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Few neighborhoods in Cambridge have seen their fortunes change as dramatically as Kendall Square.

Kendall was once known for churning out soap and vulcanized rubber, then manufacturing electronics as the Cold War raged. It was, at points, left desolate by deindustrialization and the loss of a planned NASA campus. But today, Kendall has been reborn — as the glittering, glassy heart of America’s biotech industry.

For many companies, Kendall Square’s status as a global center of biotechnology firms and research makes them willing to pay top dollar to be in its vicinity. And proximity to MIT — which birthed many of the industry’s foundational technologies and established Cambridge as the place to be — only enhances the draw.

Kendall is a place where Cambridge used to spend money developing its infrastructure to attract firms, noted Tom Evans, the director of the Cambridge Redevelopment Authority. Now, Kendall is so attractive that the city can require firms to develop nearby infrastructure in order to build on the land.

“We’ve actually been able to flip the formula,” Evans said.

As a new field of biotech research, born in the 1970s, morphed into a lucrative industry, the old brick halls of Harvard have come to feel distant from Kendall Square’s glass towers. Many biotech executives are careful to give their thanks to MIT, Kendall’s nearest neighbor, when touting the successes of Kendall Square research and companies.

In 10 interviews with The Crimson, Nobel laureates, CEOs, and pioneering scientists from that era said that work at both Harvard and MIT brought about the dawn of biotech. But Harvard — wary of the commercial turn in cutting-edge life sciences, wedded to its theoretical research commitments, and without any land to spare — turned away in the early 1980s.

Now, as Harvard has poured millions into its Enterprise Research Campus and Science and Engineering Complex in Allston, the University is gradually reversing that course, venturing down a path it once relinquished decades ago.

Biotech’s Beginnings

The story of modern biotechnology traces back to a single innovation: recombinant DNA.

DNA recombination involves combining genes from different organisms into one DNA molecule, allowing human genes to be inserted into organisms like bacteria. This, in turn, has enabled the mass production of proteins like insulin for treating diabetes or alpha interferon for cancer treatment.

The recombination breakthrough, made by pioneering scientist Paul Berg at Stanford University in 1971, soon spread to the other two leading institutions of biology research in the U.S., Harvard and MIT.

Harvard at the time had one of the strongest biology departments in the nation — between the 1950s and 1980s, it was home to ten current or eventual Nobel Laureates in chemistry and medicine, all of whom worked or trained at Harvard’s Biological Laboratories.

Walter Gilbert ’53 at Harvard and Philip A. Sharp at MIT, who each won Nobel Prizes in the 1980s, were leading the charge in recombinant DNA research on the East Coast.

As scientists began to raise concerns about the dangers of creating unknown DNA molecules, through forums like the famous Asilomar Conference on Recombinant DNA, Gilbert developed a method for sequencing DNA, for which he shared half of the 1980 Nobel Prize in Chemistry. Sequencing created clarity about which genes were being moved around.

“And so there begins to be, during the late 70s, an effort to move genes around deliberately,” Gilbert said.

“It was a revolutionary time, largely because of recombinant DNA, and Wally played a very key role in connecting recombinant DNA with actually sequencing,” said George M. Church, a Harvard professor of genetics who worked with Gilbert’s lab as a graduate student at the time.

Despite Kendall Square’s association with MIT — owing to a history of joint development —Harvard’s biology department played a pivotal role in advancing the industry’s most foundational research in the beginning.

Eventually, events at Harvard would push Cambridge to emerge as the first city in the world to regulate recombinant DNA research — and thus, the frontier of the emerging biotech industry, as the one place in the United States that had the necessary stability for companies and banks to invest in the risky new venture.

A Safe Home for Investment

When Harvard eventually sought to build new labs for its recombinant DNA research, Cambridge Mayor Alfred E. Vellucci — at the time already hostile to Harvard as an institution — jumped at the chance to antagonize the University, raising serious safety concerns about the research.

“Al Vellucci, who was mayor at the time, was hoping to make himself a national reputation based on the recombinant DNA,” Gilbert said.

