The year was 1984 and the mouse had cancer.
Philip Leder and Timothy A. Stewart, working out of Leder’s Harvard lab, had finally perfected the process of injecting mice with carcinogenic genetic material.
It’s hard to overstate how important these small, sick vermin were. For years, researchers at competing institutions had tried to find a way to create a reliable supply of cancer-ridden mice for research. With Leder’s and Stewart’s discovery, the study of cancer became far easier.
The medical implications of the discovery are only one part of the story, though. That same year, Harvard submitted a patent application to the U.S. Patent and Trademark Office for a “non-human” animal containing a carcinogenic gene sequence. When the application was finally accepted in 1988, Harvard exclusively owned the idea of giving a mouse cancer.
That patent kicked off a decades-long series of Harvard patent filings for the mouse, all of which raised pressing questions about the ethics of profiting from an essential cancer research tool. Leder’s and Stewart’s “Oncomouse” changed not only the face of cancer research, but also the way universities manage their intellectual property.
Intellectual property has a long and complicated history. In the United States today, it comprises three main entities: patents, trademarks, and copyright. Trademark deals with the names or brands of things (Coca-Cola, Harvard’s crest, “CS50”). Copyright deals with works of authorship (books, plays, poems).
Patents cover inventions—products or processes that solve a particular technological problem. If you hold a patent on something, you control, for the 20-year lifespan of the patent, who uses that invention. Patent holders can choose to license their inventions for a fee to others interested in using them or withhold their use altogether. Licenses can be exclusive (meaning no more than one licensee can use the invention) or non-exclusive.
At universities, the process by which inventions made in the lab are patented and subsequently commercialized is known as tech transfer. At Harvard, like virtually every other research university in America, tech transfer is managed by the school itself. While researchers are listed as inventors and are entitled to a cut of any royalties, the university ultimately owns and manages all patents. Specifically, these decisions fall to the “tech transfer office,” which at Harvard is called the Office of Technology Development.
{shortcode-906878dc79604d118aca8139f5b0e889bef08c6d}
If Harvard’s purpose is, to borrow the language of its current president, “the creation and dissemination of knowledge,” the Office of Technology Development (OTD) has significant control over the dissemination portion of that mission as well as the increasing levels of corporate-funded research at Harvard.
Ever since 1980, when universities were first allowed to own the inventions developed in federally-funded research labs, the tech transfer process has necessitated trade-offs between their profit and the public good. Since the Oncomouse, universities like Harvard have attempted to reorient tech transfer efforts to empower faculty inventors and benefit society. However, to some non-faculty inventors, like the undergraduates, graduate students, and postdocs who often work with tenured professors, the process does not always seem fair. Some say that Harvard’s tech transfer process allows faculty to take the lion’s share of both the profit and prestige of successful inventions, leaving other inventors unsupported.
As Harvard, like many research universities, focuses increasing attention on the engineering disciplines, these ethical issues will become more urgent than ever.
***
Harvard’s management of the Oncomouse patents attracted significant criticism. After securing the patent for the mouse, the University licensed its invention exclusively to Dupont, a Virginia-based industrials conglomerate and a big financial backer of Leder’s lab. Any lab hoping to use “oncomice” for research had to buy them through Dupont.
According to intellectual property scholar Jacob H. Rooksby’s recently-released book “The Branding of the American Mind,” Dupont sold the mouse at about five times the cost of other experimental mice and also required buyers to agree to “reach-through rights.” The agreement required customers to give Dupont a cut of the revenues from any invention made using the Oncomouse.
Rooksby describes Harvard’s Oncomouse dealings as a clear sacrifice of the public good in favor of higher licensing revenues. That the taxpayer-funded National Institute of Health in large part bankrolled the invention of the mouse makes Harvard’s actions seem even worse to Rooksby.
“This was public funding that led to this discovery,” Rooksby says in an interview. “So I think it is incumbent on these institutions… to use these patents in the public interest.”
Sitting in his Smith Center office 32 years after Harvard filed its first Oncomouse patent application, current head of Harvard’s OTD Isaac Kohlberg says a lot has changed.
“I can only say that we have learned a lot since then,” Kohlberg says. “I know we don’t structure agreements like this anymore.”
Now, according to Harvard Medical School professor Bruce Bean, “research tools” like the Oncomouse are seldom even patented, let alone licensed exclusively to one company.
