A year and a half ago, Jean-Jacques Garaud, who heads pharmaceuticals research and early-stage drug development at Roche Holding in Basel, Switzerland, bumped into an old friend at a dinner party near the Place des Vosges in Paris — kidney specialist Gérard Friedlander, who’d been a fellow intern at Claude Bernard Hospital in the French capital back in the late 1970s. At the time of the dinner, Friedlander was doing innovative research at the Paris-based Necker School of Medicine into the way calcium and phosphate are transported by the urinary system, and Roche was seeking outside experts to work with its in-house scientists.
“I said we should talk together,” recalls Garaud, who specializes in internal medicine and infectious disease. And voilá! Friedlander — though still at Necker — is now collaborating with Roche in studying the biology of kidney disease.
“I don’t want to give the impression that the only way we are managing our science is by having dinner with friends,” Garaud is quick to point out. Still, Roche researchers and executives are trawling the web, professional meetings, university journals and their own Rolodexes in search of cutting-edge academic experts who can bolster the $52 billion manufacturer’s labs and help it develop drugs for cancer, neurologic diseases, inflammatory disease and other ailments. For instance, another bit of networking by Garaud — based on a decadelong professional friendship with Jean-Claude Tardif, director of the Montreal Heart Institute’s research center — led to a program for joint research into coronary disease at the Canadian institute about three years ago. That undertaking has since burgeoned into several projects, one of which is in late-stage clinical trials. And Roche is working with scientists at Baylor Institute for Immunology Research in Dallas on autoimmune diseases and immune response to chronic viral infections.
Garaud is right, of course, that all this outreach isn’t just a matter of dinner parties. Nor are Roche and other big drug companies merely collecting some nice extra tidbits of research to fill in temporarily for their own underperforming labs. These examples are the first signs of a major shake-up of what was once a powerful industry of vertically integrated giants.
“It’s not a productivity crisis for the industry,” says Kenneth Kaitin, director of Tufts University’s Center for the Study of Drug Development. “It’s a business-model crisis.”
By now, the drug industry’s problems are all too well known. With their research labs faltering, the major pharmaceuticals companies — known as Big Pharma — have tried merging with each other, buying up biotechs and waiting for the new science of genomics to produce miracles. None of that has worked, so executives like Garaud are trying more-drastic measures. Perhaps the science is too sophisticated, the research too expensive, the trials too complex and the customer base too diffuse for a single company, no matter how big, to do everything by itself.
Thus the pharmaceuticals makers are experimenting with a variety of new business models, almost the same way they experiment with molecules, hoping to find a blockbuster that will save their bottom line. Increasingly, they are turning to outsiders to take on all sorts of tasks, even ones that have traditionally been seen as essential, ranging from early-stage research to animal trials, human trials, data analysis, regulatory submissions and marketing. They are collaborating with universities, and with other companies, to a degree and depth never done before. At the same time, some companies are expanding beyond prescription drugs into more-lowbrow areas such as animal health and over-the-counter potions.
“If you look at the endgame, which is the introduction of new products, there has been a decrease of productivity in the past 15 years,” Garaud says. “Paradoxically, it is happening at a time when we are witnessing the most fantastic revolution in life science and technology.” The upshot, Garaud says, is that he and his colleagues must do better at choosing targets and sharing the risk.
“For the last 20 years, [Big Pharma] built huge infrastructures and had huge wins on the short term,” adds Ian Wilcox, head of life sciences at Hay Group, a Philadelphia-based consulting firm. “Now that business model requires an investor risk that is becoming untenable.” But the rejiggering raises some troubling questions about the very definitions of pharmaceutics and drug companies. Now that they are shedding so many drug tasks and taking on so much nondrug work, it seems inappropriate to call them drug companies. It’s not even clear if they share a core competency. “A lot of large companies are looking at themselves as holistic health care companies,” says Terri Cooper, a principal at Deloitte Consulting in New York.
The litany of woes starts with patent expirations, when blockbuster drugs lose their exclusive marketing rights, allowing cheaper generic versions to flood the drugstores. Pfizer’s Lipitor, the top-selling drug on the planet, will hit that dreaded milestone in November, and 2012 will usher in a record $44.6 billion in expirations, according to New York–based drug research firm Mehta Partners, including those of Pfizer’s Viagra, AstraZeneca’s Seroquel for schizophrenia, Bristol-Myers Squibb Co.’s anticlotting superstar Plavix and Merck & Co.’s asthma and allergy medication Singulair. The good news is that the hemorrhaging dries up after next year. From 2013 through 2015, Mehta forecasts only $13 billion to $24 billion in patent losses annually.
