Famed Alzheimer's Researcher John Hardy Is a Knight ... but Not in Shining Armor

The celebrated Alzheimer’s Disease researcher John Hardy was among the British doctors and medical researchers honored by Queen Elizabeth II with knighthoods at the dawn of the new year. It was just the latest on a long list of prestigious awards Hardy has collected, including the Potamkin Prize for his work identifying genetic aspects of Alzheimer’s disease, the MetLife Prize, the Thudichum medal, the Robert A. Pritzker Prize, and the Breakthrough Prize.

In 2018, Hardy added the Brain Prize to his list of accolades. Awarded by the Danish Lundbeck Foundation, it is regularly referred to as the “Nobel of neuroscience.” Winners are assumed to be on the short list for the Nobels themselves.

Missing among all the flattering kudos and attendant news coverage has been any mention of the geneticist’s leading role in a conspiracy that held Alzheimer’s research hostage to fraudulently acquired gene patents. The sordid affair mired efforts to find a cure in tangled, resource-sapping litigation. The last of the courthouse wrangling that began in 2003 wouldn’t be resolved for more than a decade – a resolution that came with a ringing rebuke from the bench expressing the judge’s outrage at the scheme, the schemers, and the damage they caused.

Yet until now the full details of the deceptions of Hardy and his accomplices have not been widely reported. Some of them are consigned to scholarly literature and other startling ones are found in overlooked testimony from the prolonged litigation, which documents one of the most celebrated scientists of our time admitting under oath that he lied and committed academic fraud, and confessing that he was ashamed.

The story – which also ensnared one of the world's most prominent woman scientists, who admitted under oath that she too lied, pressured by Hardy – emerges at a time when the credibility of august scientific authorities is being sorely challenged on other fronts, not least during the coronavirus pandemic.

Discontent Was
The Mother of Deception

John Hardy is credited with discovering genetic mutations that suggested Alzheimer’s disease may be caused by an excess of a protein called “amyloid” building up in the brain. His “amyloid cascade hypothesis” has dominated scientific debate on Alzheimer’s for 30 years. It made Hardy famous in scientific circles, and “paved the way for many of the drugs in clinical trials today,” according to the British nonprofit Alzheimer’s Research UK. Among those potential therapies being tested is the anti-amyloid compound aducanumab, approved in the U.S. last summer. Hardy consults with the Japanese pharmaceutical company Eisai, which has brought aducanumab to market under the brand name Aduhelm.

In the glow of what initially appeared to be the drug’s success, media were hardly restrained about the prospects, with the news magazine The Week speculating that the new drug had brought Hardy “significantly closer to a Nobel.”

Overshadowed is the episode that makes Hardy a problematic ambassador for science: In the 1990s he participated in elaborate machinations to misrepresent the authorship of medical discoveries. He led an effort to defraud universities in Britain and the United States of millions of dollars, a scheme that involved empowering a patent “troll” to shake down Alzheimer’s researchers by demanding royalties on bogus gene patents.

Hardy’s dissembling began with a discovery, early in his career, that made his name. “In a leap forward in the search for a cause of Alzheimer’s disease,” the New York Times reported enthusiastically in February 1991, “researchers have discovered that a pinpoint mutation in a single gene can cause this progressive neurological illness.” The Times went so far as to claim a cure could be imminent.

The late 80s and early 90s were banner years for genetic research into the brain. Teams from California, Boston, London, and elsewhere were racing against one another, using new gene-mapping techniques to find the genetic mutation(s) believed to be responsible for early-onset Alzheimer’s. In particular, doctors were searching for the genetic sources of the brain-clogging amyloid plaques and “tau-containing neurofibrillary tangles” found in Alzheimer’s patients.

The publicity – and the suggestion a cure might soon be found – brought pharmaceutical companies to St. Mary’s Hospital at Imperial College London, looking to turn the Hardy team’s findings into therapies. Imperial had an office, Imperial Exploitation Limited (IMPEL), devoted to commercializing faculty discoveries. It operated under the U.K. Patents Act of 1977: In British law, the employer, not the employee, enjoys ownership of any invention created in the “normal course of employment duties.”

