Fiction: Cromwell’s England to Galactic Intrigue

BioWorld staff writer Sharon Kingman suggested the “cracking novel” Sacred Hunger, by Barry Unsworth, that features an underlying science theme on the discovery of the circulation of the blood. She also recommended Booker Prize winner Bring Up the Bodies, Hilary Mantel’s sequel to Wolf Hall, a title from last year’s reading list.

Barbara Fox, CEO of Avaxia Biologics Inc., looks forward to reading And the Mountains Echoed by Khaled Hosseini. “If this matches his earlier books, it promises to provide both a great read and a window onto the moral complexities of our multicultural world,” she said.

BioWorld’s Randy Osborne recommended two titles in the fiction category, describing All That Is, by James Salter, as “a novel by the master, still going strong.” Salter, author of nearly two dozen books, turned 88 earlier this month. His newest tome follows a soldier looking for love after World War II. The book is “full of fine, Salterian lines such as, ‘He was her older brother, three years older, and had the handsome face of someone who has never done much,’” Osborne recounted. On the other hand, A Guide to Being Born: Stories, by Ramona Ausubel, includes “gem-like, poetic, image-filled short stories that cycle through all the stages of life,” Osborne said.

“What would summer be without another installment of the Stephanie Plum series by Janet Evanovich?” asked Mary Sylvia, intellectual property attorney at Baker & Hostetler LLP. This summer’s release, Notorious Nineteen, features Stephanie’s Grandma Mazur going undercover in an assisted living facility. “These books are fast, funny, well-written reads – just right for summer vacation,” Sylvia added.

Former biotech marketing and communications manager Katharine Russell suggested her mystery set in the San Francisco Bay area’s biotech community – a setting she knows well from many years heading the Russell-Welsh Inc. public relations agency in San Mateo. A Pointed Death, published in 2010, follows the exploits of biotech consultant Nola Billingsley as she discovers that one of her clients is stealing proprietary information from other start-ups. As Russell deliciously describes, the plot unfolds “in a town everyone loves but secretly believes is in need of its own 12-step program.”

And BioWorld’s Catherine Shaffer, an award-winning author of science fiction and fantasy short stories, recommended Redshirts, by John Scalzi. “It’s a fun, fast read featuring those lovable, disposable characters from a universe much like Star Trek,” she said.

Genomics, Cloning and the Stuff of Science

Given recent news about the cloning of human embryonic stem cells, BioWorld’s science editor Anette Breindl suggested two related novels: The House of the Scorpion by Nancy Farmer – a National Book Award Winner for Young People’s Literature that her son is reading now – and Never Let Me Go by Kazuo Ishiguro.

Leslie Williams, president and CEO of ImmusanT, plans to read Thinking Fast and Slow by Nobel Prize winner Daniel Kahneman. Williams also recommended The Scientist as Rebel by Freeman Dyson, whom she described as “an eloquent writer.” The book describes scientists “as free spirits who resist cultural restrictions,” she added. “The exploration of minds of great scientists of the past is incredibly fascinating, both philosophically and practically.”

BioWorld staff writer Cormac Sheridan described Misha Angrist’s Here Is a Human Being: At the Dawn of Personal Genomics as “one of the best science books I’ve ever read.” Angrist was among the first to sign up for George Church’s Personal Genome Project, he pointed out, so the book “combines an authoritative, insider account of the perils of having your genome investigated, with a deeply felt consideration of the issues at stake.”

Also on Sheridan’s reading list is Jim Al-Khalili’s Pathfinders: The Golden Age of Arabic Science, “which promises to be a journey of complete discovery, as Al-Khalili, an Iraqi-born, UK-based physicist, charts 700 years of scientific exploration across the Arab world,” he explained. “It’s a call for a much wider, more inclusive understanding of the origins of scientific thought.”

On a practical note, Lawrence Helson, CEO and president of Sign Path Pharma Inc., plans to review Lung Cancer Therapy Annual 7, edited by Rolf A. Stohel, “because we are initiating a lung cancer trial, and it’s a good review,” he said.

