Wanted: Collaborative life-scientists for drug discovery

The golden age of drug discovery is over—at least for now. Over the past 10 years or so, a number of highly profitable drug patents have expired, and the blockbuster drugs of the 1990s have proved hard to replace. The pharmaceutical industry, which once made billions while transforming lives, has been forced to change how it operates. From megamergers and offshoring to the dramatic restructuring of R&D departments, pharma has become a very different employer.

In such a rapidly shifting industry, it’s hard for anyone to keep tabs on employment opportunities; weary and overwhelmed by experiments, graduate students and postdocs can find themselves completely overmatched.

It is easy to feel despondent when, in the United States alone, the pharmaceutical industry has shed more than 300,000 jobs since 2003, according to Challenger, Gray & Christmas. Yet, even as redundancies continue to make headlines, there are openings for aspiring biotech and pharmaceutical scientists. Those opportunities, though, may not be where they used to be, nor are the risks, incentives, and demands early-career scientists face the same as those of a decade ago.

Who will emerge as the major drug discoverers in the next decade? How can you join their ranks? Science Careers asked scientists from industry and academia to offer tips for those looking to enter the job market in the coming years.

The new world of pharma

One of the most important drivers of change in the pharmaceutical industry was a wave of patent expirations that really picked up steam in 2010. Employees felt the impact of this a decade before, as companies anticipated the drop in profits. By the end of 2012, three dozen of the world’s top brand-name drugs had lost patent protection, paving the way for cheaper generic versions. The ensuing competition among drug companies is estimated to have eroded 90% of top drug companies’ annual U.S. sales.

To make up for these losses, the larger pharmaceutical companies sought savings by cutting R&D departments, which traditionally have eaten up a big chunk of the industry’s spending. To compensate, companies, in effect, outsourced early-stage research to smaller specialty pharmaceutical and biotech companies.

The result: Startups are the big recruiters now, says Richard Bozzato, a senior adviser for MaRS Discovery District in Toronto, Canada, a nonprofit that aims to foster relationships between scientists, venture capitalists, and industry. Oncology and neuroscience are the fields most actively hiring, he adds.

David Lowe, CEO of Aeglea BioTherapeutics, a 1-year-old company based in Austin, Texas, agrees that startups are where the jobs are. Lowe, who took his first job with Genentech in San Francisco, California, almost 30 years ago, when it was still a relatively small company, says that companies today have a different set of needs than when he began. Much of today’s drug discovery focuses on biologically sourced drugs as opposed to chemically synthesized ones.

Because many of the new drugs are ‘biologics,’ developed from the cells of microorganisms, plants, and animals, today’s industry is recruiting more life scientists. “No one studies entomology anymore,” but entomology could be hugely valuable to drug discovery, Lowe says.

Be collaborative and interdisciplinary

Another trend: Small companies are looking for collaborative scientists. Collaboration is “anathema to a lot of scientists, particularly young ones,” Lowe says. In graduate school, “you are supposed to be chief cook and bottle washer on all your own stuff.” Most graduate students are still trained to work independently, to value ownership of their work that leads to primary authorship on articles published in prestigious journals—a major key to success in academia. Scientists employed at large pharmaceutical companies traditionally worked in silos, too, but collaboration is essential for those who wish to thrive in the startup environment.

George Georgiou, a chemical engineer at the University of Texas, Austin, says that industry values people who are not just collaborative but who can work in an interdisciplinary way. Georgiou has mentored 48 students since setting up his lab in 1986; 12 of them have ended up in the industry. He attributes this success, in part, to running a diverse group including chemists, biochemists, molecular biologists, and chemical engineers—and encouraging his team to have a healthy respect for all those disciplines. The result, he hopes, is students who aren’t intimidated by other fields and who understand the jargon used in those fields.

Another advantage of working with such a mixed group is that students have a better understanding of the whole drug-development pipeline. “What I think distinguishes my students from those of other labs is that my students understand not just whether a molecule does what it is meant to do, but … how one might manufacture it,” Georgiou says.