One question mark is how quickly generics makers will be able to jump in with equivalent biologic drugs, or drugs made from living cells. The science for making such drugs is much more complex and delicate than for copying traditional chemical-based drugs, because living material like cells can be affected by even small changes in factory conditions. Last year’s health care reform included rules that were supposed to speed up the legal and regulatory pathway for these generics by setting a time limit on brand-name biologics’ patent exclusivity. However, lobbyists and lawmakers are now debating how to define “exclusivity.” And the science hasn’t gotten any easier.
In any case, patent deadlines themselves don’t have to be disastrous. “Patent expirations are a normal part of life,” points out Michael Krensavage, who runs New York–based Krensavage Asset Management, a hedge fund firm specializing in pharma. (He won’t reveal his firm’s asset size.) “The problem is if you don’t have drugs to replace them.”
That, indeed, is a problem. U.S. companies have been regularly spending 19 to 20 percent of domestic annual sales — a total $67.4 billion last year — to try to produce these replacement drugs, according to the Pharmaceutical Research and Manufacturers of America, or PhRMA, the industry’s trade group. However, that money buys less and less. Tufts now pegs the average cost of developing a new drug at $1.3 billion, up from $800 million a decade ago. In that same decade an annual average of 30 applications for innovative new drugs has been filed with the federal Food and Drug Administration’s Center for Drug Evaluation and Research (CDER), nowhere near the high of 45 reached in 1996.
“Productivity has gone down 9 to 11 percent per year for years,” says Peter Tollman, a senior partner in Boston Consulting Group’s health care practice.
The main explanation for that slowdown is that the easy discoveries — understanding the most clear-cut disease processes, like high blood pressure — were achieved long ago. As Roche’s Garaud puts it, “We are getting into territories that are more uncharted.”
The mapping of the human genome was supposed to be the answer. The basic idea was to sequence, or identify, the exact order of the 3 billion pairs of chemical units that provide the basic genetic instruction for human development. In theory, scientists could search for unusual genetic variants that seemed to occur in people with particular diseases and then develop the medical equivalent of dart guns precisely targeted at those variants. The first draft of the genome was announced in 2000 and completed in 2003, but the research has been slow to lead to viable products. The causes of most diseases, it turns out, are much more complicated than a couple of obvious genetic mutations.
A few gene-based matches have been made, most recently GlaxoSmithKline’s and Human Genome Sciences’ Benlysta, a drug for the autoimmune disease lupus that was approved by the FDA in March. Experts expect that autoimmune diseases and some cancers, along with diagnostic tests, will continue to be the main beneficiaries of genomic discoveries in the near term. But there’s a wide range of opinions, from optimism to cynicism, about how quickly this scientific work will turn into actual treatments and how many there will be.
One crucial tool that could speed up this trend is lower-cost sequencing. As more scientist-entrepreneurs compete to sell gene-sequencing machines and personalized genomes for the mass market, the cost of sequencing has already dropped from $2.7 billion for the first genome down to $5,000 per person or even lower, depending on who’s bragging. Tony Butler, senior health care analyst at Barclays Capital, thinks the holy grail of a thousand-dollar genome could be achieved in less than three years; science writer Kevin Davies, in a book published last year and appropriately titled The $1,000 Genome, predicts that achievement this year. Such price discounting is important, Butler points out, because genomics-based medicine “is going to require sequencing a lot more individuals, and we can only do that by lowering the cost.”
Once they come up with a promising product, companies must get the FDA’s approval. The picture there is actually not as gloomy as most industry watchers assume. True, even the FDA admits that its standards have grown more demanding in recent years. According to PhRMA, the number of procedures required for an FDA-sanctioned clinical trial has increased 68 percent since 1999, from 96 to 158, while the length of a typical trial has shot up from 460 days to 780.
