Review of “The Truth in Small Doses” by Clifton Leaf

Last December, for the first time, I attended the San Antonio Breast Cancer Symposium as a patient advocate. Each year, thousands of oncologists and cancer researchers go to this event to hear about advances in breast cancer research and breaking results from important clinical trials.

I was excited to be attending, but was soon struck by the contrast between the enormous gains that are being made in understanding the biology of breast cancer, and the slow progress in translating these remarkable findings into clinical application. Reading Clifton Leaf’s book, “The Truth in Small Doses: Why We’re Losing the War on Cancer–and How to Win It,” has given me some food for thought as to why we may be facing this situation.

Clifton Leaf is an award-winning journalist and editor who is also a cancer survivor and an advocate. With a background as a business editor, he started out ten years ago to investigate and write about how the “long war on cancer was being won on multiple levels.” But he quickly became convinced that what was being touted as a success was in fact more of a losing struggle.

Leaf begins the book with some perspective on cancer mortality numbers. He explains how some of the statistics that are cited can be misleading, depending on how they are used. He notes that the standard age-adjusted death rate is helpful for making comparisons between different regional and ethnic groups. But its use in describing trends in the same population over time obscures the full impact of the disease. The number of total annual deaths from cancer has grown at a much faster rate than the U.S. population over the last forty years and is now approaching 600,000 each year–pretty hard to square with the notion that we’re winning this “war”.

Leaf’s central thesis as to why the war against cancer has become a losing effort is that it has been plagued from the start by a lack of organization and direction.

There are numerous examples in the book of the fallout from the absence of meaningful coordination. One that was particularly striking to me was the discussion of the failed effort to identify “biomarkers” in the blood, urine or saliva that would be early indicators of developing cancer.

Leaf notes that, since 1990, more than 150,000 studies of would-be cancer biomarkers have been published. Yet these have not led to a single FDA-approved, diagnostic molecular-based test for cancer. An effective biomarker could form the basis for a strategy of “preemption”–in other words, identifying and treating preinvasive lesions before they become cancerous. Leaf clearly acknowledges and goes into some detail about the serious challenges around this effort,  but he goes on to say this:

Such daunting factors, however, do not mean that the idea of preemption is doomed from the start. Rather, the failed biomarker hunt demonstrates how poorly the search has been organized thus far. Indeed, there has been no actual search to begin with. Teams of volunteers have not walked arm-to-arm through the molecular woods, so to speak, as if looking for the body of a missing person. There has never been any real coordination of research teams or systematic follow-up on promising candidate markers. No one has been charged with the responsibility of leading the hunt–of saying, “Hey, you go this way, and I’ll go over there.”

Here are a few more of the thought provoking details I took away from this book–

New drug therapies: Despite the constant barrage of media headlines about new cancer breakthroughs,  just twelve new drugs were produced from 1990 – 2002 that were shown to extend the lives of any group of cancer patients even by weeks or months.

Research grant topics:   The decision-making apparatus around most research funding has evolved to favor low-risk research. As a result, tens of thousands of papers have been written on small aspects of individual genes involved in cancer.  Yet, we still we don’t know enough about these signaling pathways to be able to come up with therapies to intercept them.

Funding for researchers: Researchers have been forced to devote an ever great share of their time to the grant application process with grant success rates at the National Institutes of Health (NIH) down to only about 18 percent in 2011, compared to 41 percent back in 1972. And for younger scientists, obtaining grant funding has reached a crisis stage. Only one in ten NIH research project grants are awarded to a principal investigator under the age of forty, compared with four in ten in 1980.

Clinical trials:  Delay is built into every stage of the clinical trials process. A 2010 report from the Institute of Medicine found that 40 percent of NCI-sponsored Phase III clinical trials take so long to get going that they are never completed, leaving the treatment questions they were supposed to address unanswered and the patients who volunteered for them in limbo.

Tissue biobanks: It is estimated that there are hundreds of millions of tissue specimens from cancer patients in U.S. repositories today. Yet, scientists face a serious shortage of appropriate tissue samples for research. That is largely because there is no common set of standards for preserving and documenting specimens.

Leaf makes it clear there are no “villains” in this story. And it isn’t that these problems have been hidden, he points out. In fact, they’ve been well known for a long time by leaders in the research and medical community, but little has been done to resolve them. He explains that the problem lies in the “culture” around cancer research. It is a culture, he says, that is characterized by extreme risk aversion, but that, at the same time, ignores the risk of inaction.

Changing that culture, Leaf says, means realigning the funding system with the right goals, including rewarding innovation and having scientists spend their time doing science. Other urgent changes in his view include paring the “multiple layers of decision-makers that preside over nearly every aspect of the cancer research process” and building a common language and research infrastructure “that can help transform tens of thousands of separate laboratory fiefdoms into a critical mass.”

This book is thoroughly researched and is also easy to read. There are extensive references provided in notes for each chapter at the end of the book. It provides some valuable insights about what we need to do to get on track toward finding new treatments that do save lives in greater numbers and finding ways to intervene early enough in the disease process to prevent full-blown cancers from developing in the first place.