Risks and incentives

Working in Georgiou’s lab was good preparation for industry, says Tom Van Blarcom, a research scientist with Rinat Laboratories in San Francisco, California. Van Blarcom earned a Ph.D. in chemical engineering in 2008 and took a position at Rinat, which develops protein-based therapeutics; Rinat was acquired by Pfizer in 2006 but was allowed to keep operating as an independent biotechnology unit. Van Blarcom was attracted to industry because of the speed with which he could get things done there. “I don’t have to prepare my own media [or] pour my own plates,” he says, nor does teaching cut into his research time. Another advantage of industry, Van Blarcom says, is that young scientists there have access to a larger number of mentors.

Industry also means more diverse employment opportunities for scientists, including for two-scientist couples, as long as they’re willing to settle near a pharma-biotech hub. “I didn’t want to end up somewhere where there [was] only one fulfilling career option in town,” Van Blarcom says—so he and his partner, Diana Van Blarcom, settled in the San Francisco Bay area, a hotbed of pharma and biotech companies, including many startups.

That’s important because layoffs are part and parcel of the new pharmaceuticals industry. “It’s rare for someone to stay at the same company for their entire career,” Van Blarcom says, and there is security in knowing that there is probably another opportunity close by.

Got the skills, get the job

Van Blarcom believes that his interviewing technique helped him get the job. “When I showed up to my interview I was very prepared,” he says. He had read a handful of papers from each of the people he hoped to meet with, so he could converse about their work in more depth. Coming from Georgiou’s lab also helped him, he thinks, because Georgiou’s work is known for having a strong therapeutic bent: With 29 issued patents, more than half licensed to pharmaceutical and biotechnology companies, Georgiou has close ties with industry. “Having that track record from my [graduate adviser] definitely got my foot in the door,” Van Blarcom says.

At Rinat, Van Blarcom focuses on designing, building, and using sequence libraries to discover more effective antibodies. These libraries consist of sequences based on antibodies found in hundreds of people; Van Blarcom uses his bioinformatics knowledge to curate this data. “People could really have a leg-up on the competition if they are proficient in R or Perl,” he says. New sequencing technologies are generating so much data, he says, that automation is becoming essential, so suitable coding skills are becoming indispensable.

An implementation impulse

Van Blarcom says the decision to join Rinat instead of pursuing a university position was philosophical. He sees industry as a place to “produce tangible results,” while academia is more a breeding ground for big ideas. “I never thought I was the type of person that would come up with ground-breaking ideas; I was more of an implementer, so [industry] seemed to be … a natural fit for me.” In industry, he says, success is unlikely to come in the form of a Nature or Science paper but as a chance to develop a drug that ends up helping patients’ lives. “[That’s] ultimately a lot more powerful than another publication,” he says.

Job Change Lands Egyptian Scientist in Legal Battle

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Rania Siam thought she was putting her troubles behind her when she left Misr University for Science & Technology (MUST) near Cairo. It was June 2005, and the microbiologist had spent four tumultuous months as a lecturer there, quarreling with administrators and fellow faculty over working conditions and research support. That September, she landed a tenure-track position at the American University in Cairo (AUC). But just when things were looking up, MUST sued her.

In what observers call an unprecedented case in Egypt, MUST claimed that Siam’s departure caused “damage to MUST’s reputation and its scientific credibility,” and “lost [MUST] the scientific and educational benefits, which [it] would have gained from [Siam’s] research.” MUST took particular umbrage at missing out on a grant that Siam had applied for during her brief stay at the university and demanded $3 million in damages.

After 9 years of legal maneuvering, an Egyptian judge in March ordered Siam to pay MUST $49,000—the sum of the forfeited grant—in addition to court and attorney fees, and more than $14,000 in damages. Last week, Siam filed an appeal with the Court of Cassation, Egypt’s highest judicial authority.