These days, Kohlberg says, OTD’s “mission [is] all about societal impact,” and serving the public interest.
“You have to hold this mission,” Kohlberg says, shaking his fists animatedly in the air. “The societal impact comes first. And when you hold this view, you hold it like a mountain.”{shortcode-c17fec235465202aff842dedf6d8456e1e951cfc}At OTD, Kohlberg oversees a 50-person staff littered with Ph.Ds and J.Ds. This highly credentialed group has the final say over what Harvard patents and how it uses those patents. The challenge for his team, one that Kohlberg thinks his staff has “really mastered,” is “striking the balance” among “an intersection of competing interests between universities and schools and the external world and the faculty.”
As they exist today, tech transfer offices like OTD trace their origins to 1980. That year, four years before the creation of the Oncomouse, President Jimmy Carter signed the Bayh-Dole act. For the first time, universities could retain ownership of (and patent rights to) any inventions resulting from federally-funded research. Previously, the government owned that intellectual property.
By placing the onus for commercializing inventions on individual universities, Congress made a bet that universities could translate inventions from the lab to the market better than the government could.
David Winwood, president of the Association of University Technology Managers, the industry lobbying group for tech transfer, says that before Bayh-Dole, when the government owned the intellectual property resulting from federally funded research, “things [would] just go away and die” post-invention.
“It’s proven a successful mechanism to take basic discoveries [and] pass them through this translational process into the private sector,” Winwood says.
Bayh-Dole also created a new potential revenue stream for universities. Now, schools can license discoveries exclusively to one company (as Harvard did with Dupont for the Oncomouse) or non-exclusively to many. They can also create their own start-ups and license patents directly to them.
The second part of OTD’s mission, Kohlberg says, is “the generation of revenues that then flow back into research.”
In fiscal year 2016, Harvard brought in $37.8 million in licensing revenues from its patent holdings. Though certainly not nothing, this sum pales in comparison to Harvard’s total research expenditures, which in 2014 exceeded $800 million.
{shortcode-c957aac5c5ecb3af83ac1cef6c79516018fe91f2}
“[Tech transfer] is not profitable for the university as a business,” says former MIT tech transfer head Lita Nelsen. “If you look at it statistically across the country, the total returns... [are] about 4 percent of the research budget that spawns it,” Nelsen says. “Statistically, it’s not very much.”
What’s more, Nelsen says, the bulk of licensing revenues can come from just a handful of successful patents. It’s often difficult to predict which patents will do well on the market before deciding whether to file an expensive patent application (applying for a patent costs around $30,000). Nelsen believes universities go through all this trouble for relatively little profit because of their desire to benefit the public good.
“You’re not going to get rich from tech transfer unless you get lucky,” Nelsen says. “But if that’s how you plan on getting rich, buy lottery tickets.”
***
Harvard and Kohlberg, as it turns out, did get pretty lucky this year. More than half of this fiscal year’s licensing revenues came from pharmaceutical company Merck’s $20 million upfront licensing for a molecule developed by chemistry professor Matthew Shair. That molecule may lead to new drug options for a certain type of leukemia. In addition to the upfront payment, Harvard can expect royalties if Merck develops a usable drug.
Though patenting and licensing constitute a lot of OTD’s duties, the office also focuses heavily, as its name might suggest, on the development of technologies.
“When I came here we changed the name from ‘Technology Transfer’ to ‘Technology Development’ because it’s not just the transfer that we do,” Kohlberg says. “We develop [inventions] together with our innovators.”
In 2007, two years after Kohlberg’s arrival, OTD launched what it called a “biomedical accelerator” to fund Harvard research projects that seem promising, but are not yet developed enough to attract outside investors. Any Harvard professor working on such a project can apply to the accelerator for a grant. The accelerator, since funded by a $50 million gift from the Blavatnik Family Foundation, supported Shair’s early work on the molecule.
“I couldn’t have done it without the Blavatnik Accelerator,” Shair says, sitting in his third-floor office in Mallinckrodt labs. These labs have churned out some of Harvard’s most successful patents and start-ups.
Shair turned to OTD after initially reaching out to federal funding sources.
“When he first had these ideas to commence his research, the NIH turned him down. Can you imagine? The NIH!” Kohlberg says. Only about 18.1 percent of applications for National Institute of Health grants eventually receive funding. “He goes to the NIH with a grant application to sponsor work, to develop a drug... for a cancer that there is no treatment for. NIH turned him down… Then he came to the Blavatnik accelerator, we started to fund it, and then we funded it up to a point that it really became of great interest.”