Around the World of Nonfiction

The former chief operating officer at the Burnham Institute for Medical Research, Karin Eastham still sits on the boards at Geron Corp., MorphoSys AG and Trius Therapeutics Inc. – among others – and has a social network that numbers dozens of biotech insiders. She also has a culinary hit on her hands with Cook the Part, a cookbook she designed not only for people who love to cook – and eat – but also as a teambuilding guide. Although Eastham’s party guests have included chemists, venture capitalists and CEOs, the book is designed to help even novice hosts to create memorable meals.

Another juicy bit of writing was recommended by one of @BioWorld’s tweeps, but this volume has nothing to do with food. Backstage Wall Street: An Insider’s Guide to Knowing Who to Trust, Who to Run From, and How to Maximize Your Investments was penned by financial advisor Joshua Brown, author of The Reformed Broker blog and better known to his 47,000+ Twitter followers as @ReformedBroker. Given that the biotech world is no stranger to the vagaries of Wall Street, this “brutally honest look at the investment business,” published last year, set tongues wagging.

John McManus, president and CEO of Aeolus Pharmaceuticals Inc., suggested delving into Religious Freedom: Jefferson’s Legacy, America’s Creed by John Ragosta. “I have read a great deal by and about Thomas Jefferson and saw this book when I visited Monticello,” he said. “I found the book interesting given current efforts to curb religious liberty in our country and the fact that Jefferson’s views on this issue are often misinterpreted.”

The other title on McManus’s summer reading list is Ten Universal Principles by Robert J. Spitzer, a former president of Gonzaga University and physicist. “I have heard him speak on astrophysics, morality and spirituality and look forward to his insights on the key principles one should consider in life,” McManus said.

Greg Brown, founding managing director of HealthCare Royalty Partners, plans to read Stradivari’s Genius: Five Violins, One Cello, and Three Centuries of Enduring Perfection. Author Toby Faber, scion of the eponymous book imprint that published T.S. Eliot, Ezra Pound and other giants of early 20th Century British literature, traces the history of five violins and one cello from the master luthier, Brown pointed out. “Stradivari mixed science (acoustics), art and business in a manner that has never been replicated – an accomplishment that seems an apt metaphor for the world of biotechnology,” he said.

A title from Cormac Sheridan’s “wish list” is Secrets of the Irish Landscape, edited by Matthew Jebb and Colm Crowley, which he described as a “history of the Irish landscape and of the development of earth science in Ireland, from the pioneering field studies of Robert Lloyd Praeger more than 100 years ago to recent discoveries demonstrating the distinct characteristics of Ireland’s flora and fauna.”

Another on Osborne’s list is Legs Get Led Astray, featuring personal essays by “fearless and funny” new writer Chloe Caldwell. In a similarly introspective vein, ImmusanT’s Williams suggested David Whyte’s seventh volume of poetry, Pilgrim, which she called “an incredible collection. I had the opportunity to hear David present at a CEO retreat and immediately purchased the book. It’s thought-provoking.”

Speaking of poetry, BioWorld’s executive editor, Lynn Yoffee, said she was so moved by Richard Blanco’s One Today: A Poem for Barack Obama’s Presidential Inauguration that she immediately dug into and recently re-read (because it’s that good) Blanco’s Looking for The Gulf Motel, a moving collection of poetry by an artist who was the youngest, first Latino and first openly gay person to serve as an inaugural poet.

Mari Serebrov, BioWorld’s Washington editor, is beginning research on her next book (read on for a description of her first novel), which includes academic texts on colonialism in Africa. On a lighter note “but on the same subject and at the top of the list is Donato Ndongo’s Shadows of Your Black Memory,” she said. Written in the creative vein of Spanish authors generally associated with Latin America, Shadows revolves around a young man’s reflections on his childhood in the final years of Spanish rule in Africa’s Equatorial Guinea. “I’m reading it for enjoyment, as well as for writing style and content,” Serebrov added.

Biographies: The 1^st Century to Post-World War II

Greg Brown also is preparing to dig into The Last Lion: Winston Spencer Churchill: Defender of the Realm, 1940-1965, the third volume of William Manchester’s biography of the British statesman. “Manchester is an eminently readable historian, whose first two volumes were masterful syntheses of biography and social, political and military history,” Brown said. “The third volume, begun when Manchester was in failing health and completed posthumously by his collaborator Paul Reid, promises to be an engaging ride from the onset of the second World War through the post-war period.”

