Science on the Sly

A scientist at the University of Kansas Medical Center, Kansas City, Kans., pleaded guilty in May in a case involving theft of research materials from the Cleveland Clinic Foundation in Ohio. In a plea bargain with prosecutors, Hiroaki Serizawa, an assistant professor of biochemistry at KUMC, admitted he lied to FBI agents who were investigating the theft of DNA, cell line reagents, and other genetic research materials used in Alzheimer research at the Cleveland Clinic. Officials say that the 19

By Ted Agres | June 10, 2002

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Okamoto had been researching Alzheimer disease at the Cleveland Clinic from January 1997 to July 1999, when he abruptly resigned. According to a federal indictment, Okamoto stole several hundred vials containing cell line reagents and DNA samples, destroyed remaining materials and lab notes, and left behind mislabeled vials filled with tap water. Okamoto then shipped the stolen DNA and reagents to Serizawa for safekeeping.

In August, Okamoto retrieved the purloined materials from Serizawa and took them to the Institute of Physical and Chemical Research (RIKEN), a facility near Tokyo funded largely by the Japanese government and at which he had recently obtained a position as a neuroscience researcher. Okamoto has been charged with economic espionage, altering and destroying trade secrets, and interstate and international transfer of stolen materials. The Justice Department's request for Okamoto's extradition to face trial in the United States "is under consideration by the government of Japan," says Chris Strickan, assistant US attorney in Cleveland.

Courtesy of Mark Frankel

Mark Frankel

Theft and misappropriation of research materials from life sciences laboratories is becoming "more problematic as science gets bigger, as more things are produced, and people leave to pursue things independently," says Mark Frankel, director of the Scientific Freedom, Responsibility, and Law Program at the American Association for the Advancement of Science (AAAS). Unfortunately, no one has a good handle on the amount of theft or misappropriation from labs because records are not kept consistently.

It is clear that the economic value of research is exploding, with billions of dollars in new drugs, therapies, and other discoveries at stake. The commercialization of US academic research annually results in more than $40 billion in economic activity, according to the Association of University Technology Managers. Nearly 12,000 new discoveries were disclosed in 2000; more than 9,500 new US patent applications were filed; and approximately 3,600 patents were issued to US universities, medical schools, and research institutions.¹

"Obviously, with congressional legislation encouraging commercialization of scientific ideas, there's been a lot more emphasis on the financial side of research," says Chris Pascal, director of the Office of Research Integrity (ORI), the watchdog group at the US Department of Health and Human Services. "Maybe some of the incentives for people to take things have also increased."

Business vs. Academia

In the business world, proprietary research and trade secrets are jealously guarded. "For corporations, intellectual property represents a vast part of that company's finances," says Peter Mazzaroni, who manages security at Roche Carolina, the Florence, SC, subsidiary of Hoffmann-La Roche. But in the research world, especially among nonprofit universities and institutions, sharing research materials and collaborating on projects have been standard, accepted practices.

After something goes wrong, as when a researcher claims false credit or lab materials are found missing, scientists often are shocked. These things "happen all the time in other areas," says Alvin L. Thompson, chairman of the Educational Institutions Council of the American Society for Industrial Security and head of security at the University of Maryland's College Park campus. "But for some reason, we assume it's not going to happen when it involves academic research."

Partly because of theft issues and partly because of the growing awareness of research value, organizations are adopting stricter policies on sharing. "I have a sense that the sharing of data and materials has become more restrictive," Frankel says. "Before, it was very easy to simply call somebody up and say, 'Would you send me a couple of vials of this or that.' Nowadays, almost every major research university has a materials transfer agreement they expect others to sign."

Courtesy of the Cleveland Clinic Foundation

George R. Stark

In the Cleveland Clinic case, George R. Stark, the institute's director, said that had Okamoto asked, he would have received permission to take samples of the materials with him because "that's standard procedure" and his research had produced no patentable discoveries.²Drez Jennings, a spokeswoman for the Cleveland Clinic Foundation, referred inquiries to law enforcement authorities. Okamoto's attorney, Brent Gurney, declined to comment.

RIKEN has not been charged with any crime. Officials there conducted their own investigation and said they found no evidence of any plan to receive or use materials from the Cleveland Clinic Foundation. In a posting on RIKEN's Web site (www.riken.go.jp/r-world/press/010731e/index2.html), Masao Ito, director of RIKEN's Brain Science Institute, noted, "When a researcher moves, it is common for them to take with them genetic and other materials" provided official permission has been obtained.

In some cases involving laboratory theft, it's simply a matter of money. This seems to have been the case with Taiwanese university professor Chester Ho and Taiwanese businessman Kai-Lo Hsu, who conspired to steal trade secrets for Taxol, the anticancer drug that has made billions of dollars for Bristol-Myers Squibb. Working with a third partner in Taiwan, the group allegedly offered several million dollars to illegally acquire the formula and processes to produce the drug.

The FBI arrested Ho and Hsu in 1997 in an undercover sting operation and charged them under the Economic Espionage Act for conspiring to steal trade secrets. Charges against Ho were dismissed at the government's request. Shortly before trial in 1999, Hsu pleaded guilty to reduced charges and was sentenced to 14 days in jail, two years' probation, and a $10,000 fine.