Receptive to the mayor’s concerns, the city council soon imposed a six-month moratorium on recombinant DNA research and assembled a commission with professors from Harvard and MIT to study the safety of inserting foreign genes — including potentially dangerous viruses — into living organisms.

Wild, highly publicized stories about recombinant DNA incited panic in the public, who worried that well-meaning experiments might go horribly wrong.

“In Dover, MA, a ‘strange, orange-eyed creature’ was sighted and in Hollis, New Hampshire, a man and his two sons were confronted by a ‘hairy, nine foot creature.’” Vellucci wrote in his letter to the National Academies of Science, referring to sensational reports in the Boston Herald American.

The commission’s efforts culminated in the passage of the Cambridge Recombinant DNA Technology Ordinance by the city council 1977. The ordinance was critical in creating a stable, predictable business environment that would be the backbone of the industry soon to come.

The ordeal was catalyzed by Harvard’s need to build a new lab to house the research — which required city approval and permitting — in order to receive its NIH grant of about $500,000. The NIH, citing safety concerns, had demanded the new lab as a condition for its grant.

The ordinance was the structure provided by Cambridge’s regulations for university research that made the city ideal for the new endeavors of Biogen, the first biotechnology company to move to Kendall Square.

The company was founded in 1978 by Gilbert, Sharp, and British biologist Kenneth Murray, and became the first to obtain a commercial license for DNA recombination.

“Why do we set up the laboratory in Cambridge? Well, we do it because Cambridge already has a discipline about how to handle recombinant DNA,” said Gilbert.

“Biogen was assured that this issue wouldn’t flare up politically and close them down,” Sharp said.

The founding of Biogen represented a first instance of the relationship between academia, which provided the scientific foundations for novel biotech, and a burgeoning biotech sector, which translated these discoveries into commercial technology.

“All this technology was only found in universities,” Sharp said. “There was almost none in the private sector.”

Sharp emphasized that proximity to Harvard and MIT was “a tremendous advantage” allowing Biogen to “keep their professional relationships” to the scientists developing the technology, who “could also be involved in direct translation.”

Two Paths Diverge

By the 1980s, many faculty at both Harvard and MIT were now reckoning with the idea that their research could be turned into marketable products, sparking new debates around the ethics of commercializing federally funded research.

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Though it would be years before Biogen successfully developed their first drug — Avonex, used to treat multiple sclerosis — the excitement following their incorporation spurred the growth of other biotech start-ups at the time.

“For a long time, there was a group called the ‘Bygones’, which were people who’d been at Biogen and then went on to other companies,” Gilbert said.

Mark S. Ptashne and Tom Maniatis, two biology professors at Harvard who were looking to establish a new genetic engineering firm called the Genetics Institute, had an idea: give the university an active role in a company that emerged from its research.

Ptashne reached out to Harvard for help, proposing that in return for support with recruiting scientists and attracting venture capitalists, the University would be given a minority stake in the company, earning royalties on its profits.

But the idea that the University would make money off a private venture was controversial. When other faculty caught wind of the plans in 1980, then-President Derek C. Bok came under fire, and the issue quickly made national headlines.

Faculty voted to forbid Harvard from moving forward with the proposal. They feared such ventures would create unhealthy competition for trade secrets among professors and conflicts of interest for the university.

“Harvard should not take such a step unless we are assured that we can proceed without the risk of compromising the quality of our education and research,” Bok said at the time.

Bok’s withdrawal of the proposal — which The Crimson at the time declared “The Ptashne Fiasco” — was a turning point in the university’s still-uncertain relationship with the biotech industry that it had helped create.

While Harvard continued to sponsor biotech research, and many individual faculty maintained private sector affiliations, the institution as a whole remained relatively detached from fast-growing local industry.

That moment was a watershed. Even as Harvard drew back, MIT — which until that point was largely co-equal with Harvard in the new sector — leaned in.

Oriented around applied sciences that translated easily into commercial applications, MIT was far better positioned to take advantage of the emerging new sector. The school took the opposite tack from Harvard, founding a center for entrepreneurship in 1990 that was meant to commercialize technology created by its students.

