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Boston's Biotech Moment

The future is moving out of dusty library stacks and into pristine laboratories on both sides of the Charles River, making this area the national leader in biotechnology. The boom is driven by a new breed of intellectual wearing a white lab coat and using science to breach the barrier between academia and commerce.

The future has big red eyes.

This is the whole future here, too. This is the future of Boston's economy and Boston's development, and of Boston's traditionally limitless perception of itself as the, you know, Athens of America. The future has moved out of the dusty library stacks and into pristine laboratories in dozens of places on both sides of the river. The image of Boston's public intellectual no longer is a tweedy gent with leather patches on his elbows, discoursing on economic history, the way it was in the 1920s and '30s. It's not the rag-wool-sweatered computer phenoms out along Route 128, as it was in the high-tech 1970s and '80s, and it's not a shark in a suit, like the financial-services whiz kids of the 1990s. It's someone in a white coat, working in the spotless heart of a new building, looking at the future one fly at a time.

"Isn't it beautiful?" says Dr. Mel Feany.

Feany is a researcher at the Harvard Medical School's Center for Neurodegeneration and Repair, and her specialty is working with drosophila, the common fruit fly. Feany is working with drosophila in order to help discover the causes and cures for catastrophic neurological diseases like Parkinson's and Alzheimer's. She and her flies are the most basic parts of a biotechnology industry that is changing not only medical science, and not only our most basic understanding of ourselves, but which already is well on the way to transforming Boston's image of itself in profound and myriad ways.

Walk out of Feany's laboratory, and you can see an industry transforming an area as surely as steel did Pittsburgh or automobiles did Detroit. Its questions are huge and fundamental: Who are we as a species, and what do we want to be, and who are we as a city, and what do we want to be? In all its manifestations, the biotechnology moment in Boston is a question of intellectual and cultural identity. All of the others are still around -- the humanities pipe-smokers and the computer drones and the banking carnivores -- but the Boston intellectuals today are looking through microscopes, and they are possessed of an astonishing catholicity of interests. Because biotechnology requires a familiarity with a variety of scientific disciplines -- physics, biology, mathematics, computer science -- it attracts people whose passions seem boundless and seem to run in several directions at once. In a sense, these people are throwbacks to the old days when a brilliant physician could quote Homer in the original Greek.

"It's much more likely that your top scientist can whistle the melodies from three sonatas than it is that your humanities-trained person can pass the science section of the MCAS," says Josh Boger, a PhD who is also the chairman and chief executive officer of Vertex Pharmaceuticals.

The new Boston intellectual wears a lab coat and glasses and works in a clean place alive with low hums of various pitches and tones. That's the new topography of the Athens of America. Its future has big red eyes. It flies on a thousand tiny wings.

o, roughly 5,000 years ago, the Sumerians got thirsty. They found a way to make beer using yeast, a living thing, if a particularly noxious one. And biotechnology was born.

"The rest of this is all pretty heavy for what's really beer-making on a grand scale," says Marc Goldberg, the chief executive officer of BioVentures Investors, a Boston venture-capital firm that specializes in the biotechnology industry.

The numbers tell the story starkly, and they measure precisely the new lay of the land. The numbers are so vast, and they arrived with such apparent suddenness, that the term "biotechnology industry" itself seems to render any new definition meaningless almost instantly. "Every four or five years," says Goldberg, "you have one of these public awareness moments. This time, though, there's such a general awareness that we here are a worldwide leader that there is some real substance behind it."

The moment is made up of more than numbers, though. It's also made up of glass and steel. Just this past year, Boston and its surrounding area have seen the following:

* The opening of the 525,000-square-foot, $260 million New Research Building at the Harvard Medical School, which is aimed at aligning scientists from many disciplines in a single facility. More than 800 researchers and staff now work there.

* Also at the Harvard Medical School, a new "systems biology" department, the first new department of any kind established at Harvard in more than 20 years. "Systems biology is like the old definition of pornography: I don't know what it is, but I know it when I see it," explains Dr. Marc Kirschner, head of the new department. "It's a marriage of the natural science and computer science with biology, to try and understand complex systems."

* An ambitious program called the Broad Institute -- funded in part by a $100 million grant from philanthropists Eli and Edythe Broad -- which brings together Harvard, the Massachusetts Institute of Technology, and the Whitehead Institute for Biomedical Research in a concentrated effort to use genomics to find cures for various diseases.