Stories go Way Back

Allegations of lab theft are nothing new. The beginnings of the biotech industry, in fact, appear to have roots in purloined materials. In 1978 Genentech, then a young start-up company in South San Francisco, Calif., hired Peter H. Seeburg, a postdoc at the University of California, San Francisco. Seeburg had been part of a UCSF team that had made a breakthrough discovery by cloning the cDNA that encodes for human growth hormone (HGH).

Late on New Year's Eve 1978, Seeburg raided his former lab to obtain samples of the cDNA to help him in his new work at Genentech. A few months later, Genentech made a startling announcement: the company had created an expression vector of the cDNA, successfully inserted it into Escherichia coli, and induced the bacterium to produce large quantities of HGH. It was perhaps the first solid demonstration of the commercial viability of biotechnology. The researchers published their achievement later that year in Nature.³

But 20 years later, testifying under oath at a long-delayed patent-infringement trial brought by UCSF against Genentech, Seeburg admitted that not only had he taken genetic samples from the university, he also had used the materials to help produce Genentech's HGH breakthrough, and, he had made a secret pact to cover up the matter. The Nature publication, he said, had not disclosed the university's cDNA as the source. "It was dishonest," Seeburg testified in April 1999. "I regret it, but that's the way we did it 20 years ago. I really am sorry."

For their part, Genentech officials did not contest that Seeburg took materials from UCSF. But they strongly denied that they had used the university's materials to develop their product. The trial ended in a hung jury, with eight of the nine jurors siding with the university on patent infringement. Rather than face a retrial, Genentech gave UCSF $200 million in November 1999 to settle the dispute.

During the 1980s, Genentech successfully commercialized HGH into the multibillion dollar blockbuster drug, Protropin, which propelled the company into one of the world's leading biotech enterprises and helped launch an entire industry. If Seeburg's account is accurate, the biotechnology industry can trace its genesis to purloined lab materials, falsified research records, and a cover-up.

Seeburg currently is director of the Max Planck Institute for Medical Research in Heidelberg. When asked for comment, he replied in a recent E-mail: "I am surprised that this story still captures someone's interest after a quarter of a century has gone by. In all this time, so much nonsense has been written about it that boredom coupled with disgust precludes further comments from me." Sabrina Johnson, a spokeswoman for Genentech, would not elaborate beyond saying, "This is several years old and we said what we had to say back then."

Back to the Present

It is not only commercialization that has value. Increasingly, knowledge itself is seen as having an economic commodity, says Frankel of AAAS. "You don't even have to wait for the technology. In some areas, the basic knowledge is valuable in and of itself." Frankel would like research institutions to make their policies more explicit on intellectual property, especially when collaborators from other organizations are involved.

Strangely, however, theft or the unauthorized removal of materials from laboratories is not considered to be scientific misconduct under rules established by the US government for grant oversight. "We never consider common theft to be misconduct," says Pascal of the ORI. Rather, the federal government's misconduct regulations are limited to fabrication, falsification, and plagiarism. The reason, Frankel explains, is because there are criminal statutes against theft but very few laws against plagiarism.

Ted Agres (tagres@lycos.com)is a freelance writer in Washington, DC.

References
1. AUTM Licensing Survey, FY2000 Survey Summary. Association of University Technology Managers, Northbrook, Ill.

2. E. Marshall, D. Normile, "Intellectual property: Alzheimer's researcher in Japan accused of economic espionage," Science, 292:1274-5, 2001.

3. D.V. Goeddel et al., "Direct expression in Escherichia coli of a DNA sequence coding for human growth hormone," Nature, 281:544-8, 1979.

Securing Your Data
IN FOCUS | Hal Cohen

Thomas Edison, if alive today, might want to rethink his so-called genius ratio of 1% inspiration-99% perspiration to include the energy needed to prevent data and information theft. Computer networks, while extremely powerful, are inherently unsafe. The networks allow the free flow of information and usually operate without a firewall, leaving them thinly protected. Data and information theft are becoming increasingly important issues for researchers, because thieves are becoming more sophisticated, and even the garden-variety hacker has become a true threat.

"You'd be alarmed at the amount of physical theft in labs," said FBI special agent John Chesson at a recent conference. "Scientists generally aren't as focused as they should be on security issues. Even something as simple as physical consideration should be a primary issue." The preferred way to pilfer data is to have direct access to a computer, said Chesson, where disks can be stolen or copied anonymously. The obvious precaution of locking the workstation or the door to the lab could deter a thief, but it is frequently ignored. Chesson made his remarks at a security seminar at Annodyne in suburban Philadelphia.

While it may seem extreme to resort to the authorities, Richard Goldberg, of the US Attorney's Office for the Eastern District of Pa., strongly encouraged the conference goers to do so. "If we think we can pursue it, we will."

Data alteration on a network is widely considered the greatest threat to a lab. Data that have been tampered with, whether onsite or remotely, can be downloaded by thousands of researchers, thereby spreading erroneous information. Independent security consultant Paul Tatarsky says, "The biggest cause of data alteration is a failure to keep up with [software] patches from the vendor. Almost every vendor has a way to automate keeping up with the patches, yet almost no one does it." Patching involves downloading a program to correct errors in already installed software.

In addition to regularly patching, Tatarsky advises backing up the data for safety, using some form of encryption when communicating with others, and installing a firewall. "You'll be safer than most people, and will probably get burned only if someone really hates your guts."

While a virtual guarantee of intellectual property protection is about as likely as a monkey writing the next best seller, several books, programs, and websites are available to bend the odds in your favor.