Most observers see this as just the newest turn in the agency’s historical boom-bust cycle. It goes like this: Patients who’ve been taking drugs already on the market start to suffer serious side effects, there’s a public outcry, Congress demands an investigation into the FDA’s drug-review system, and the FDA gets more cautious about approving applications. After a few years of slow approvals, other patients start asking why they can’t get medications that are available in Europe, Congress holds more hearings, and the FDA speeds up. “The FDA is a reactive, conservative bureaucracy, and they are simply reflecting the concern about drug safety,” says Kris Jenner, who manages T. Rowe Price’s $3 billion Health Sciences Fund mutual fund. The agency has been in “slow” mode since Merck pulled the painkiller Vioxx off the market in September 2004 because of serious risks of heart attacks and stroke. This caution has only been reinforced by a slew of safety problems from other companies’ drugs plus 18 congressional hearings.
However, Janet Woodcock, the director of the FDA’s drug review center, insists that science, not politics, is pushing the bar higher. “We learn new science, and then an [added] evaluation has to be done,” she says. For instance, when patients with multiple conditions are taking chronic drugs, “we need to look more carefully,” she says, to see if common events like heart attacks are more frequent. But Woodcock, a rheumatologist by training, says the agency is also making it easier to get drugs approved, with new policies on early-stage trials that allow varying sets of doses in people and animals.
Over the past ten years, manufacturers havesought new drugs as much in one another’s labs as in their own. Thanks to a rash of mergers, there are now just nine or ten Big Pharma names, depending on how strict the definition is — half as many as there were in 1999. Pfizer, most famously, sucked up Warner-Lambert, then Pharmacia (both of which were the products of earlier nuptials) and then Wyeth. Meanwhile, Hoechst and Rhône-Poulenc became Aventis, which was subsequently bought by Sanofi; Merck took over Schering-Plough Corp.; and Glaxo Wellcome married SmithKline Beecham. Experts say these linkups generally succeed in trimming costs by reducing overlap, closing sites and cutting jobs. Merck expects to save $3.5 billion annually from its 2009 merger with Schering-Plough starting next year, and Pfizer forecasts a savings of $4 billion a year from its 2009 acquisition of ?Wyeth. But the deals rarely boost R&D productivity and can hurt morale.
For good or ill, that escape route is about to disappear, because there are few companies left to merge with. “I don’t think you’ll see a merger amongst the top eight or ten [drugmakers], given their size and antitrust considerations,” predicts Philip Pfrang, a New York–based Deloitte partner who specializes in M&A. That still leaves a juicier pool of fish: the small and medium-size biotechs that have been outproducing the big companies. Although the FDA doesn’t track applications by size or type of company, Woodcock says that anecdotally, “we’re seeing more and more of the drugs that we approve from small companies,” and virtually all industry observers agree. Over the past half dozen years, the biotech buys have ranged from Roche’s $46.8 billion purchase of Genentech in 2009 to Schering-Plough’s acquisition of ??NeoGenesis Pharmaceuticals, a Massachusetts biotech specializing in antivirals, for $18 million in 2005.
But even gobbling up biotechs isn’t enough anymore. The science has gotten so complex that it requires the most advanced minds in the ivory tower. And the cost has gotten so high that it requires more wallets. That’s where the new business model starts to kick in.
The most widespread trend involves boosting the role of outside scientists, particularly from academia. Universities, independent research labs and the National Institutes of Health have traditionally handled the earliest-stage work of understanding basic biological processes, such as the structure of proteins. Now, however, Big Pharma is counting on them to cooperate in the next stage, known as translational science, which uses the basic research to seek molecules that are effective against specific disease targets. This could even include human trials.
Some companies are doing this by financing next-stage research at universities, like Roche does with the Necker School, Baylor and the Montreal Heart Institute. Roche now has programs at approximately a dozen institutions around the world, usually seeding several projects at each site with “money or in-kind support,” Garaud says. Similarly, GlaxoSmithKline is paying the Harvard Stem Cell Institute $25 million in a five-year partnership that is aimed at developing new medicines for heart disease, cancer, diabetes, musculoskeletal diseases and other areas, with the work to be done at Harvard and several affiliated hospitals.
Pfizer is trying a slightly more independent variation. It has leased space for brand-new research labs in San Francisco and New York, staffed half with its own employees and half with postdoctoral students from local universities, including the University of California, San Francisco; Columbia University; Mount Sinai School of Medicine; Albert Einstein College of Medicine; and Weill Cornell Medical College. The goal, says Anthony Coyle, chief scientific officer of the project, known as the Centers for Therapeutic Innovation, is for the Pfizer and university scientists using the most advanced biologic technology and “working side by side on the same bench,” to find approximately eight promising compounds per lab that are good enough to get through early-stage human trials within two years. At that point, Pfizer would take sole control of the compounds. Since setting up the San Francisco lab in October, the collaboration has already identified eight potential drugs for treatment areas, including oncology, immunology and heart disease, according to Coyle. A third lab is expected this summer.
