Also published on this date: Shelf Awareness for Wednesday, March 1, 2017

Wednesday, March 1, 2017: Maximum Shelf: Rigor Mortis: How Sloppy Science Creates Worthless Cures, Crushes Hope, and Wastes Billions

Basic Books: Rigor Mortis by Richard Harris

Basic Books: Rigor Mortis by Richard Harris

Basic Books: Rigor Mortis by Richard Harris

Basic Books: Rigor Mortis by Richard Harris

Rigor Mortis: How Sloppy Science Creates Worthless Cures, Crushes Hope, and Wastes Billions

by Richard F. Harris

Richard Harris, a science reporter for National Public Radio (NPR), presents a fascinating, thoroughly researched exploration of the advances, traps and pitfalls of biomedical science in Rigor Mortis: How Sloppy Science Creates Worthless Cures, Crushes Hope, and Wastes Billions.Harris pairs statistics, contemporary and historical facts, interviews and personal stories from influential scientists in academia and private labs with accounts of patients facing illnesses and the rigmarole of medical trials to add a human dimension to the scientific aspects. This all works together to shine a bright light on the limitations and politics of modern biomedical research, which largely boils down to problems with investments and pressures of time, professional reputation and money.

The book begins by extolling some of the astounding strides made in medicine. This includes the deciphering of the human genome, our genetic blueprint, and how it has afforded greater insights and technology for research labs, which can now readily access information relating to diagnoses, treatments and cures of illness and disease. Antibiotics, drugs designed for specific infirmities, vaccines and heart surgery have increased life expectancy while also deepening the pool of finances allotted to scientific research. Harris notes that "the average American household spends $900 a year to support biomedical studies." Some of that is money baked into the price of costly prescription drugs and medical treatments, as pursuing biomedical goals is expensive, and federal funding is actually shrinking.

The rate of new drug development and approval has been falling since the 1950s. Yet, each year, more than a million biomedical studies are published in scientific literature. Research, however, has proven that "many of them are simply wrong." It's this hypothesis that sets up Harris's well-constructed narrative that demonstrates how, when an "exciting scientific discovery is reported, scientists are often quick to jump on the bandwagon without considering whether the original finding is in fact true."

In 10 well-drawn chapters, Harris documents flaws in the medical research process and how it has "gone astray, as perverse incentives discourage scientists from following the rigorous path of top-quality science." The culture has become such that scientists are often forced to choose between doing what is right and what is necessary to keep their labs and their careers afloat.

The work of C. Glenn Begley emerges as a cornerstone of Harris's reporting. Begley, an Australian-born scientist, left academia after 25 years to work for Amgen, a Southern California cancer research biotech company. Begley and his staff set out to find hopeful preclinical research that might spark new cancer drugs. After combing through a trove of experiments and data that could lead to groundbreaking new medicines, Begley asked Amgen scientists to repeat documented experiments to ensure they would come up with the same results put forth in the literature. He soon discovered that most of the time, Amgen labs could not replicate those successes.

Every dead-end report was filed away by Begley. And before he left the company, he resurrected the most promising leads, selecting 53 papers. This time, he asked the scientists who first published the reports to provide more information. Amgen then set out to reproduce the data with that exact material. If they failed, Amgen went one step further, and sent its own scientists to labs to witness how the original experiments were executed. Alarmingly, only six labs--or one out of 10--could reproduce the results.

This sobering discovery was published by Begley and an associate in 2012. The report spelled out the problem in stark terms, indicating a reproducibility crisis in biomedicine and warning that widely cited work and preclinical data, often marred with errors, missteps and red herrings, was published anyway due to pressure on scientists who feared that funding might be pulled from long-term projects.