IMPEL made a deal with the biotech firm Athena Neurosciences, a bargain Hardy likened to the sort of deal on “Antiques Roadshow” when a hapless seller lets a Rembrandt go for $20. “I was just exasperated,” Hardy would later testify, adding that he “expressed that exasperation in words that would not be suitable for a courtroom.”

That exasperation was shared by some of the doctoral students and post-docs working for Hardy in his lab. Their pique turned to anger when Hardy attended an event at which Athena pitched investors. Hardy said the head of the company bragged he had acquired intellectual property from Imperial College at a fraction of its $10 million value. “I was very angry that we had made such a terrible agreement only two months earlier,” Hardy recounted. “Now here was this CEO saying that the stuff was worth a fortune and that he had paid a pittance.”

Stoking the researchers’ anger was an American businessman, Ronald Sexton, who befriended the Hardy lab crowd, buying them expensive, fancy hotel meals, commiserating with them about how unfair IMPEL had been to them, providing (and paying for) lawyers to represent them, and suggesting ways they could throw wrenches into the Athena deal.

“Mr. Sexton encouraged us to refuse to sign inventor's paperwork and to create other problems for Imperial College and its agreement with Athena,” Hardy said in a sworn statement entered into evidence in a US federal court years later. “Mr. Sexton advised us that by creating problems for Imperial College regarding the Athena Agreement, we could also create problems for Athena and thereby force Imperial College and Athena to renegotiate the Agreement.” Sexton urged Hardy and researchers Michael Mullan and Alison Goate to keep any new breakthroughs on the QT. “Mr. Sexton encouraged us not to disclose to Imperial or Athena any discoveries of additional mutations,” Hardy admitted.

A litigious businessman based in Kansas City, Sexton invested in many things, including gemstones, residential foreclosures, and corporate jets. He had no background in medical research. But he did have an idea for how to monetize the Hardy team’s discoveries: He would set up a company to hold the intellectual property in the form of patents on the mutated genes Hardy’s group had found. Anyone who wanted to do research involving the DNA would be required to pay royalties to Sexton. Hardy and his team would be paid handsomely.

Hardy, Mullan and Sexton devised a plan to scuttle the Athena deal. Mullan, a young medical doctor pursuing a PhD, had joined the Hardy lab in October 1988. What if Mullan had been responsible for key innovations that contributed to the discovery of the London mutation? And what if he had made those advances on his own before joining Hardy’s lab? The case could then be made that Imperial College had no rights to the London mutation because the discovery had been independently made by Mullan before he went to work at the university.

There was a problem with the origin story crediting Mullan. It was phony. Not only would Hardy and Mullan have to deceive Imperial College, they would have to get other young researchers, such as Alison Goate, to lie as well. Nor would these be trivial fibs. It would mean falsifying in writing when and how data was collected and analyzed, a not insignificant act of fraud.

Goate seems a longshot to engage in scientific misconduct. She now chairs the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai hospital in Manhattan. She has been awarded the Khalid Iqbal Lifetime Achievement Award for her work on Alzheimer’s, and she is the founding director of the Loeb Center of Alzheimer’s Disease at Mount Sinai. But in 1992, she was one of the young researchers working for Hardy (and shared one of his accolades). Goate says he pressured her into making blatant misrepresentations of her own lab research.

Goate signed a copy of a letter drafted by Hardy asserting that no work had been done on the London mutation at St. Mary’s, claiming instead that the discovery was Mullan’s. Twenty years later that letter was entered into evidence in a federal civil lawsuit in the Eastern District of Pennsylvania, where Sexton’s intellectual property holding company was trying to enforce patents against Avid Pharmaceuticals and the University of Pennsylvania. “Is this letter a true and accurate description of Dr. Mullan’s role in the discovery of the London Mutation?” she was asked under oath.

“No.” Goate conceded. “It’s revisionist history. It was rewriting and embellishing the events in order to emphasize any role that Dr. Mullan had had while he was not at Imperial College.”

Did she know at the time “that this letter that you signed and sent to your employer in 1992 was in sum and substance false?”

“I did,” Goate admitted. “I am not proud of what I did. I did so unwillingly.” Hardy, Mullan, and Sexton, she testified, pressured her to make the false claims.          