Don Johnston, senior vice president and group publisher of BioWorld’s parent company, AHC Media, recommended Yokohama Yankee, penned by Leslie Helm, a friend from graduate school at Columbia University. A business journalist and editor in Seattle, Helm traces his family’s long history in Japan and considers the impact his American and Japanese roots have had on his identity. “As the world shrinks, I am fascinated by stories about the interactions between or among cultures,” Johnston said, describing the book as “terrific.”

A true classicist, PhenoMatriX Inc. CEO Kosta Steliou plans “to continue reading about people in antiquity whose impact is still felt in our world today” by finishing The Complete Collection of Plutarch’s Parallel Lives by 1^st Century Greek historian and biographer Plutarch.

And Sharon Kingman suggested Claire Tomalin’s biography, Samuel Pepys: The Unequalled Self, which recounts, among the famous diarist’s other tidbits, “a fascinating account of the surgery he had for a bladder stone…in 1600 and something!”

Personal, Professional and Business Development

SciFluor CEO Arthur Hiller suggested The Heart and the Fist: The Education of a Humanitarian, the Making of a Navy SEAL by Eric Greitens. “The author joined the Navy SEALs with the idea that the heart and the fist, together, are stronger than either one alone,” he explained. “The same applies more broadly to life and to management. Empathy is an important component of leadership, and the ability to balance strength and emotion is critical to leading organizations.”

Hiller also is reading Work Like a Spy: Business Tips from a former CIA Officer, by J.C. Carleson, which examines tactics used by CIA officers to recruit informers and agents and applies those techniques to recruiting priorities in private-sector businesses. The book includes “analogies and examples that ring true and represent interesting strategies to tuck away for use as part of the recruiting and interviewing processes we use within our respective organizations on a daily basis,” he said.

Barbara Fox is planning to re-read Good to Great: Why Some Companies Make the Leap… and Others Don’t by Jim Collins. “As our company grows, the lessons of how to build a great company are more relevant than ever,” she said.

ImmusanT’s Williams recommended Lean In – Women, Work and The Will to Lead, the much-discussed book by Facebook’s Sheryl Sandberg, which she called “inspiring.”

And Bill Garner, CEO of Invion Ltd. (formerly Inverseon Inc.) mentioned his new book, Garnering Capital, in which he shares lessons learned on how researchers, inventors, entrepreneurs and investors can navigate the often treacherous road to success in the life sciences.

Finally, a Classic in the Making…

BioWorld’s summer reading list would be incomplete without showcasing Mari Serebrov’s standout historical novel, Mama Namibia. The fascinating and heartbreaking narrative, based on a true story, recounts the suffering and perseverance of a young girl, her family and the people of what was known as South West Africa during a 1904 genocide that proved to be the training grounds for the Holocaust. The book, by turns joyous and tragic, was selected by Genocide Watch as the only novel on its resource list.

Serebrov recently was honored by the Specialized Information Publishers Association for her outstanding work on BioWorld’s comprehensive report, The Biosimilars Game: A Scorecard for Opportunities, Threats and Critical Strategies. Her first novel is already attracting similar praise. As BioWorld’s Yoffee, pointed out, “Those of us familiar with her journalistic endeavors know Mari is a stickler for detail. That, of course, is apparent in her book. But Mari’s creative side also shines. Mama Namibia is a heartwarming but wrenching story that follows the life of a girl who survived the horrors of genocide. It was a real eye-opener for me.”

Goldacre, it turns out, is as much bothered by the secrecy of data as by its quality, and he has also set up an activist website, where the public can petition for “all [clinical] trials to be registered, for all summary results to be reported, and for full clinical study reports [CSRs] to be made publicly available,” he writes on his original site, which takes its name from Goldacre’s previous book. “CSRs are important, because it is now clear that brief summaries about trials [such as academic journal articles] can be incomplete or misleading,” writes Goldacre.

I probably took so long to get through the book because I sensed that the heft text would take on “the usual Big Pharma critiques, touching on the ethical morass of human trials and the infuriating dirty tricks pharmaceutical firms use to market their drugs both to patients and to doctors,” as a review in the New York Times pointed out late last month. But there’s more to the book.