* A grant of $120 million from the National Institutes of Health to Boston University to finance the construction in the South End of a new high-level biosafety facility as part of a national program to combat both mass infectious disease and the possibility that such disease may be used as an agent of bioterrorism.

* In May, Swiss pharmaceutical giant Novartis announced that it was establishing the Novartis Institutes for BioMedical Research Inc. in Cambridge, which moved the company's entire research division there from Basel, Switzerland, at a cost of $255 million. The move meant 400 new jobs immediately, and the institute has said that it plans to employ as many as 1,000 researchers and scientists over the next five years.

* Two researchers working in the life sciences -- James Collins, a biomedical engineer at Boston University, and Harvard biophysicist Xiaowei Zhuang -- were among the 24 recipients of this year's MacArthur Foundation "genius" grants, worth $250,000 each.

* This past summer, Boston mayor Thomas M. Menino committed the city to hiring a biotechnology "czar" to oversee the consequences of the industry's growth.

As the biotech industry has matured through its first iteration, many of the initial fears about it were allayed, and a lowering occurred of the traditional barriers between scientific academia and scientific commerce. Biotechnology formed itself around new scientific and economic modalities until, now, Boston finds itself at the center of what has become a $310 billion industry that includes everyone from researchers in laboratories to venture capitalists on the make.

USA Today reported in November that revenue-starved state governments have latched onto biotechnology as firmly as some of them have attached themselves to casino gambling. According to a recent study by the Brookings Institution, biotechnology is the primary target for 83 percent of the state and local development agencies nationwide. It promises, pace Michael Dukakis, good jobs at good wages; the average biotech job pays $50,000 per year, which is twice the national average. More than that, however, it touches at almost every level the hope and the fear with which we've come to face a complicated and dangerous world. It promises to eliminate the diseases like Parkinson's and Alzheimer's that can devastate our families.

It promises to keep us safe from the horrors elsewhere in the world.

he promise is what attracts the people, which is what attracts the money. There are now some 280 biotechnology companies in and around Boston, making the area by far the national leader. According to a recent report by the Massachusetts Biotechnology Council, employment in that one sector of the economy has grown by 10 percent every year since 1996. According to the Cambridge Community Development Department, eight of the top 25 employers in that city are affiliated with the biotech industry. The Boston area gets a larger share of the funding provided for research by the National Institutes of Health -- some $162.3 million in 2000 alone -- than does any other region of the country. Drawn by all of this activity, the pharmaceutical end of the industry has followed the money here.

Besides the Novartis move, described by one industry analyst as an earthquake in the biotechnology industry, Merck, Pfizer, Wyeth, and other pharmaceutical companies also have opened facilities in Boston, and that is not to mention the growth of local pharmaceutical companies like Vertex and Millennium, both based in Cambridge in what researcher Eric Lander has come to refer to as "Genetown," the tight little area in and around Kendall Square. In that one area, which, a decade ago, was the domain of high-tech start-ups, biotech and drug companies now employ more than 25,000 people, and within a mile of MIT, you will find 13 of the 25 largest biotechnology companies in Massachusetts.

Another case study is the Longwood Medical Area, just west of Fenway Park. The area is what has become known as a life-sciences supercluster composed of nonprofit and for-profit institutions, all of them loosely tied in the expanded definition of the biotechnology industry. There are 37,000 people working in the Longwood area alone, an increase of 36 percent over the past decade. There are six colleges within the area and three hospitals. The Harvard Medical School is there -- its research complex still brand new -- as is the Massachusetts College of Pharmacy and Health Sciences. The Dana-Farber Cancer Institute and the Joslin Diabetes Center are cheek by jowl with the CBR Institute for Biomedical Research and the Judge Baker Children's Center.

And into all of these institutions flow the money and jobs coming from what can now be loosely called the biotechnology industry. According to a recent study conducted by the Harvard Medical School, the institutions within the Longwood area with which the school is affiliated accounted for almost $700,000 in National Institutes of Health grants and employed more than 10,000 people. And these people are now part of interinstitutional and cross-disciplinary projects on an unprecedented scale. All this activity has forced the city's political establishment to take note.