OTD worked closely with Shair throughout the process of deciding which pharmaceutical company to work with.
“Every time I went to a company a person from OTD would come with me,” he says.
Shair considers the accelerator, as well as the constant contact he had with OTD, hallmarks of Kohlberg’s decade-long tenure.
“Isaac has really focused on doing what’s best for investigators, for the faculty, for the programs, for the valuation of those programs,” Shair says.
Alán Aspuru-Guzik, another chemistry professor, also holds Kohlberg and the OTD in high esteem.
“Since Isaac Kohlberg is here, OTD is like Real Madrid and Barcelona,” Aspuru-Guzik says, referring to two of the world’s most dominant soccer teams. “They are really first class.”
Aspuru-Guzik most recently worked with OTD to commercialize his research on OLED technology, a special kind of LED light that works better in darker environments. The work was sponsored by Samsung, which is interested in the potential uses of OLED technology in their products, according to Aspuru-Guzik.
In addition to directly funding some projects through accelerators, OTD also coordinates research with corporate sponsors. From fiscal year 2006, the year Kohlberg arrived at Harvard, to fiscal year 2016, the amount of corporate-sponsored research funding at the University has more than quintupled, from $9.1 million to $48.4 million. Like the accelerators, this focus on corporate funding has been driven in part by flagging federal support for research.
{shortcode-9cd56272a928a0526492d8b5576d8778510d3b90}
In addition to attracting funding from the corporate world, OTD facilitates the movement of graduate students from the academy to the marketplace. Start-ups based on inventions created in the lab provide jobs for graduate students and post-docs in an often-anemic academic job market. In such cases, OTD oversees the transfer of human talent as well as intellectual property.
“If you ever become my grad student, you will become a bottle eventually,” Aspuru-Guzik says, gesturing toward a shelf of empty champagne bottles in the corner of his office. In chemistry, it is traditional to mark a graduate student’s graduation with a bottle of champagne. Many of Apsuru-Guzik’s bottles are now working for start-ups, as opposed to research universities.
***
While Kohlberg’s OTD seems to have impressed certain faculty, a recently-settled high-profile lawsuit alleged that perhaps OTD’s coziness with professors comes at the expense of protecting the intellectual property claims of non-tenured researchers like graduate students and post-docs.
The lawsuit in question was brought by former Harvard graduate student Mark G. Charest against both the University and chemistry professor Andrew G. Myers, Charest’s graduate advisor.
Charest and other graduate students worked in Myers’s lab to develop a synthetic version of a type of antibiotic. Myers told Charest that if they succeeded, they would make “a [explicative] (sic) billion dollars,” according to court records.
The group was ultimately successful and Charest was listed as the first author when the group published their findings in the prestigious journal “Science.” (First authorship is traditionally granted to the researcher who made the greatest scientific contribution to the work.)
So, when OTD licensed the discovery to Myers’s start-up, Tetraphase, Charest assumed he would get an equal share of the 35 percent of royalty revenues that OTD gives to inventors (the rest goes to Harvard departments). When it came time to divvy up the royalties, however, OTD gave Myers a full 50 percent of the inventors’ royalties, and the other four inventors had to share the other half. Charest’s complaint also alleges that Myers conspired with OTD to “enrich [himself] at the expense of the non-faculty inventors.”
Myers did not respond to multiple requests for comment for this article and Kohlberg said he had nothing to add to earlier University comments on the case, which denied wrongdoing on Harvard’s part.
When Charest expressed his concerns to Myers, the professor allegedly told him to “tread lightly,” “be careful,” and to “ think about [his] career.” Later, according to the complaint, Myers refused to act as a reference for Charest when the latter was applying for a job at a venture capital firm, despite having given him a glowing recommendation before the dispute.
Like most intellectual property lawsuits, the Charest case was complicated and contentious. In addition to addressing the antibiotic patent dispute, it also raised concerns that Harvard’s intellectual property appeals process was insufficient. In a January 2014 hearing, federal judge Douglas P. Woodlock described Harvard’s process as “pretty shoddy stuff.”
When Charest brought his complaints to OTD, the University had no standing committee on intellectual property, despite the provision for such a committee in Harvard’s public intellectual property policy. Instead, then-Provost Steven E. Hyman appointed an ad hoc committee to handle Charest’s complaint. Charest alleged that the committee had a conflict of interest given that it was “comprised of science professors with ongoing commercialization projects with OTD.”