MIT also had the benefit of well-positioned land holdings. The university had been proximate to industry that it was meant to foster since its founding in 1818, when it was strategically placed next to the earliest factories in East Cambridge.

When Kendall Square and East Cambridge deindustrialized as part of a national trend 150 years later, the area became run-down and populated by vacant industrial sites. But the empty and cheap land surrounding MIT was just the thing new biotech companies were hoping to base themselves on.

“The fact that there was developmental open space available to develop immediately across the street from MIT meant that this was a very attractive place,” said Sharp.

Brian Kavoogian, CEO of National Development, pointed to Harvard’s lack of proximate land as another key obstacle further preventing them from matching MIT’s industrial success.

“There’s many entrepreneurial Harvard faculty members. So I think, once again, it’s a lack of just simply a lack of buildable land,” Kavoogian said.

MIT’s land investment company began leasing land in its north campus — originally meant for academic expansion — to commercial tenants, primarily biotech companies. Today, it reaps hundreds of millions from its prime real estate in Kendall Square.

By the 1990s, MIT had taken the spotlight in the story of Kendall — and of the biotech industry. Even as essential theoretical and medical research at Harvard continued, the University itself faded into the background.

Harvard’s Return

But, ever so slowly, Harvard is trying to change course. At the turn of the 21st century, new leadership at Harvard argued the university should shift its willingness to embrace the private sector, and began to oversee expensive new projects that may catch Harvard up to MIT.

In 2001, President Lawrence H. Summers declared in a speech to several hundred physicians, nurses, and administrators at Beth Israel Deaconess Medical Center that the University hoped to make a new foray into applied science.

“We need, as science evolves, to continue to think about how we make sure that our research finds maximum application with maximum rapidity,” Summers said.

The then-president’s speech emphasized the need “to work with the private sector,” “support entrepreneurship,” and “make sure research moves from the bench to the bedside.”

Then, over the first decade of the 2000s, Harvard founded a string of new institutes aimed at translating biomedical research into commercially viable technologies.

“To do actual real drug discovery in university would be very difficult, complicated, because you have to bring all those different disciplines together, which is often counter to how universities are structured,” said John Tallarico, Global Head of Discovery Sciences at Novartis Biomedical Research.

In 2003, Harvard and MIT together founded the Broad Institute, with the goal of transforming medicine through genomic research.

“A place like the Broad Institute or the Whitehead, they bring together many different disciplines of science together into a single organization with the aspiration to help create the beginnings of drug discovery,” Tallarico added.

In 2009, the university founded the Wyss Institute for Biologically Inspired Engineering near Boston’s Longwood Medical Area, marking another venture into research with direct practical applications.

“The vision was to have the intersection of biology and engineering. Harvard at the time was pretty poor at engineering,” Church, one of the center’s founding members, said.

The year before, Harvard proposed creating a School of Engineering and Applied Sciences. It would become the first new school Harvard had added since the School of Government in 1936, which later became the Harvard Kennedy School.

SEAS’ location in Allston represented a realization of Summers’ original vision from the early 2000s — and anchors what many see as an effort by Harvard to create its own kind of Kendall Square, or at least an extension of it a few miles away.

Harvard has spent 30 years gathering hundreds of acres of land in Allston, although its prolonged transition into biotech there will not be fully complete for at least another 20 years, with the completion of Beacon Park Yards.

“It is already time for Allston, given the lack of capacity in Kendall Square,” said Kavoogian.

Now, Harvard is in the process of constructing its Enterprise Research Campus, which is meant to be a new “innovation district” — while serving other mixed uses — where Harvard will lease lab space to companies from startups to giants.

The venture will almost certainly be profitable, though many wonder if Harvard can ultimately catch up to what it missed in the 1980s.

“People joke about having to get a passport to cross the river,” Maggie O’Toole, CEO of LabCentral, said. “People want to be near where their founders are. So obviously, you know, that’s on the Cambridge side of the river, where MIT and Harvard are.”

—Staff writer Stephanie Dragoi can be reached at stephanie.dragoi@thecrimson.com.

—Staff writer Thamini Vijeyasingam can be reached at thamini.vijeyasingam@thecrimson.com. Follow her on X @vijeyasingam.