In October, the Boston Redevelopment Authority produced a report that calls for the city to develop a strategy to encourage further biotech investment in Boston. The report is glowing in its appraisal of biotech's impact on the city, citing everything from the high-paying jobs to the enhancement of the city's reputation to the fact that biotech jobs are "less traffic-intensive" than jobs in other industries.

"I think that the people who work in biotech are, by and large, people who look at the urban environment as a lifestyle choice," explains BRA director Mark Maloney. "And we already are an intellectual capital, and I think biotech is part of our intellectual capital brand." That's also part of what Harvard president Lawrence Summers was up to across the river.

"We're at a moment of unique potential," Summers says. "From the moment I arrived, I asked the dean of sciences how many people we had doing life-sciences, and he said 640, and I asked over at the medical school how many full-time cancer researchers they had, and they told me 800. The instant they said that, I was amazed at how important these fields were to the entire city." Summers's point man on the project, Harvard professor Michael Porter, told a biotech conference at the Harvard Business School in September that as many as 100,000 new jobs could be attracted here if the region made a concentrated effort to do so.

"Ideas have a gravitational force," explains Lander, the director of the Whitehead Institute's Center for Genomic Research and a key figure in the new Broad Institute initiative. "If you get on the bus in Los Angeles, you'll hear people talk about the entertainment industry. In New York, they talk about the financial industry on the subway, and in Washington, it's the government. Here, you get on the T, and maybe someone's talking about DNA, or biomedicine, or the life of the mind. The Boston intellectual is a young person now who's conversant with biology and with computer science. This is the scientific challenge of the next decade, and the intellectual community for that is here."

"The people who once dined at the Club of Odd Volumes," says Steven Harrison of the Harvard Medical School, "are now working in the labs, or running Millennium [Pharmaceuticals], or sequencing genes."

t's a small world, and Yorgo Modis has covered a pretty big piece of it. His father is Greek, his mother is American, his wife's from Ireland, and he's Swiss. Under "nationalities," his curriculum vitae lists three: Switzerland, Greece, and the United States. He has studied in Geneva, in London, and in Heidelberg. Biotechnology is a field for gypsies -- "We're scientific 'travelers,' " his wife laughs, using the west-of-Ireland term for what the older folks in Galway might call "tinkers" -- and Modis works in Boston now.

Modis is slight, with curly hair and a sneaky smile. He speaks four languages, and he loves to ski and to fly. He's a specialist on the virus that causes dengue fever, a dangerous, mosquito-borne illness that, according to the Centers for Disease Control and Prevention, kills several hundred thousand people a year, most of them children. He also plays the flute with the Trinity Hall Orchestra in Cambridge.

That he passed the Grade 8 level flute examination of the British Associated Board of the Royal Schools of Music, the highest level there is, is right there on his online curriculum vitae along with the seminar he gave in Italy last May on the topic "A Ligand-binding Pocket in the Dengue Virus Envelope Glycoprotein." He's 29 years old, and he loves his work the way creative people do. To listen to him talk about it is to hear a musician talking about a particularly challenging piece or a writer wrestling with a stubborn paragraph.

"The reason it's good is the reason it's hard," he explains. "You're doing what you really want to do -- what your passion is. You're your own boss. You can design your own experiments, and it takes a particular type of person for that to work because that's what makes it hard, too. You're discovering new things, and there's never a guarantee. You can hit a dry patch, and that can be really tough.

"You know, I never really thought about 'being smart.' Especially in this environment, you sort of take it for granted. It seems normal."

Modis is in the fifth (and last) year of his postdoctoral work in a laboratory in the Children's Hospital complex of the Longwood Medical Area. It's a bristling, humming place. The uniform of choice is sweaters and jeans, with an assortment of running shoes that would do credit to the finish line of the Boston Marathon. There are few briefcases to be seen, but there are backpacks slung here and there. Beakers bubble and centrifuges whine, and there's the occasional low grunt of a refrigeration unit adjusting itself. The researchers sit on stools, some of them. Off along one wall is a row of secure computer rooms, and that's where Modis is today. He's studying the proteins that power the virus that causes dengue to penetrate the cellular membrane. Lavender figures on a black screen, the model is a delicate latticework of fitted hexagons.

"When we crystallize the envelope," Modis explains, "we understand not only what protects the virus but what it is that your immune system first sees, which is how your body recognizes the virus, so it's important for us to know what it looks like."