Among the firms Goldacre, a London doctor, takes to task is GlaxoSmithKline plc, which surprised the author and probably everyone else in February when the firm came aboard his cause, and agreed to post its CSRs online. “They have also made sensible noises about the practicalities, which shows that they have thought about the implications, and they also discuss prioritizing which CSRs to work on first,” writes Goldacre. (Another reason for my slow going with this book: dread of stiff British, physician-style writing and clichés. Practicalities, implications and prioritizing. “Because [GSK has] discussed these technical details – while I will always wait for the proof in the pudding – I do not believe this is mere lip service,” he goes on, wedging in a couple more.)

But, as a blunt instrument, the book seems to be having an effect. Will AstraZeneca plc join GSK? Goldacre summarily smacks down the developer of Iressa (gefitinib), a rather easy target, in his book. “Large, well-conducted fair tests of Iressa had shown that it was no better than a dummy sugar pill containing no medicine,” he writes, yet patients who turned out at an FDA advisory panel meeting sang the drug’s praises.

“When the committee charged with approving the drug [sic] cast their votes, they went 11-3 in favor,” Goldacre recalls. “We can only wonder if individuals who had not been successfully treated with Iressa would have been flown across the country to speak their personal truth. Perhaps not. Perhaps they might be dead.” Perhaps. But the issue of full trial-data disclosure, thanks to Goldacre’s book, is anything but.

The public hearing speakers, along with the usually silent patient member of the panel, seem to have one function – to let the FDA check off the box for patient involvement. But patients with orphan diseases and their families deserve more than token involvement.

After all, those patients voluntarily took what could be life-threatening risks to participate in a clinical trial. And even though a sponsor may be paying for their travel to be at the hearing, the patients and their families are freely giving their time in the hope that their voices will be heard and weighed by the members of the adcom and the FDA staff, all of whom are paid to sit through the meeting.

So why do they bother to speak up? The patients are there because they want to have a say in what clinical trial endpoints really matter and what risks are acceptable. They want their first-hand experience with a disease and potential treatments to make a difference for others who may face the same challenges in the future. And they want to ensure that the doctors who are on the front lines of treating the diseases are being heard in the regulatory process.

Instead, the patients are greeted with polite smiles and their words are dismissed as soon as they’re spoken. And the doctors are disregarded as “conflicted” because they participated in the trials. “It was so disheartening,” Dena Battle said of her first experience of testifying before an adcom. “We were sort of dismissed as just emotional anecdotes.”

Both Dena and her husband, Chris Battle, who is fighting kidney cancer, spoke in favor of approval of AVEO Oncology Inc.’s tivozanib as a treatment for renal cell cancer. Unswayed by the patients’ experience, the advisory committee spent the rest of the session scolding AVEO for its trial design.

While some mistakes may have been made with the trial, Dena said the meeting would have been much more productive had the committee – comprised of biostatisticians, breast cancer specialists, hematologists, a pediatric oncologist and a prostate cancer specialist – engaged in a thoughtful discussion with the renal specialists in the room about how AVEO should proceed with the RCC indication. Instead, “the doctors that know most about this disease . . . were all shut down,” Dena told BioWorld.

As a result, the only vote in support of the drug came from patient representative Dan Lumley. Now AVEO is facing shareholder lawsuits, and its partner Astellas Pharma Inc. has pulled out of the RCC development of the drug. While tivozanib is still being developed for breast cancer, it’s unlikely the drug will be developed for RCC, even though it showed promise in the orphan disease.

Over the next few years, the FDA is likely to devote considerable time and resources in figuring out how to implement the FDA Safety and Innovation Act provisions requiring patient involvement in the drug approval process. The first step is a no brainer: Actually listen to the patients who are trying to live with the disease. Step 2: Consult with the doctors who are the specialists in dealing with the orphan disease.

Frankly, I’m satisfied he’s going to serve time. Angry that our judicial system can’t penalize him with a longer sentence given the repeated widespread impact his actions have had on our industry. Amazed at his gall to repeat his offenses. Unforgiving that he blames his bipolar disorder for his misdeeds.

Blech’s troubles began in September 1994 when his investment boutique, D. Blech & Co., suffered a liquidity crisis as capital reserves dipped below federally regulated levels and ceased trading activities on Nasdaq. The news sent the stock prices of numerous Blech-financed biotech start-ups spiraling down in an already bear market. His company’s portfolio of 11 biotech firms lost more than $168 million in market capitalization in one day.