“It was all a lie,” Goate said. “I felt really uncomfortable about telling lies to my employer.” She signed the letter “under duress,” but nonetheless admitted she participated in a “scheme to cheat the Imperial College of London.” RealClearInvestigations contacted Goate and asked her for more details. She replied: “I don’t think my memory of the events that occurred then are strong enough for me to answer your questions beyond the testimony you have.”

When it was Hardy’s turn to be questioned in front of the jury, he expressed little of the remorse that characterized Goate’s testimony. A lawyer pointed him to the key language in a letter he had written to IMPEL: “I can assure you and Athena that none of the work reported in the paper was carried out here at St. Mary’s.”         

“Is that a true statement?” the lawyer asked.

“No.”

“How do you know it’s not true?”

“I know it’s not true,” Hardy said. “I mean, it’s a lie I told.”

The Public Image,
and What Lies Beneath

“As a society we put great trust in science,” Robin Feldman tells RealClearInvestigations. She is a professor of law and director of the Center for Innovation at the University of California’s Hastings College of Law. Scientists who lie about their work, Feldman says, undermine faith in the entire enterprise. Reflecting a general distrust of institutions lately, the public is divided over whether to trust scientists. If a preeminent researcher is found to have lied about his or her work for financial gain it can only fuel a broader skepticism – especially if it is more than just a one-time mistake.

Hardy and Mullan proved willing to make multiple false statements related to genetic patents.

Imperial College didn’t buy Hardy’s myth of Mullan as the inventor, which left Hardy and his team laboring under the terms of the hated agreement with Athena brokered by IMPEL.

If they couldn’t get out of the deal with Athena, Hardy and his team decided, they would not provide the university any more genetic discoveries to be sold at bargain-basement prices. If the university wouldn’t give them the payday they wanted, they would look for a new home for their lab, someplace more generous. In the meantime, they would go on an unannounced sit-down strike. “We decided in the lab to find nothing else that would fall under the agreement,” Hardy testified. “We decided to make sure we didn’t give anything else away.”

The recent history of genetic discoveries in the late 1980s had featured breathless sprints to the finish line, with researchers racing to claim bragging rights as the discoverers – or “inventors” – of the latest scientific breakthroughs. Hardy’s discovery of what became known as “the Swedish Mutation” would feature an odd reversal of that usual practice. Instead of a mad dash to publish his findings, the discoverer of the breakthrough did his best to hide what he had found. And when the discovery was made public, Hardy let it be attributed it to someone else.

In the meantime, John Hardy had decided to get out from under IMPEL’s thumb by moving his lab to the University of South Florida. But the group wasn’t planning to lose valuable months by showing up to an empty Florida laboratory where they would have to start running from a dead stop. And so, in December 1991, Hardy sent Michael Mullan – who had proved his ability to dissemble – ahead to Tampa to start getting things set up.

They didn’t move fast enough. Months later Hardy was still wrapping things up at his London laboratory when a Swedish researcher showed up. Dr. Lars L. Lannfelt had collected genetic material from Swedes with family histories of Alzheimer’s. Hardy had one of his students do a preliminary investigation that showed the exciting – and alarming – possibility that the Swedish samples might produce significant findings. Exciting obviously, but why alarming? Alarming because that would mean Hardy’s team had just made a scientific finding in the London laboratory. Any discovery made there would be, yet again, the property of Imperial College.

Hardy packed up the Swedish samples and mailed them to Mullan in South Florida.

Mullan had the samples sequenced at an independent, off-campus lab. The results spelled jackpot. Significant discovery though it was, Hardy didn’t claim credit. He was still in London and couldn’t be any part of the new finding without IMPEL and Athena taking the intellectual property. Mullan and Hardy decided Mullan would be the one to get the credit. In particular, his would be the name on the patent soon to be filed, giving him exclusive rights to commercial applications and research based on the discovery.

As for the two universities that might have some claim on those rights, Hardy and his disciple had the perfect solution: They kept the University of South Florida in the dark about their most recent discovery – the lab wasn’t even up and running, after all. Hardy and Mullan asked for a waiver on the school’s commercialization rules, claiming they needed some extra time to clear the decks of anything on which Imperial College might make a claim. The University of South Florida’s president of research, George Newkome, credulously signed the waiver, exempting Hardy and Mullan until the beginning of the next semester. They could tell Imperial College that Mullan – who was no longer on the St. Mary’s Hospital payroll –  had discovered the Swedish Mutation in Tampa.