Begley expected the report to serve as a "shot across the bow" that would change biomedical culture and open a healthy discussion. Instead, it was met with fierce opposition and skepticism from within the biomedical community. The report itself--and the aftermath of bringing such glaring shortcomings public--sets the foundation for all that follows in Rigor Mortis. Harris utilizes Begley's findings as a launchpad to dissect the scope of faulty methods, dubious technology, perverse incentives and the reasons why scientists don't always dig deep enough to ensure that studies are actually true.

Harris offers detailed supporting data and examples surrounding problems in the areas of funding, grants, publication and fame. He expounds upon the politics and intellectual tug-of-wars of biomedical science in academia and in the pharmaceutical industry, along with the many problems inherent in scientific training, integrity and the challenge of practicing "precision medicine." He explains the role of the F.D.A., federal guidelines and data sharing, along with the ways in which the biomedical industry manages failure and misconduct, algorithms and statistics on the road to forming conclusions. Harris concludes by aiming his focus on the efforts of the scientific community to seriously weigh and consider Begley's report. He emphasizes a need to raise standards of biomedical practice to improve the reliability of clinical research and data.

Embedded throughout this scientific exposé are patient case studies. Harris paints clear portraits that demonstrate how biomedical science filters down to the ill and infirm and those who love them. The personal stories about people caught in healthcare quagmires and the defects of the clinical trial industry add an emotional subtext that fleshes out the well-presented scientific analysis. These case histories will hold appeal for readers who are scientists, as well as laypeople searching to better understand the far-reaching consequences of biomedicine and its effect on humanity.

The plethora of information Harris presents is well-supported and makes a strong case, emphasizing the flaws embedded in the culture of biomedicine and the lack of transparency in the industry. Harris states, "The overarching goal of biomedical research is to understand the basic processes that lead to disease so that medical science can intervene to ease human suffering and improve health." Reading Rigor Mortis will help the biomedical community--and those affected by biomedical science--assess the state of the industry and make much-needed improvements that can benefit all. --Kathleen Gerard

Basic Books, $28, hardcover, 272p., 9780465097906, April 4, 2017

Basic Books: Rigor Mortis by Richard Harris

Richard Harris: The Lack of Rigor in Biomedical Research

 photo: Meredith Rizzo

Richard Harris has served as a science journalist with National Public Radio (NPR) for the past 30 years. He's covered a wide range of topics from medicine to the environment, and he's traveled to all seven continents. His favorite places include the South Pole and Greenland. "Ice is simply beautiful," he says. Harris lives in Washington, D.C., and is a three-time winner of the AAAS Science Journalism Award. Rigor Mortis (Basic Books) is his first book.

Tell us about your science background.

I have an undergraduate degree in biology, which is how I first learned about biology, genetics, biochemistry and--most importantly--the scientific method. As a college student, I discovered that I loved learning about science, but I didn't particularly enjoy life in the lab.

Therefore, writing?

Science journalism was the perfect career for me. I started it right out of college with a fellowship, then a job at a small newspaper. I never looked back. My perch in journalism provides me the perfect vantage point to keep learning and watching as scientific knowledge evolves. Of course, the world has changed a lot since my degree more than 30 years ago.

Why a book about biomedical research?

In 2014, my beat at NPR shifted to biomedical research. In the course of orienting myself to the lay of the land since I'd last reported on these topics, I discovered some unfortunate trends--especially a push toward hyper-competitiveness as more scientists found themselves vying for a shrinking pool of resources. I started to explore the impact of that on research and realized there was a book's worth of material. At the same time, scientists were increasingly becoming concerned that many research results couldn't be reproduced in other laboratories. The two issues are deeply connected.

The book offers a plethora of information.

I had an outline going into the project, but of course it morphed as I did the reporting for the book. I knew from the outset that I wanted to explore the various reasons behind the lack of rigor in biomedical research, starting with dubious ingredients, and including unconscious bias, poor use of statistics and the perverse incentives in biomedicine right now (driven by the struggle for funding). I also wanted to take time to explain how science really works, and why failure is an inevitable--even beneficial--part of it. I also kept my eye out for scientists who were exploring ways to address these problems.