Modis's father was a physicist but, growing up in Geneva, it was biology that first interested Yorgo. He took his degree in London, at the University of Cambridge, in 1995. Looking around for a place to pursue his doctorate, Modis found the European Molecular Biology Laboratory in Heidelberg, a place that bustled with the kind of interdisciplinary approach that has become central not only to research in the life sciences but also to the industry that research has spawned.

In one of his classes, he met Louise Kelly, a brilliant student from Galway. They were married in Clifden, to the north in Connemara, one of those next-stop-Newfoundland spots on the Atlantic. After completing their degrees, they prepared to leave the institute, which, in the interest of institutional dynamism, signs its scientific researchers to terms no longer than nine years. Four years ago, Modis got an offer to work with Harrison at Harvard. He came first. Kelly stayed in Heidelberg to finish her PhD work. He found them an apartment in Brookline.

"Postdocs don't own," he explains. "They rent."

Kelly got a postdoctoral position at the Harvard Institutes of Medicine. In what spare time they had, they went camping, and they skied, and they took a long automobile trip around the country. After a while, Kelly was offered a job with Millennium, a young but well-established pharmaceutical development firm near MIT in Cambridge. The line between academia and industry had blurred greatly over the previous two decades, but Kelly saw it clearly still.

"There was, I guess I would call it a reluctance on my part," she says. "I did think a long time about it. I had no problem with working hard. But I was concerned that, going into industry, I might lose my individuality as a scientist, my creativity." Nevertheless, she took the job, and she's since worked at Millennium on a number of projects, including a recent one involving leukemia.

"I have to say, I've been pleasantly surprised by the quality of the science," she says. "When I was working with leukemia, and I was collaborating with some of the other companies that have become part of Millennium, I got excited about testing drug efficacy."

Because they work in the same field, they share a common vocabulary, and they are sensitive to the demands that work can place on them. "Like tonight," Kelly says, laughing, "he's still in the lab, and I'm here watching television, but I understand the kind of demands that his work can put on him better than most people would, I think."

At the end of this year, Modis will face a decision similar to that once faced by his wife. His postdoctoral work will be complete, and he's going to have to go out and find a job. "I'm looking for an academic position," he says. "Not to teach, but to do research. I want to stay in the lab." But he is part of the biotechnology industry, even if he never specifically works for it -- a rootless place, its boundaries as permeable as the membrane of a cell.

"The dividing line is such a gray area now," Modis says. "For myself, I'd say I didn't work for the industry, but I would say I have a lot more options than I would have had 20 years ago."

here is a stairway at the heart of the Vertex Pharmaceutical complex in Cambridge, a web of refurbished brick industrial properties located across the street from one of George Washington's old gun emplacements at the MIT end of Massachusetts Avenue. The buildings are connected by bridges that look like hallways from the inside, and the hallways look like the hallways in any other young company. They are lined with offices, and there are file cabinets and the odd piece of workstation scattered about in the hallways. And then, you walk up the stairs and through a door, and the laboratory opens up on the other side, all bright and clean and daystruck. The effect is very much like that moment in The Wizard of Oz when Dorothy opens the cabin door to find that someone outside has invented Technicolor.

"It's not a quiet place, no, I wouldn't say that," says Thomas Hoock, a PhD and cell biologist who runs a research team at Vertex. "I think it depends on where you go and on what day."

The staircase leads to other hallways that lead to other laboratories. There's the one with the huge industrial magnet that was so big that they had to lower it into the building by crane through a hole in the roof. And there are even hallways deep in the complex where there is no discernible human sound at all. That's because most of the work being done there -- a project involving kinases, the enzymes that help cells communicate with one another, and their roles in diseases of the human immune system -- is being done robotically.

"It's applying the principles of Henry Ford," jokes Mark Namchuk, the head of the project.

"That's the secret about what Mark's doing down here," replies Hoock. "In his spare time, he's making cars."

The stairway is the key to understanding Vertex. Until you begin to climb it, Vertex might be an advertising agency or a marketing firm. At the top of the stairs, however, is the same kind of place in which Yorgo Modis works -- the same sounds, the same casual dress, the same world entirely. And it says something fundamental about biotechnology (and the people who work in it) that there is a minimal amount of friction between the people who break down the molecules at the top of the stairs and the people who crunch the numbers at the bottom. They even go on company retreats together that are called "Fear and Fun" weekends.