“The fishbone in my throat is the degree to which the [intellectual property] appeal that was offered [by Harvard] is... like a teasing illusion, like a munificent bequest in a pauper’s will,” Woodlock said at the hearing. He described Harvard’s lack of a standing committee to handle disputes as evidence of its “raggedy-ass approach” to intellectual property complaints.
Ultimately, the court dismissed five of Charest’s seven claims, including all charges against Myers. Before the other two claims, including one about the alleged lack of fairness in OTD’s appeals process, could proceed to trial, Charest and Harvard settled.
“One of the reasons [the appeals process] may be ‘raggedy-ass’ is because [Harvard] had never actually had to go through it before,” said Michael J. Tuteur, the attorney representing Harvard, at the Jan. 2014 hearing. “And maybe this is a lesson learned.”
In one respect at least, OTD has not yet learned its lesson. Harvard still has no standing committee on intellectual property to resolve potential disputes, despite a detailed description of the duties of the non-existent committee in Harvard’s intellectual property policy.
Asked about the committee, Kohlberg says “it is something we are considering,” before adding that “there will be” a committee at some point. Kohlberg insists he is not concerned that Harvard’s tech transfer system disadvantages graduate students.
Charest’s attorney, Brian O’Reilly, believes Charest’s case will inspire other graduate students to speak out about unfairness in the intellectual property process.
“I’ve had a number of students and postdocs approach me with issues they’ve had,” O’Reilly told The Crimson this summer. “I think we’ll see an increasing willingness on the part of students to challenge these power imbalances in their universities.”
Nelsen says that when she led MIT’s tech transfer office, she did not encounter many cases like Charest’s, but admitted that such disputes are “unpleasant” when they do arise.
“Whenever you’ve got money on the table you’re going to have fights, but it was rare,” says Nelsen. “It’s not the kind of thing that you want to spend time in the newspapers.”
***
Graduate students are not the only non-faculty researchers at Harvard working on potentially patentable work. As student interest in engineering disciplines has skyrocketed over the past few years, more and more undergraduates are inventing materials that OTD could patent.
{shortcode-7905a591008c558a53dbc9a13743603d097a3fcd}
Every undergraduate student pursuing an Engineering Sciences degree, for instance, must take ES96, a class structured as one long engineering project in which students work to solve a real-world problem. In past years, students in the class helped Harvard’s Facilities and Maintenance office remove snow from campus, and developed potential ways Harvard’s facilities could respond to climate change.
In the spring of 2015, kitchenware retailer Williams-Sonoma wanted a better barbecue. The company tasked the class, taught by bioengineering professor K. Kit Parker, with devising a better way to smoke brisket, a notoriously difficult meat to cook. The class aimed to create a high-tech variant on the popular “Big Green Egg” barbecue smoker.
For a semester, students spent hours every week smoking hunks of barbecue brisket, often working until the wee hours of the morning.
“I smoked so much and was there for so many of the smokes that I actually destroyed the goblet cells in my eyes. By the end of the class I’d had 12 conjunctivitis attacks, pinkeye essentially,” says Michel Maalouly ’16. “I’d end up having literally pus all over my eyes, 12 times. So by the last smoke that lasted 96 hours for the final presentation I was wearing goggles. I was wearing a mask.”
Through pus and pain, though, Maalouly and his classmates kept working on the smoker.
“I’d get an attack, I’d go to UHS, two hours later I’d be back on the barbecue,” says Maalouly.
Parker drove the grueling pace and high standards, according to students in the class. Early in the course, Jerry Chang ’16, another member of the class, learned, in no uncertain terms, that his PowerPoint slide-making skills were not up to Parker’s standards.
“Scrub this crap again. I want the fonts done properly and images I can read,” wrote Parker in an email Chang shared with The Crimson. “You better step up your game if you want to be an engineer because your attention to detail is bested by a Starbucks Barista right now, much less an engineer that builds things that matter.”
“If you don’t do well with harsh, intense criticism, don’t work with Parker,” advised one student in a Q-Guide course evaluation.
Parker wrote in an email that it would be “highly inappropriate” to comment on individual students in the class, adding that he was “very proud of the students in that class.”