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Journal Editors Get Twitter-Savvy

Science journal editors are the air traffic controllers of the science world. Their task is to guide reports of original research through a process of peer review and revision and deliver it quickly and clearly to its intended audience, all the while keeping an eye on what else is in the air. It’s a hard job, and the challenges are changing as a result of the Internet, the globalization of science, and social media. Here, we describe the challenges and changing roles of science journal editors as they embrace digital technologies in their efforts to stay abreast of scientific trends and controversies.

The traditional role of science journal editors

These days, most science journal editors earn a Ph.D. and do a postdoc before moving into scientific publishing. Once they’ve jumped the academic ship, they learn on the job. When they are not out visiting scientists or attending conferences to recruit new papers, they are in their offices reading scientific manuscripts and corresponding with authors, fellow editors, and current and potential reviewers.

Science Journal editors must be able to read and understand a scientific manuscript and form a preliminary opinion of its relevance. Then they must corral opinion on the novelty, rigor, and scientific interest of a reported new result. Reviewers’ opinions are often at odds, and their analyses may vary, so editors are charged with collecting, distilling, and evaluating those analyses. Science journal editors make recommendations—and sometimes a final decision—on whether or not to publish.

Once a paper is accepted, editors work with the authors to improve the manuscript and make the suggested revisions—a task that requires patience, interpersonal skills, and the ability to achieve consensus among opinionated scientists.

Science journal editors in the age of social media

Twenty years or so ago this process was managed mostly on paper, but over time it went electronic and—thanks largely to email and online manuscript submission systems—became quicker and more interactive. Now the role of science journal editors is changing again. As social media facilitates one-to-many interactions, editors are finding new ways to maintain their networks and eavesdrop on the scientific community. Twitter is emerging as the preferred tool among science journal editors for meeting the changing demands of their job.

Nicholas Wigginton, Science’s Ann Arbor, Michigan-based earth and environment editor, says that one of the biggest challenges for editors is “to keep in touch with new scientific communities” as science’s global reach expands. Wigginton employs Twitter to cultivate and maintain a network of potential reviewers in countries that once were poorly represented in academic journals but, because of significant improvements in the quality of their research, are attracting fresh attention.

By listening in on online conversations, editors also use Twitter to keep up with the latest news from their field. “[Twitter] is replacing the role of listening in to chatter in the hallways of conferences,” Wigginton says. Increasingly, researchers are tweeting the key points of their colleagues’ talks at scientific meetings. By following a meeting’s hashtag, editors can learn about new results and gauge the researchers’ responses without being in the room. Editors can’t be everywhere at once; even a major journal like Science has only about 30 editors, too few to make it to all of meetings and conferences that take place every year.

Jake Yeston, Science’s deputy editor for physical sciences, who is based in Washington D.C., says, however, that schlepping to a city and sitting in a room listening to science remains very much a part of his job as an editor. Twitter, he says, is useful but imperfect: The danger is that you’ll hear the most vocal people and miss what the broader community is saying. “You get a really good sense of what those 10 people think, but that isn’t what is happening in the field as a whole.”

Sacha Vignieri with her son Griffin Ream (left) and Sceloporus occidentalis (center of face).
Twitter is especially useful, Yeston says, for following high-profile flops. “It is kind of like jackals; when there is a paper that kind of looks like it is going south, then people attack it,” he says. Editors may have papers under review that rely on a published result; if it’s being called into question, editors need to know about it, he adds.

Yeston says he avoids tweeting about particular papers, because he assumes that, as a Science editor, he’s on stage: He worries he may give scientists the wrong impression about the types of papers he is interested in reviewing. But that doesn’t mean that editors wish to remain invisible; some use Twitter and other social media tools to build and maintain a public profile. Sacha Vignieri, Science’s Portland, Oregon-based ecology editor, says that many editors want to be accepted as scientists’ peers. By creating an online presence, they are better able to demonstrate their fluency in the areas they cover and show that they were once active researchers in those fields. The value of such an online presence remains a topic of ongoing discussion, she acknowledges, at Science and other journals.