"They want to keep people on the edge," Hoock explains, "so you'll feel like you have to come to work energized just to keep pace.

"Individually, there are a lot of us who like to venture off into corporate, to keep our fingers on the pulse of what people are thinking over in the commercial end of the company and in the executive branch."

It has not been a good week for Vertex, which employs about 500 actual human beings at its Cambridge facility. Shares in the company had fallen 37 percent earlier in the week when Vertex stopped the human clinical trials of a new arthritis drug called pralnacasan when certain animals involved in the research began to show signs of liver damage. A share in Vertex fell nearly $5 in one day. The aftershocks still resonate throughout the place. Even the receptionists talk in hushed tones about the company's financial situation.

"You know, you never like to hear bad news like that, especially as a shareholder," says Hoock, a Chicagoan who came to Harvard and thence to Vertex after graduating from Indiana University in 1987. "But, even so, I have to admit that it's the research that I do on a daily basis that gets me out of bed in the morning. I mean, I'd love to see a good clinical drug come out, but my job is in research."

"A biotech company," says Boger, founder of Vertex, "is a company whose market cap is not driven by sales."

Vertex was famous almost before it was a company, and long before it had produced anything. Founded in 1989, Vertex (and Boger) is the subject of Billion Dollar Molecule, a book by Barry Werth that is a kind of ur-text to the biotechnology boom. The book describes a kind of entrepreneurial Wild West show as Boger and Vertex tumble headlong into scientific discovery and the business of running a business. (The tantrums of the scientists as described by Werth are now the stuff of Vertex legend.) The place has calmed down considerably; nobody's abusing water coolers or cracking up expensive motorcycles in the parking lot anymore. But the undisputed star of the book -- and the company -- is Boger, a renegade PhD who left pharmaceutical giant Merck to strike out on his own.

"I decided [to found my own company] for a number of reasons, chief of which was that I discovered that I was not going to live forever," Boger says. "I realized that time mattered. I got to the age where time seemed less of a philosophical construct."

Boger made his mark as the classic biotech entrepreneur -- equal parts scientist and salesman -- and neither the scientific end nor the business end of Vertex can long survive if the other collapses, which is the great vise within which all biotechnology companies operate. They are not designing revolutionary widgets for use in sophisticated plumbing. They are designing products that will work in the human body -- a stubbornly unpredictable mechanism.

"Humans are complex systems," explains BioVentures' Goldberg. "The results you get back are rarely ever black and white. They're always equivocal, so you have to go back and do other steps. If you're not a huge company, equivocal results are problematic."

e are still a city of neighborhoods. We had original neighborhoods formed by geographic necessity, and immigrant neighborhoods formed by demographic imperative, and economic neighborhoods that grew up around the old muscle industries. This is a new thing we have here, though, along Longwood Avenue west of the ballpark and in Genetown in Cambridge. There are new restaurants and late-night bars, and coffee bars catering to those who have spent all night in the lab.

"I think it's a neighborhood, but I don't know if it's a classic one," says the BRA's Maloney of the Longwood Medical Area. "It's a 24-hour neighborhood in the way that many of our classic neighborhoods aren't. The people who work there are looking for breakfast at dinnertime.

"Also, there's numbers of people who are tourists to that area -- the patients. It's an enormously different kind of population."

And there is another neighborhood, too -- a less easily defined one that encompasses Yorgo Modis's lab and the offices of Vertex in Cambridge. The people who live there are young and passionate, and their interests are not confined to one job or even one field of concentration. The new Boston is a borderless neighborhood of the mind.

"It's almost too big," says Louise Kelly. "In Heidelberg, where we lived before, it was so small that it actually was a community where you knew everyone. It's not like that here."

As has always been the case, the industry that defines the area defines the intellectual and cultural climate, and it sets the parameters for the public debate. In Colonial Boston, the shipping industry inevitably channeled the region into the debate over complicity in the slave trade and, eventually, into abolitionism. Heavy industry forced the questions of unionization and workers' rights in the mills, and the questions of immigration in the city's politics. To commit a city to a specific industry means always to commit the city's other institutions to cope with everything that the industry produces. Now, though, to commit to biotechnology on a grand scale is to commit oneself not only to the cutting edge of modern science, but also to commit the city's intellectual culture and its politics to grappling with questions as fundamental and profound as the definition of what is human.