Blech, who founded his investment firm in 1990, was touted as the financial “white knight” of biotech start-ups. Four years later when his empire crumbled, some of his brokers not only received rubber paychecks, but they also were left without even the most basic tools of the trade, including telephones. It was really sad.

His former brokers said he ran “a sleazy boiler room operation,” pressuring them to get clients to buy newly issued shares in companies underwritten by Blech and urged them just as strongly to advise those clients not to sell if the price started rising.

As the years stretched on, it only got messier.

A Florida attorney for former D. Blech & Co. employees was sentenced to five months in prison for obstructing an SEC investigation in 1997. Lloyd Schwed, of Jupiter, Fla., pleaded guilty in November 1996 to withholding and agreeing to destroy tapes subpoenaed by the SEC. Schwed represented the 10 former brokers in complaints filed against Blech. The brokers were ultimately awarded hundreds of thousands of dollars in damages stemming from the collapse of Blech’s business.

In 1997 he was charged with scheming to defraud Bear Sterns & Co., which provided clearing services for securities transactions made by Blech’s brokerage firm. But the judge felt sorry for him and refused to accept a guilty plea when he learned Blech was on meds for manic-depression.

Too bad. Because he turned right around and did it again. Blech made major stock purchases in three companies in 1997 ‑ Gene-Medicine Inc., Escalon Medical Corp. and Homecom Communications Inc ‑ without having enough assets to pay for them.

Who would stop this guy? U.S. District Judge Colleen McMahon slammed the gavel down this week.

The Associated Press reported that McMahon repeatedly scolded Blech during sentencing, which includes four years plus $1.3 million forfeiture. She called him a “serial stock manipulator” because he committed the same crime four times even after being granted leniency when he swore he wouldn’t commit another crime. Hooray for a strong judge.

So, almost two decades since the troublemaking started, I say good riddance, David Blech.

The invasion of the multidrug-resistant superbugs is not a nightmare in the making. It’s already here. And it could be years before a new superhero lands in Metropolis to knock out the worst of the worst of these villains that are set on world domination.

In a twist on the usual comic book tale, the super-resistant strains of CRE, malaria and tuberculosis threatening the world today are not the work of a mad scientist scheming away in a remote underground lab. They are a force of nature – helped along by our over-reliance on cheap, decades-old anti-infectives.

But scientists could hold the answer to stopping the bad guys in their tracks. “All” they need to do is identify a superhero, or discover a form of kryptonite, to strip the nasty bugs of their power. The trouble is that many of the scientists who know these bugs, and the big pharma firms the scientists work for, are ignoring the problem.

That wasn’t always the case. In years gone by, big pharma was on the frontlines of the pathogen battle. Then the generics took over the fight, and the cost and time involved in developing new drugs soared. As a result, big pharma retreated – to a hero-for-hire industry that’s focused on blockbuster drugs that can command high prices, multiple indications and long-term use.

Unfortunately, the heroes that chase down superbugs, especially those terrorizing developing countries, don’t fit that costume. They have to be affordable. And their use has to be limited, so there can be no indiscriminate prescribing, off-label promotion or expanded indications. Otherwise, the bugs will learn the secrets of their powers and devise a way around them.

When big pharma scientists redirected their X-ray vision to blockbuster drugs, they created a brain drain in the R&D necessary to identify a new breed of superheroes to take on drug-resistant bugs. Some of the missing-in-action scientists were the ones who had discovered useful molecules and figured out how the bugs evolve their super resistance. When they fled Metropolis, they took that knowledge with them.

It will take many, many years to overcome the brain drain, Helen Boucher, director of the Infectious Diseases Fellowship Program at Tufts Medical Center, told BioWorld. “If we ever can,” she added.

Meanwhile, as biotech startups scramble to find the money and race against the clock to fill in the knowledge gaps to develop a new brand of hero that might appear on the scene in another decade or so, the world continues to face emerging strains of virile superbugs that make yesterday’s superhero anti-infectives look like impotent has-beens.