Exploiting
the Swedish Mutation

It was now when businessman Ronald Sexton re-emerged. In May 1992, he incorporated a new business based in Florida, one devoted to commercial applications of the Swedish mutation, the Alzheimer Institute of America. (It is a small measure of how little Sexton knew about Alzheimer’s that the name of his new institute left off the apostrophe-s in Alzheimer’s—an error that was later corrected.) In June, Mullan quietly applied for a patent on the Swedish mutation; as soon as Newkome signed the release for his new employees, Mullan assigned his patent rights to AIA.

Sexton was AIA’s president; Mullan was vice president and treasurer; Hardy remained a silent partner, hiding his role in the genetic discovery. The “Institute” had no infrastructure and did no research. It was what is called, politely, a “non-practicing entity.” Less politely, a “patent troll.”

Non-practicing Entities, or NPEs, “own and sometimes assert patents but do not practice the technology covered by their patents,” according to James Bessen and Michael Meurer, who teach at Boston University School of Law. In a Cornell Law Review essay, they wrote “NPE litigation imposes substantial direct costs on high-tech innovators with little apparent offsetting benefit to inventors or innovators from assertion of NPE patents.”

The discovery of the Swedish mutation was announced in an article in Nature Genetics in 1992. Hardy was not included among the authors of the paper, an article that led researchers to devote years of study to see if the Swedish mutation could be corrected or counteracted in those suffering from Alzheimer’s disease. Strains of mice were bred with the genetic anomaly for laboratory testing. Academics and Big Pharma scientists alike devoted years to the possible treatments promised by understanding how the Swedish mutation worked.

Late in 1995, the first of several Swedish mutation patents Mullan had applied for in 1992 was approved by the United States Patent Office. Sexton promptly began enforcing the patent, demanding researchers pay licensing fees. Many paid the troll’s tolls, but ultimately some refused. AIA sued to enforce its collection of Mullan patents against companies, universities and non-profits, a range of targets from Eli Lilly to the Jackson Laboratory in Maine.

“Patent dispute threatens US Alzheimer’s research,” Nature warned in 2011, declaring that the AIA lawsuit "could expose hundreds of scientists to property-rights litigation.”

And litigation there was, years of it. AIA would bring more lawsuits against more researchers, including academic scientists at top universities such as the University of Pennsylvania.

The extended legal wrangling that followed would ultimately reveal the scheme Hardy had contrived with Sexton and Mullan. But by then Hardy and Mullan had long since fallen out, for reasons that are unsurprising. One day in the spring of 1993, Hardy went to send a fax at the USF lab he shared with Mullan, who had made the mistake of leaving a fax on the machine. “Dear Ted,” Mullan had written a biotech exec. “It was good to meet with you the other day…” Hardy jumped to the conclusion that his partner in hiding the true inventorship of the Swedish Mutation – and who had those patents in his own name – was double-crossing him.

In the middle of the night, Hardy was in the lab emptying the refrigerators of DNA samples that had shown promise. He packaged them up, and in the morning took the boxes to be sent to London. Mullan was tipped off, though, and he told the university Hardy was stealing USF property. The samples, he warned, might be biohazards. The shipment was intercepted.

Comeuppance,
But No Lasting Disgrace

The courts were not kind to the Alzheimer’s Institute of America nor to the researchers who conspired with Sexton and his non-practicing entity. By the time the book was closed on the cases, a jury had rejected the Mullan patents as dishonest and unenforceable. The patent troll was ordered to pay millions in the defendants’ legal fees.

A federal judge was unsparing in excoriating the scientists who had cheated their universities and had hobbled other researchers’ efforts: “The evidence at trial amply showed that Ronald Sexton, AIA’s principal, had conspired with John Hardy and Michael Mullan to defraud USF and Imperial College in London,” pronounced U.S. District Court Judge Timothy Savage. The federal civil jury trial had proved, he said, “that Sexton, Hardy and Mullan conspired to misrepresent the true inventorship of the Swedish mutation inventions in an effort to ensure that ownership of those inventions could not be claimed by Imperial College; and that they intentionally hid the discovery of the mutation from USF to avoid its claiming rights in the invention.”

