bybiotech firms — is considered by some to bean unusually bold move for a non-profitorganization. Even some of Mayo’s own

researchers have difficulty with this practice.“My view is there should be no reach-

through agreements between non-profitinstitutes,” says pharmacology professorJohn Hardy at Mayo’s Jacksonville facility,whose laboratories at Imperial College Lon-don, South Florida and Mayo have producedleading discoveries and researchers.

But Steven Younkin, a physician neuro-scientist and former director of research atMayo’s Jacksonville facility, defends theagreements as being necessary to cover theorganization’s enormous cost for the long-term, mouse-producing project. “With anon-profit institution such as Mayo, anymoney realized from licensing agreementsgoes back into research,” says Younkin.

If Mayo was primarily interested in mak-ing money, he adds, it would have entered anexclusive licensing agreement for the trans-genic mice with a single pharmaceutical

firm. It deliberately decided not to do this,in order to make the mice available foracademic research.

As neuroscientists debate these issues,subpoenas have been spreading throughthe neuroscience community. Earlier thismonth, Elan failed in a bid to requireHsiao to produce her laboratory note-books for a deposition this week.

A number of researchers, includingmicrobiologist David Borchelt, an associ-ate professor of pathology at Johns Hop-kins University in Maryland, are debatingtheir options as they face subpoenas.Unable to secure the desired transgenicmice, Borchelt made his own mice.

Elan has now subpoenaed him and hislab notebooks, which he fears may bestudied closely by the firm’s scientists.Borchelt says he would “go to jail” ratherthan provide his notebooks. Rex Dalton

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Computer glitch unleashes prize nomination debate

Mice work: the brainof Elan’s one-year-oldmouse (far left) showscharacteristic plaquesof Alzheimer’s disease,absent from that of thesimilar animal (left),which was dosed withElan’s experimentalAlzheimer’s vaccine.

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