Partnering, networking and making new friends are all top-of-the-agenda for the biopharma industry’s largest U.S. gathering. As you’re preparing to join 16,500+ of your colleagues at the 2013 BIO International Convention in Chicago, we’d like to introduce you to a few standouts featured in the stories below. Also, come meet the BioWorld people, who are pretty interesting, too, at booth 1573. Plus, you can collect BioWorld’s giveaway, which is both practical and sentimental. For 15 years, Publisher Donald R. Johnston has masterminded the creation of our lids. It’s a hotly sought after gift, so come early before we run out.

Avalon’s Lichter: ‘Laid-Back’ Savvy Keeps Deal Flow Strong

When it comes to getting venture capital deals done, the science and the financial terms naturally take center stage, but the personalities of the players need to mesh, too, for the best outcomes.

Women Leaders in Biotech: ‘Walls Are Coming Down’

The glass ceiling is shattered, and barriers to women’s participation in the biotech industry have fallen at every level, including the highest. That is the happy testimony of four leading women in biotech slated to present at BIO 2013, including Rachel King, co-founder of GlycoMimetics Inc.; Leslie Williams, president and CEO of ImmusanT Inc., Jessica Flechtner, vice president of research at Genocea Biosciences Inc.; and Denise Pollard-Knight, managing partner with Phase4 Ventures.

CEOs of Newly Public Biotechs Balance Work and . . . More Work

The initial public offering window may be creaking open for biotech – thanks in part to the new emerging growth company designation included in last year’s JOBS Act – but running a publicly listed small biotech requires as much dedication as ever. Among speakers at BIO 2013 are two CEOs who can attest to that, having helmed their respective companies through the process in the past year – Dave Pritchard of KaloBios Pharmaceuticals Inc. and Lonnie Moulder of Tesaro Inc.

Unconventional Paths Give Young Standouts a Step Up

Among the thousands of interesting people who will be attending the 2013 BIO International Convention in Chicago are young standouts who are already making their mark in biotech, including Josh Sommer, Isaac Kinde, Laura Deming and Andina Mangubat

Navigating Successful Biotechs: CEOs Need to be Visionaries

It takes a special kind of person to be able to help navigate a biotechnology company from its early stages, with all its attendant hopes and dreams into the reality of a truly therapeutic product organization, which generates revenue and builds value for its shareholders. The job description calls for visionaries with business savvy and the ability to keep a positive attitude even when bumps in the road are encountered. BioWorld Today caught up with two such visionaries: Kleanthis Xanthopoulos, president and CEO of Regulus Therapeutics Inc., and Ingmar Hoerr, CEO of CureVac GmbH.

Mukherjee regaled the audience with an apocryphal tale of a historian who was asked to predict the future of the Soviet Union and answered that “in the Soviet Union, the future is quite easy to predict. The problem is the past. The past keeps changing.”

That problem, he said, is also one in cancer research – faced with a cancer cell, we have ever-changing notions of how it got to be that way. Mukherjee traced the dominant theory of cancer’s natural history from the 1860s, when Rudolf Virchow first argued that dysregulated cell division is the root cause of cancer, to the notion now taking root that cancer is an organismal disease that involves changes to the microenvironment and the immune system of the cancer patient as well as to the genes and genomes that make up the cancerous cells.

Along the way, he shared fascinating stories of cancer and its treatments. The first chemotherapy was a chemical cousin of notorious World War I weapon mustard gas; pioneering surgeon and Johns Hopkins University co-founder William Halsted was addicted to both cocaine and morphine, which in his day was used to treat cocaine addiction; in the 1960s, philanthropist and medical research champion Mary Lasker thought that the cancer problem would be wrapped up by 1985.

At BioWorld, we’ve recommended The Emperor of all Maladies before, of course. It’s too much in our sweet spot not to. But good advice never gets old, and so if you have not read the book, it is still worth heading to your local bookstore, or library, and picking up a copy.

The Ingelwood, Calif.-based firm said it was changing its name to “AmaginAb,” because most of the successful firms in biotech have names that start with the letter ‘A” and “we were forced to acknowledge that we might never get acquired with a name that starts with ‘I’,” said CEO Christian Behrenbruch.

Plus, the new name better reflected its “overall awesomeness.”

But never fear. ImaginAb is really keeping its name, so don’t rush to update your Outlook contacts or rolodexes. The firm said it opted for this April Fools’ Day stunt because “we are hiring and wanted your attention.”