The judge was just getting warmed up: “On both factual and legal grounds,” AIA’s lawsuits were “objectively unreasonable,” Savage ruled. “The deception, the planning, the execution of the scheme and the motivation of AIA, Sexton, Mullan and Hardy were hardly common or ordinary. Indeed, their conduct was rare and beyond common decency.”

“They were motivated by ego and greed.” Judge Savage concluded, declaring that their effort to enforce what they knew to be phony patents “was nothing more than a perpetuation of the conspiracy,” and an egregious example of “bad faith.”

That bad faith threatened to halt much Alzheimer’s research, and forced scientists and medical institutions to squander valuable resources on expensive litigation. There is “much legal documentation that indicates that [AIA’s lawsuits] imposed enormous costs on the research institutions and private companies it sued,” according to scholars Tania Bubela, Saurabh Vishnubhakat, and Robert Cook-Deegan. “AIA’s contention that it did not hamper research is not credible.”

University of California law professor Feldman tells RealClearInvestigations that it is no accident that patent trolls interfere with efforts to advance science and medicine. Non-productive entities by their very nature siphon away monies that could be funding research: Instead of using patents to encourage the creation of new therapies and pharmaceuticals, according to Feldman patent trolls look to intimidate those who are productive with threats as subtle as old-school protection rackets: Sure is a nice laboratory you’ve got there … Feldman says trolling is as tempting as it is wrong: “We shouldn’t have a system that rewards bad behavior.”

It’s one thing for a non-scientist to use patents to collect tribute from scientists, says Vishnubhakat, a professor of law at Texas A&M University. But it is particularly distressing, he says, that a “legitimate Alzheimer’s researcher” such as Hardy should be mixed up with an NPE. Steven Salzberg suggests the problem isn’t just abuse of patents by trolls, but the very idea of patents on genes. A professor of biomedical engineering at Johns Hopkins University, Salzberg says “I’m against gene patents on scientific discoveries.” Restrictions imposed by patents inhibit free intellectual inquiry, he says.

The Alzheimer’s Institute of America, which once glommed up the work of actual researchers like so much amyloid plaques and tau tangles in the brain, now seems to exist as little more than a long-neglected website, empty but for a dozen broken links.

By contrast, Hardy has flourished. He even fashions himself a stickler for scientific ethics – at least when it is others accused of impropriety. David Latchman, another genetics professor at University College London, had been under investigation for falsified data. Inquiries over several years found there had been research fraud in Latchman’s lab, but that the misconduct was committed by “junior lab staff.” Hardy declared himself angry that Latchman wasn’t fired: “Some minion carries the can. This is how it is, all the time. The powerful get away with it,” he said. Latchman “has to take responsibility,” Hardy told London’s Observer newspaper two years ago. “He should be fired by UCL because he was leading a lab that published systematically fraudulent science.”

RealClearInvestigations asked Hardy in writing whether that same standard should apply to him, given that not only did he dissemble about his own work, he pressured his lab staff to make false statements about their research. He did not respond. Written questions were also submitted to Michael Mullan. He did not respond. Nor did former USF official George Newkome. RealClearInvestigations reached out to several lawyers who had represented Sexton, but without success.

How is it that Hardy’s fame within the scientific community has grown over the last three decades, even though he has admitted to lying about his research? It may be because, until now, those admissions have gone unreported. Scientists can’t be expected to know about admissions of wrongdoing buried in court records. But before hanging more medals on Dr. Hardy, the scientific establishment might have looked into the allegations about Hardy made in a careful academic article “The Mouse That Trolled,” published in 2015 in the scholarly Journal of Law and the Biosciences.

Hardy brushed those criticisms aside, writing that “hindsight is always 20/20 vision” and that the “saga [was] in our rear-view mirror.”

Hardy was not nearly as nonchalant three years earlier when he was on the witness stand, facing a federal jury. At first, he indulged in what he himself described as “wisecracks.” But the man who may yet be honored with a Nobel prize eventually admitted the seriousness of his wrongdoing:

“Science is all about telling the truth, and this is really a blot on my career,” Hardy said. “I know why I did things. I know what was my motivation, but didn’t follow a golden rule, which is when you are in a hole, stop digging. And I just kept digging and getting deeper and deeper and deeper. And you know, I’m not happy about – I’m not happy about it. I’m ashamed of it. I’m ashamed of it.”