Neither Roche nor Pfizer would reveal how much money they’re investing, but other observers note that by piggybacking onto existing university facilities and staff, companies can save on overhead, new construction, supplies and salaries. For instance, Garaud says, several Roche projects use advanced-imaging facilities that were already in place at three universities in the Netherlands.
In addition to the more advanced status of the research, other factors make these arrangements different from the companies’ previous academic schmoozing. First, they are more structured. Whereas Roche scientists in the past might have asked a university scientist a question here and there for specific experiments, the new arrangement involves “true collaboration at the inception,” Garaud says. And at Pfizer, Coyle points out, “the individuals that partner with us will get complete access to Pfizer’s technology,” including proprietary antibody libraries.
Even without such formal programs, drug companies are increasingly setting up labs right next to universities so they can attend seminars, arrange private tutorials or at least breathe the rarefied air of Cambridge, Massachusetts, and Palo Alto, California. For instance, Novartis moved its R&D lock, stock and petri dish from its headquarters in Basel to a building that shares an atrium with a branch of the Massachusetts Institute of Technology. Similarly, Pfizer recently transferred a slew of researchers from Groton, Connecticut, to Cambridge. Merck built a 12-story research lab in Boston in a medical complex with Harvard Medical School, Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute and other top-name medical institutions.
Other major locales for this cross-fertilization include Washington University in St. Louis; Oxford University and the Wellcome Trust Sanger Institute in the U.K.; and Beijing’s BGI, a genome sequencing research center.
Alternatively, companies are bringing academia to them. While drug manufacturers have always hired freshly minted MDs and Ph.D.s, “now they’re getting experienced scientists with 15 years at academia,” even department chairs or holders of prestigious endowed professorships, says Barclays’ Butler. At Roche, Garaud says, “I’ve asked our HR team to ensure that our search profiles include the academic community.”
Among the academic stars cited: Michael Rosenblatt, Merck’s chief medical officer, formerly dean of ?Tufts University School of Medicine; Michael Ehlers, chief scientific officer for neuroscience research at Pfizer, formerly the George Barth Geller professor of neurobiology at Duke University; ?Anirvan Ghosh, about to become head of Roche’s central nervous system research, previously chairman of neurobiology at the University of California, San Diego’s biological sciences division; and Mark Fishman, a former professor at Harvard Medical School and chief of cardiology at Massachusetts General Hospital, who runs the Novartis Institutes of Biomedical Research lab in Cambridge. Except for Fishman, all were hired within the past year and a half.
Research is also coming from nonacademic sources. The Obama administration is creating a $1 billion center at the NIH, to be called the National Center for Advancing Translational Sciences and scheduled to launch in October, to jump-start drug development. According to the NIH web site, the new center would “seek ways to leverage science to bring new ideas and materials to the attention of industry.” ?That could range from screening molecules all the way to human tests, until the private sector finally steps in. Separately, philanthropies like the Bill & Melinda Gates Foundation have been funding research and manufacturing in areas without the profit potential to attract industry, such as AIDS and malaria in Africa.
In another major shift, groups of big companies are working together on research. ?Through the Alzheimer’s Disease Neuroimaging Initiative, 22 drug manufacturers, the NIH and two foundations have jointly invested $67 million in long-term studies looking for biomarkers that might characterize progressive stages of the disease. Data from the 1,000-person study, which is being run by the National Institute on Aging, are openly available online to researchers. A different kind of collaboration is Enlight Biosciences, a private company established in Boston in 2008 by PureTech Ventures (a venture capital firm) plus several academics and six Big Pharmas: Abbott Laboratories, Johnson & Johnson, Lilly, Merck, Novartis and Pfizer. Enlight will invest about $40 million in drug development technology, with the member companies getting access to any results.
Again, this is a sharp variation from traditional collaborations such as the cholesterol drugs Vytorin and Zetia, codeveloped by Merck and then-independent Schering-Plough a decade ago. Those have generally been one-shot deals to create or market specific drugs, involving two companies that each bring a particular expertise to the table. By contrast, the new endeavors are not aimed at one specific drug and this sentence doesn’t track, how should read? mean “new endeavors are not aimed at one specific drug and include many companies, some of which will share their results?include many companies, some of which will share the results.