There is about biotechnology a kind of messianic aesthetic; as Robert Teitleman wrote in Gene Dreams, his seminal account of the industry's early days, "Selling [biotechnology companies] was not that much different from selling, say, a painting by Warhol. . . . The latter-day entrepreneur carried the aesthetic culture into the society of business. Without products, distinctions become a matter of opinion." And there always has been more than a little creative hubris to the aesthetic culture of this particular business, which keeps biotechnology both in a paradoxical place as an economic engine and on the emerging frontier as regards the moral and ethical impact on society of the products the industry produces.

The Brookings Institution study released in October states that biotechnology research and development -- on which, so far, the overwhelming emphasis of local biotechnology has been placed -- is "uncertain, time-consuming, and expensive." The study also found that "relatively few research projects lead directly to new products." The Brookings report cites the fact that about 400 biotech medicines are in development, but that only 100 biotech medicines have made it through to the market in the past 30 years.

"To date," the report concludes, "even successful biotechnology clusters have produced only modest returns to their regional economies. . . . In the two largest concentrations of biotech activity in the nation [Boston and San Francisco], none of the largest biotech firms is among either region's 25 largest private employers."

"The difference is easily seen if you look at biotech versus high tech," says Joe Cortright, an economist with Impresa Inc. in Portland, Oregon, and the co-author of the report. "What's driven the importance of high tech within the economy is that, basically, we can cram twice as many transistors onto a chip now, and that's what they've been doing for 30 years. Biotech, despite the huge advances in the science, is not producing things that are cheaper than what they replace. It takes a long time and a lot of money to produce those products."

Harvard's Summers sees the solution for this problem as an integrated and diverse biotechnology strategy that includes not merely research but production as well, and is based on Boston's undeniable and permanent advantages in terms of its universities and its hospitals. "The challenge," he says, "is to keep the lead we have in the life sciences better than we did the lead that we had in high technology and computers. It can't be our goal to set up one strategy to serve the biotech industry. We have to follow a great many approaches, and whole sets of individual researchers, because we can't know where the next breakthroughs are coming from."

Once those products emerge, they will do so into a new and roiling public debate. Biotechnology has raised a host of issues -- from embryonic stem-cell research to bioterror to the safety of genetically engineered foodstuffs -- that will dominate the political and social landscape for the foreseeable future. In October, the President's Council on Bioethics released a comprehensive report titled "Beyond Therapy: Biotechnology and the Pursuit of Happiness." There is very little actual science in the report; it primarily deals with the ethical and moral consequences of what it tacitly admits is the headlong momentum of the current biotechnology moment.

At one point, for example, the report cites "the failure properly to appreciate and respect the 'giftedness' of the world. Acknowledging the giftedness of life means recognizing that our talents and our powers are not wholly our own doing, nor even fully ours, despite the efforts we expend to develop and to exercise them. It also means recognizing that not everything in the world is open to any use we may desire or devise."

The arguments of this report -- which, after all, was prepared to inform the thinking of a politician -- occasionally are so removed from the science of biotechnology that it becomes clear that a great deal of the future debate on the issues of biotechnology might well be composed of scientists and moral philosophers talking past each other, with politicians in the middle trying to mediate the discussion. Nevertheless, the report is correct when it argues that a wide-ranging debate on biotechnology now informs public policy and society in general the way a new industry always does, except that the stakes are immeasurably higher here. For their part, the scientists agree.

"The industry has to engage public officials in this debate about is it safe to make a genetically engineered human," says Dennis Selkoe, a prominent Alzheimer's researcher. "Let's say, in terms of putting in an enzyme that degrades amyloid-beta [the protein thought by many to cause Alzheimer's disease]. Who's to say that should be done or shouldn't be done? I'd say it has to be the public officials."

These are the questions that they talk about at Vertex, in addition to designing drugs and mapping out marketing campaigns, and they are the questions that Yorgo Modis and Louise Kelly talk about over late dinners in their apartment in Brookline, and they are the questions that arise from Mel Feany and her fruit flies. All their texts are living things.

Charles P. Pierce is a member of the Globe Magazine staff.

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