Did you learn anything surprising in writing the book?

Going into the project, I thought scientists might be reluctant to talk to me about the less-than-flattering issues confronting their profession. I was surprised that was not the case--almost everyone was eager to talk, not only about what's wrong, but why. As a reporter, I had been aware of the power dynamics within science, but those issues were generally peripheral to whatever specific topic I was covering, not the focus of my reports. The book gave me an opportunity to look at these issues directly--and to talk about them with some of the nation's most talented and influential scientists.

Would you say that money is the driving force in the biomedical industry?

Money plays an important role, but it's not the only driving force. I think far too often scientists become enamored with their own ideas and look for ways to bolster their theories instead of looking for ways to challenge them. That's absolutely human nature; we all do that, often unconsciously. But science, when done properly, is supposed to be a system that prevents people from fooling themselves. It works in the long run, but not so well in the short run.

You state that the "rate of new-drug approval has been falling since the 1950s." Is this a result of the biomedical community or the FDA?

This is not at all a problem of bureaucracy. The FDA drug approval process has never been faster. Part of the reason for the slow pace is that drug companies solved some of the easy problems early on, and now they're working on harder ones. You know the cliché about low-hanging fruit--well, it applies here. Another problem is drug companies largely stopped doing their own basic research and have come to rely heavily on academic science for leads. When academic scientists produce results that drug companies can't reproduce, that leads to false starts and wasted effort. That phenomenon contributes to the downward trend in new-drug development as well.

How could biomedical science be improved?

It could be much improved if researchers spent more time questioning their own beliefs. Unfortunately, the competitive nature of science and science funding often provides a disincentive for scientists to say, "maybe I'm wrong."

Rigor Mortis underscores the fierce competition and politics (on all levels) prevalent in the biomedical research field.

Competition has become fiercer--and for good reason. A decade ago, about 30% of NIH (National Institutes of Health) grants got funded; today it's about half that, due to an increase in scientists seeking money and a 20% decrease (adjusting for inflation) in the amount of funding available. Scientists are locked in an unhealthy struggle. Unfortunately, young scientists who may have the freshest ideas are often the ones edged out in this competition. They leave the world of research to the senior investigators who are able to draw funding because of their reputations. At this point, there's little hope of infusing enough new money into science to right this imbalance. These deep structural problems have no obvious solutions. It's going to get worse before it gets better.

Does that mean you're pessimistic about the future of biomedical research?

Despite the lugubrious title of my book, I'm optimistic about the problems I write about. No scientist wants to waste his or her time, and the community as a whole is becoming aware of its flaws. There were similar problems with medical studies involving human volunteers in earlier times. During the 1990s, scientists and funders turned their attention toward those issues and have made significant improvements (of course, there's always room for more) in the conduct of clinical research. The same can easily happen in biomedical research if the right incentives are put in place.

Who is the ideal reader for this book?

Rigor Mortis is written for the same audience that listens to NPR's science reporting--people who are curious about the world around them and who want a deeper understanding of how the scientific enterprise works. Science has been a driving force in our lives, helping us to understand the remarkable world we live in, while providing us technologies that make our lives better. This book is for people who want to understand the very human process behind all that wonder. I also hope that scientists who are trying to figure out how to make their enterprise more productive and less error-prone will find insights in reading Rigor Mortis.

Did any books inspire you in writing Rigor Mortis?

One of the greatest joys about writing a book was having the time to read other books along the way. I drew inspiration from The Invention of Science: A New History of the Scientific Revolution by David Wootton; Willful Ignorance: The Mismeasure of Uncertainty by Herbert Weisberg; Failure: Why Science Is So Successful by Stuart Firestein; A Conspiracy of Cells by Michael Gold; The Rise and Fall of Modern Medicine by James Le Fanu; and Consilience: The Unity of Knowledge by E.O. Wilson. --Kathleen Gerard

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