The upshot of all this outreach can be seen in the companies’ budgets. According to Cooper of Deloitte, Big Pharma has gone from allocating 80 percent of its R&D money internally five years ago to just 50 to 60 percent today. The change, says Pfizer’s Coyle, “is very challenging because most pharmaceuticals companies are centralized and vertically integrated.”
Dramatic as those moves are, they are only the beginning. As the disease targets, government regulations and payment systems become more complex, industry observers say that companies are looking to outsiders for entire areas of expertise beyond research.
Viren Mehta, founder of Mehta Partners, breaks down the industry into four basic skill sets: research, development, manufacturing and marketing. As he sees it, there’s no reason a single company should expect to master all four or even two or three of them. “In the future there will be no big or small companies, no distinction between pharma and biotech,” he predicts.
The trend actually began in the 1980s with contract research organizations like Quintiles and Parexel — consulting firms that can conduct clinical trials or help companies maneuver the regulatory process. The earliest CROs, however, were limited mainly to statistical analysis and animal trials. Early last decade, Wyeth and Lilly each took a giant leap in outsourcing. As part of a total revamping of its research structure, Wyeth hired Accenture in 2001 to scan and “clean” the data from its clinical trials, returning the information to Wyeth for medical analysis, Robert Ruffolo Jr., who was then Wyeth’s senior vice president of R&D, said in 2005. In 2002, Lilly created an autonomous unit called Chorus Group specifically to outsource early testing.
Those actions remained outliers until recently. But in the past few years, companies have been dumping all sorts of responsibilities en masse. Bristol-Myers Squibb in late 2007 hired Accenture to handle much of its pharmacovigilance, or safety monitoring after a drug is on the market. In 2009, Merck sold off its Seattle-based gene expression lab (which does early-stage genetic analysis) to Covance, a big New Jersey–based CRO that was founded in 1997. Sanofi followed a year later, selling two research sites to Covance. And just this March, Lilly announced that it was outsourcing all bioanalysis of potential compounds — the analysis of how a molecule is absorbed and metabolized in experimental models, before human trials — to Advion BioSciences, a CRO with facilities in upstate New York and Indiana.
Genomics makes outsourcing even more feasible. Because drugs can be targeted to people with a particular genetic mutation, they can be tested in just those narrow populations rather than requiring traditional trials with thousands of subjects. That means the vast resources of large manufacturers may not be necessary to run the standard three series of human trials.
The castoffs won’t stop with R&D. Small companies already go outside for marketing, either by allying with Big Pharma or by hiring contract sales organizations similar to their research cousins. Pfrang of Deloitte says the big manufacturers too will turn to CSOs to supplement and support their in-house staff. This marketing help will be needed because “large pharma companies are redefining who their customers are, beyond just the prescribing physician,” says Pfrang’s colleague Orlan Boston, head of Deloitte’s M&A human capital practice in the Northeast. Today these decisions are also influenced by insurance companies, academic opinion leaders, patient advocacy organizations, pharmacies and companies that make the medical software that hospitals and doctors use to decide which drugs will be allowed in their formularies. Mehta predicts that patient groups, insurance companies and employers will play a larger role in drug development — in large part because companies won’t pursue third and fourth me-too drugs for which they won’t be reimbursed.
In addition, Tufts’s Kaitin sees CROs doing more regulatory submissions. If so, the FDA’s Woodcock says the source of the application wouldn’t affect the regulatory process. “Whoever wants to send something in, we’ll look at it,” she promises.
But if drug companies are parceling out all this work right and left, no one is sure what will remain. “If you sit down with a company and say, ‘What is the core competency of your company,’?” Kaitin sighs, “you’ll get an argument among their senior officials.” Indeed, experts offer a range of answers, from conducting clinical trials to global marketing to ultimate legal responsibility for safety. Inevitably, some will shrink, focusing on one or two specialties.
Still, a few common themes seem to emerge. Research is no longer a core competency. Different companies will have different areas of strength. Some may become little more than general contractors that gather the work of their subcontractors to submit to the FDA. Some may survive only as a brand name behind a distribution machine.