“[The course] marks a phase transition from being a student to being an engineer… and that is not a routine transition. Its very hard,” Parker wrote. “My goal is to produce the best engineers in the world, worthy of society’s trust and prepared to meet their needs with technological options for policy makers to choose from.”
The smoker the class produced was quite successful, winning the praise of barbecue experts and a slew of positive media coverage from outlets like the New York Times, the Boston Globe, NPR and Wired. But behind the acclaimed barbecue smoker was an intellectual property process that left some with a bad taste in their mouth.
As it became clear that patenting the invention might make sense, Parker and course teaching fellow A. Peyton Nesmith asked students to notify course staff which parts of the project they felt they had contributed to and to turn over their design notebooks, which students maintained throughout the semester to record what intellectual property they had worked on. Ultimately, 10 students were awarded inventorship on a patent application for the smoker.
In addition, Harvard filed a second application that listed only Parker, Nesmith, and three students as inventors. Parker and at least two students from the class then created a company, “96 Solutions,” (since renamed “Desora”) to develop and ultimately sell the smoker.
In the eyes of some students, this second patent was an attempt by Parker to control the terms of any potential commercialization of the smoker. Both Chang and Austen Novis, another student from the course, saw this second patent that way
But OTD staffer Mick Sawka said that students had no cause for concern, writing in an email that Harvard would allow students access to any intellectual property “needed to practice the invention developed during the class.” Citing ongoing negotiations between OTD and Desora, Parker deferred all comment on the intellectual property to OTD.
Still, Novis felt that the intellectual property discussions were “not transparent at all.”
Maalouly, on the other hand, found the handling of the patent process fair and transparent. He later joined Parker’s company and is currently working on developing the smoker. Maalouly argued that even if he wanted to, Parker would not be able to claim the intellectual property all for himself.
“[Parker] does not have the power to decide what happens to the IP,” says Maalouly, citing OTD’s ownership of Harvard-supported patents.
The office’s self-professed commitment to faculty collaboration, however, suggests professors would have significant input in intellectual property decisions.
***
Winwood, the lobbying group head, says that many people who criticize the tech transfer process do not really understand it.
“One of my predecessors… said ‘the problem is, our story has to be told in tomes, and we live in a bumper sticker community,’” Winwood says. “Everybody wants the soundbite, and it’s really complicated stuff.”
Complicated or not, it looks like tech transfer issues will only become more urgent, both at Harvard and nationally.
In the past 10 years, Harvard has filed more patents, launched more start-ups, and granted more licenses than ever before, according to data compiled by AUTM, the tech transfer lobbying group. At Harvard specifically, an institutional pivot to the engineering disciplines, including a new multi-million dollar engineering campus in Allston, all but assures a larger role for tech transfer in the near future.
And while Kohlberg and the tech transfer industry may have “learned a lot” since the days of the first Oncomouse filings, the laws surrounding intellectual property in higher education have changed relatively little since Bayh-Dole.
Shades of the Oncomouse controversy have continued to dog OTD. As recently as 2012, Harvard filed a federal court appeal to extend the life of some Oncomouse-related patents that the U.S. patent office had deemed expired. According to OTD spokesperson Caroline Perry, Harvard was legally “obliged” to file these appeals because of the terms of its original agreement with Dupont in the 80’s.
Tech transfer offices are still legally able to do all the things that made the Oncomouse agreement such a target of criticism. OTD still has extraordinary amounts of largely unchecked control over what happens to the knowledge and inventions produced in Harvard’s halls. Whether OTD wields that power responsibly depends almost solely on whether Kohlberg’s office truly holds on, “like a mountain,” to its stated mission of prioritizing the public good.
Rooksby, the intellectual property scholar, worries that despite its stated mission, OTD and offices like it might be more interested in making money than they like to let on.
“Often there’s a focus on revenue above all else, because that’s how you make your boss happy. Several [tech transfer managers] have said to me off the record ‘that’s how you get recognized in this business.’” Rooksby says. “You get noticed by generating revenue against all odds.”
Rooksby added, though, that for “more financially stable” institutions like Harvard ($2 billion hit to its endowment notwithstanding), there is less pressure to produce revenue at all costs.
One way to ensure that offices truly act in the public good, says Rooksby, is to promote broader public understanding of the tech transfer process.
“Intellectual property as a topic is misunderstood… but the issues are important,” says Rooksby. “They are important in isolation and in aggregate. These problems are too important and too impactful on the public to just let the lawyers figure them out.”