Editors increasingly use social media to reach out beyond the usual specialist audiences. Editors are under increasing pressure to ensure that the science in their journal is accessible to nonspecialists, explains Michaela Handel, The Journal of Experimental Biology’s publishing editor, who is based in Cambridge, United Kingdom. She spends more time on public outreach today, she says, than she has at any other time during her 17 years as an editor. She uses Twitter, Facebook, and YouTube for her outreach. “It’s a great way of telling our community what we are doing,” she says.

Focus on fundamentals

Despite the advantages it offers, Twitter hasn’t really changed the daily responsibilities of a journal editor, except around the edges. “I don’t think social media is really something people should be thinking about when they consider becoming an editor,” Vignieri says, although “it’s kind of an interesting add-on.” Applicants are not vetted on their social media skills, she adds.

What is still most necessary for aspiring editors is a broad and detailed knowledge of the field and the skills needed to refine a piece of scientific work and shepherd it through to publication. At its heart, scientific editing is still about publishing a field’s most interesting and influential papers, which means that reading, writing, and thinking about science are still at the core of the job, says Cell Stem Cell editor Deborah Sweet, who is based in Cambridge, Massachusetts. (She is also the publishing director at Cell Press.) Those activities are likely to remain the mainstay of the work scientific journal editors do, even as new technologies alter the job in significant ways. If mastering and practicing these skills is an attractive prospect, a career as a journal editor might be for you.

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The EcoIsland

The UK’s energy prices are soaring. As gas and oil reserves run dry, the cost of energy will continue to climb. But what if we could wean ourselves off fossil fuels and make the jump to clean, renewable energy?

This is exactly what a small island off the coast of Africa plans to do. With a population of 11,000 people, El Hierro is building a solution to its mounting energy costs. As the most remote Canary Island, it struggles to meet the high price of shipping oil from the mainland. But what the island lacks in fossil fuels it makes up for in wind – over 3,000 hours a year of gusts blowing fast enough to propel windmills and generate
electricity.

And on the rare windless day, El Hierro hopes to bridge the gaps in its electricity supply with the ultimate energy cache: a 500,000m cubed reservoir some 700m up inside the island’s dormant volcano. When the power supply dwindles, the reservoir
can be drained downhill through turbines to generate electricity.

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Loosing the Louse on Europe’s Largest Invasive Pest

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Don’t be duped by its delicate pale flowers; Japanese knotweed can be a sinister plant. Native to eastern Asia, Fallopia japonica was intentionally introduced into gardens in Europe 200 years ago by fans of its attractive blooms; from there it spread to North America. What makes this invasive weed so menacing is its ability to grow through solid concrete foundations, forcing contractors to abandon infested building sites. In England alone, about a half-million homes are uninsurable, and in the United Kingdom, damages and removal cost $288 million a year.

Now the British government has taken a bold step to solve this knotty problem, and North American researchers might not be far behind. Last week, after more than 5 years of research into the matter and an initial pilot trial, the United Kingdom approved the widespread release of one of the plant’s natural enemies. While there are dozens of biological controls already in use against insect pests, this is the fi rst offi cially sanctioned release of one against a weed in the European Union. “This is an extremely important step. … If this is successful, it will really open the doors and open the minds of people for this control method in Europe,” says weed biocontrol specialist Hariet Hinz of CABI Europe in Delemont, Switzerland, a nonprofi t agricultural research organization.

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May the Best Analyst Win

LAST MAY, JURE ŽBONTAR, A 25-YEAR-OLD computer scientist at the University of Ljubljana in Slovenia, was among the 125 million people around the world paying close attention to the televised finale of the annual Eurovision Song Contest. Started in 1956 as a modest battle between bands or singers representing European nations, the contest has become an often-bizarre affair in which some acts seem deliberately bad—France’s 2008 entry involved a chorus of women wearing fake beards and a lead singer altering his vocals by sucking helium—and the outcome, determined by a tally of points awarded by each country following telephone voting, has become increasingly politicized.