Countering that shrinkage to some degree is a trend toward expansion into nontraditional but related categories, as a hedge. One such area is emerging markets, where the populations can finally afford expensive brand-name drugs. IMAP, an organization of global M&A advisory firms, says that big Western drug and biotech manufacturers are targeting Argentina, Brazil, China, Egypt, India, Indonesia, Mexico, Pakistan, Poland, Romania, Russia, South Africa, Thailand, Turkey, Ukraine, Venezuela and Vietnam, whose combined pharma sales, IMAP predicts, will grow 15 to 17 percent this year, up from about $367.5 billion in 2010. Abbott, for one, acquired Indian generics maker Piramal Healthcare for $3.72 billion last May, and Sanofi paid $662 million for Medley, the third-largest drug company in Brazil.
Experts like Deloitte’s Pfrang and Hay’s Wilcox also see Big Pharma branching out more and more into nonprescription health areas, such as diagnostic tests, generics, animal medications and over-the-counter treatments. A strong line of consumer brands like ChapStick, Advil and Dimetapp was considered one of the advantages that Wyeth brought to its merger with Pfizer. And Novartis includes eye care, generics and consumer health (meaning nonprescription and animal drugs) among its five “pillars,” along with pharma and a joint category of vaccines and diagnostics.
However, it’s not clear how strong that expansion trend may be. Pfizer CEO Ian Read has said he is reviewing all nonpharma areas, and in April the company sold off a capsule manufacturing unit to Kohlberg Kravis Roberts & Co. for $2.38 billion. The unit had generated $750 million of Pfizer’s $67.8 billion in sales last year. GlaxoSmithKline said it will shed a cluster of over-the-counter brands with a total $813 million in sales. “There’s a question whether some companies have diversified too much,” says Deloitte’s Cooper. She suggests that the most successful companies will expand only into narrowly targeted areas with a direct relationship to their pharma expertise, like diagnostic tests linked to personalized medicine and devices that also incorporate drugs. Meanwhile, China illustrated some of the risks of emerging markets when it announced this spring that it was ordering drug price cuts.
All these predictions of shrinking, outsourcing and rethinking the industry model lead to the obvious parlor game of guessing which names will survive as full-fledged, real companies.
Roche and Novartis seem to get the most votes. Barclays’ Butler cites Novartis’s cutting-edge lab in Massachusetts, while Ira Loss, executive vice president of research firm Washington Analysis, which specializes in pharmaceuticals, praises that company’s “widely diversified product line.” Roche, of course, benefits from its ownership of Genentech, one of the oldest, biggest and most successful biotechs, with blockbusters like Avastin and Herceptin for cancer. As for returns, Novartis was in a virtual tie for the industry’s best stock performance over the past decade, and Roche was in the top half, according to M.P. Advisors, the Indian arm of Mehta Partners, which provides the firm’s statistical analysis. For the short term, based on this year’s first-quarter results, Merck was a surprise winner, with profits nearly tripling on a slight increase in sales and deep cost-cutting, and its stock rose 28 cents. Novartis also beat sales and profit expectations.
The secret of success in pharma, says Boston Consulting’s Tollman, is the same as for any industry: “To have a valid strategy and be well run and disciplined.”
Although T. Rowe Price’s Jenner isn’t naming names, he sees a shakeout within the next three years, with only those companies that have strong late-stage pipelines remaining full-size.
Not all observers believe that the basic industry model will change so drastically. Some think that any increase in outsourcing will be limited to early-stage research arrangements with universities, somewhere between the old-style theoretical research and midstage human trials, mainly because that’s where Big Pharma is weakest. These skeptics argue that there’s no point seeking outside cooperation beyond basic research, because industry is better than any potential partners at all the other functions it’s been doing for years. The goals for a drug company official, Tufts’s Kaitin says, are FDA approval, a promotion–– and a bonus. By contrast, he adds, an academic scientist seeks “a government grant to continue your research and publication.”
With its new labs, Pfizer has to balance its need for trade secrets with its partners’ expectation of academic freedom, Coyle acknowledges. Add to those problems the ivory tower’s historic disdain for commerce, which has only been amplified by recent scandals in which drug companies have paid professors to write — or even worse, merely add their names to — articles in medical journals praising those same companies’ products. But those hurdles must be overcome. Big Pharma can no longer cruise happily into the future on weak and expensive research, limping mergers and a conceit that all new products must be invented internally.