Well played, ImaginAb. Well played.

Of course, we realize that bad mutations can happen to good cells. The idea that most mutations are actually bad for an organism is a basic tenet of evolutionary theory. But then, the theory goes, the bad mutations get weeded out because their owners are now at a disadvantage.

By and large, of course, the reason we think of evolution like that is because it’s true. But every now and then, I come across papers that bring home the fact that evolution is also very complex, and not necessarily a one-way street toward the better.

Two such papers recently have made this point. One showed that evolution can let cells permanently acquire things that are bad for them – in this case, mutations that slow their growth. The other, while it does not deal directly with evolution, suggests that processes such as inflammation can evolve into different directions for reasons that remain mysterious to us.

The first paper, published a few weeks back, deals with so-called passenger mutations, and shows that instead of being neutral, they in fact put a drag on cancer cell growth.

In their work, the authors showed what senior author Leonid Mirny called a “counterintuitive” truth: that “in an evolutionary process, you can accumulate mutations that are bad for you.” That is exactly what happens to cancer cells, where driver mutations that give the cells a growth advantage can take passenger mutations that give them a disadvantage along for the ride.

The second paper does not deal directly with evolution at all. Instead, its authors showed that the inflammatory processes that happen in mice are very different from those that happen in humans.

You can find the details here and here. But basically, it appears that humans have a much stronger inflammatory response to bacteria.

Why? Because they evolved that way. Well, yeah, but why?

“The assumption is that there has to be some advantage to the way we do it,” co-first author Shaw Warren told BioWorld Today when his paper came out. “But the fact of the matter is that no one has been able to make a convincing case for what that advantage might be.”

If the sequester stayed in place, NIH Director Francis Collins said the agency would give “hundreds and hundreds” fewer grants than it would have awarded otherwise, slowing down important research. Speaking at a news conference, Collins said the NIH was trying to avoid employee furloughs, but he couldn’t promise they wouldn’t occur.

That’s when someone asked a question that others were likely thinking: “Doesn’t the NIH have any fat it can trim?”

“No,” was the reply, especially since the sequester was falling on the heels of several years of nearly flat budgets for the agency. Collins pointed out that because of those flat budgets, the NIH has lost about 20 percent of its spending power in recent years.

Collins painted a similarly bleak picture last year when he testified before a House subcommittee. Even without the sequester, researchers had only a 17 percent chance of getting NIH grant funding, one of the lowest rates in history, he told the Energy and Commerce’s Health Subcommittee. In years past, a researcher had a 30 percent chance at funding.

Today, the average age of a researcher getting a first grant is 43. That fact is enough to send young scientists into other careers, depleting the next generation of researchers and jeopardizing the nation’s status as a leader in medical R&D.

While the numbers are discouraging, there is something that would enable the NIH to fund more researchers and stretch its limited research dollars, even under sequestration. The solution? Limit the indirect costs universities can take from agency grants to cover facilities and administration (F&A).

While many foundations spend less than 25 percent of their grants on indirect costs, some universities are spending up to 95 percent on overhead, Rep. Tim Murphy (R-Pa.) said at the subcommittee hearing last year. Repeating a previous conversation with Collins, Murphy listed several private universities that charge excessive indirect costs on NIH grants but spend little of their own money on research. For instance, Harvard University, which has an endowment bigger than the NIH budget, applied 75 percent of its NIH funding to overhead costs and spent zero of its own funding, the congressman said.

Such practices aren’t limited to NIH grants, as the F&A rates for research grants are calculated in accordance with federal-wide guidelines issued by the Office of Management and Budget. “F&A cost rates are negotiated and established by the federal government to ensure that they are fair and equitable and that the federal government pays its fair share of these costs,” NIH told BioWorld recently.

Given current budget constraints and the fact that many universities are making money by licensing the intellectual property resulting from NIH-funded research, it may be time to rethink the government’s “fair share” of those F&A costs. Putting tighter caps on indirect costs would give the NIH more money to fund its core mission of research rather than subsidizing universities that will profit from that research.

Editor’s note: How much NIH grant money should go toward indirect costs such as facilities and administration? Cast your vote at bioworld.com. Look for our poll on the bottom, right side.