Žbontar and his friends gather annually and bet on which of the acts will win. But this year he had an edge because he had spent hours analyzing the competition’s past voting patterns. That’s because he was among the 22 entries in, and the eventual winner of, an online competition to predict the song contest’s results.

The competition was run by Kaggle, a small Australian start-up company that seeks to exploit the concept of “crowdsourcing” in a novel way. Kaggle’s core idea is to facilitate the analysis of data, whether it belongs to a scientist, a company, or an organization, by allowing outsiders to model it. To do that, the company organizes competitions in which anyone with a passion for data analysis can battle it out. The contests offered so far have ranged widely, encompassing everything from ranking international chess players to evaluating whether a person will respond to HIV treatments to forecasting if a researcher’s grant application will be approved. Despite often modest prizes—Žbontar won just $1000—the competitions have so far attracted more than 3000 statisticians, computer scientists, econometrists, mathematicians, and physicists from approximately 200 universities in 100 countries, Kaggle founder Anthony Goldbloom boasts.

And the wisdom of the crowds can sometimes outsmart those offering up their data. In the HIV contest, entrants significantly improved on the efforts of the research team that posed the challenge. Citing Žbontar’s success as another example, Goldbloom argues that Kaggle can help bring fresh ideas to data analysis. “This is the beauty of competitions. He won not because he is perhaps the best statistician out there but because his model was the best for that particular problem. … It was a true meritocracy,” he says.

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Ancient Tweaking


Twenty years ago, scientists knew nothing of the scraps of RNA that are now known to influence just about every process in our bodies. Back then, the textbooks were simpler: genes code for proteins via the intermediate of RNA, and proteins called transcription factors regulate other proteins. This recipe was so entrenched in the basic orthodoxy of molecular biology that it was even given the name ‘the central dogma’ by the co-discoverer of DNA, Francis Crick.

Scientists now know, however, that this classic view of protein regulation is far too blunderingly inefficient for evolution to settle for. At some point hundreds of millions of years ago, the generation of a small stretch of RNA that could tweak this process gave an individual the edge over everyone else. And so regulatory RNA was born. These scraps of RNA – on average only 22 nucleotides long and now dubbed microRNAs, or miRNAs for short – bind to some messenger RNAs and label them for inactivation or destruction.

So far thousands of miRNAs have been identified in animals. These superintendents of protein regulation are involved in the earliest stages of an animal’s development, determining which cell types grow where and when, and how these cells differentiate into the different body parts. However, since the discovery of miRNAs, many scientists have wondered whether the same miRNAs govern specific tissues in different animals. Knowing this would not only give clues to the age of these different miRNAs, but
also to the age of the cells in which they are found.

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Shaping up HIV

In the 1960s, a Danish company, seeking to improve on the traditional football made from the bladder and stomach of animals, invented the modern football. The designers realised that to form a perfect ball they needed to combine 20 leather hexagons with 12 pentagons, and in so doing demonstrated one of the basic laws of shape – that you cannot wrap a sheet of six-sided hexagons around a sphere. To induce the sheet to bend, the company had to introduce five-sided pentagons alongside the hexagons.

On the micro scale, the human immunodeficiency virus (HIV), which causes AIDS, faces a similar challenge during the assembly of new viral particles: how to coerce its hexagonshaped building blocks to form the spherical envelope that
surrounds its viral innards. Lifting a page from the football manual, structural biologist John Briggs, group leader at EMBL Heidelberg, wondered if HIV likewise solved this shape conundrum by introducing pentagons between the hexagons.

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Cue factors

Our genes were once thought to be responsible for shaping who we are. But now scientists are having a rethink. Thanks to a glut of data from new sequencing projects, researchers are beginning to recognise that the regions of the human genome that encode proteins are unlikely to be behind the millions of differences between people.

So the question remains: what accounts for these differences? Searching for an answer, biologists have pored over the few individual genome sequences that have been completed so far. And these researchers have asked: if the rare stretches of DNA that code for proteins are not responsible for many of the differences found between humans, then what about the remaining 98% of the genome that does not encode proteins – the so-called non-coding DNA?

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