The Great Prostate Hoax
How Big Medicine Hijacked the PSA Test and Caused a Public Health Disaster
By Richard J. Ablin, Ronald Piana
St. Martin's Press Copyright © 2014 Richard J. Ablin and Ronald Piana
All rights reserved.
Great doubt: great awakening.
Little doubt: little awakening.
No doubt: no awakening.
— Zen Maxim
Power is the ultimate aphrodisiac.
— Henry Kissinger
It would come to me several years after I discovered PSA, an internal stirring that something I was part of was going terribly wrong. A scientific sleight of hand had recklessly sparked a destructive wildfire of false hope in our health system — I knew it would be near impossible to confine, let alone put out. If it had but one name I'd call it potestas, Latin for power. Money usually plays a leading role in abuse-of-power stories. It does in the one you are about to read.
I never imagined how society's collective mind could be warped by fear until my days as a US Agency for International Development Research Consultant in Asuncion, Paraguay. I was there investigating better ways to diagnose and treat Chagas disease, which is caused by the protozoan Trypanosoma cruzi and vectored to humans by the parasitic "kissing bug," Triatoma. My work took me from a laboratory at the University of Asuncion out to sun-scorched rural areas where locals guided me through mud-hut villages festering with Triatoma.
At that time, Paraguay was clenched in the iron grip of the military dictator Alfredo Stroessner. My associates at the lab confided that Stroessner, paranoid about a leftist coup d'état, had his thugs spirit away suspected communists, shoving them out of airplanes soaring thousands of feet above the obliterating jungle.
Monsters like Stroessner won't appear again in this story. But you will meet powerful men in white lab coats who manipulated our medical system for personal gain and self-aggrandizement, setting in motion a self-perpetuating industry that has maimed millions of American men — and continues to do so.
Our scientific and medical history tells us, among other things, that actions based on contrived evidence and the people behind those actions can grow old together unless exposed with a loud enough voice. The word science is derived from the Latin scientia, meaning knowledge. What good is knowledge without evidence?
After finishing my work in Paraguay, I returned to the States and completed my US Postdoctoral Fellowship in the internationally renowned Bacteriology and Immunology Department at the University of Buffalo School of Medicine. It was 1968, a fiery year — the Vietnam War was still raging, Martin Luther King Jr. was gunned down at a motel in Memphis, igniting nationwide riots, and Richard Nixon's obsession with winning the presidency was consummated. Challenging social norms was the zeitgeist of the late sixties and for a young immunologist consumed with investigating the hidden structure and function of cells there has never been a freewheeling time like it.
Scientific research is a rigidly disciplined process, but serendipity has long played a role in notable careers and discoveries, as it did in mine. In short, my postdoctoral mentor traded me to the Millard Fillmore Hospital Research Institute (an affiliate of the University of Buffalo School of Medicine), for a fluorescent microscope he needed for his own lab. The gist of the deal was, "Give me a fluorescent microscope and you can have Ablin." Of course, the details of that swap were more complicated, shrouded in academic intrigue that I won't retrace. After the microscope was delivered, I joined the institute and worked with two urologists, Drs. Ward A. Soanes and Maurice J. Gonder. As it turned out, Soanes and Gonder had a generous grant from the John A. Hartford Foundation funding their studies of the normal and abnormal prostate gland. Being traded for a microscope worked out just fine.
Soanes, who co-owned several private hospitals, was a snazzy dresser who tooled around the city of Buffalo in a Rolls-Royce Silver Shadow. His more conservative counterpart, Gonder, was a square-jawed man with a military bearing. Cosmetic differences aside, the two urologists had developed cryosurgery — now known as cryoablation — and were investigating its then novel role in prostate cancer, which I found a captivating line of scientific inquiry.
At first we experimented with cryosurgery on the prostate of rabbits and rhesus monkeys, in which we observed an interesting immune response. As the research progressed, we began treating the prostate of cancer patients with cryosurgery; several men had advanced disease that had spread to distant areas such as the lungs and cervical vertebrae. Following their cryosurgery, I witnessed a spellbinding phenomenon — distant tumors had regressed; in some cases all of the patient's cancer had vanished.
Naturally, I wanted to know how freezing the primary tumor enacted such an explosive immune response, for which I coined the term cryoimmunotherapy. I went seeking an answer. The lab animals we treated with cryotherapy had an immune response to antigens of the frozen tumor tissue. Since I saw similar responses in men with prostate cancer, I hypothesized as one possible explanation that the frozen-tissue destruction might have liberated a prostate cancer-specific antigen responsible for the cryoimmunotherapeutic effect.
Sensing a breakthrough, I immediately launched a series of immunologic studies of the normal, benign, and malignant human prostate and secretions to determine whether a cancer-specific antigen was at work. I could not find one (I, along with others, am still looking), but I did discover a prostate tissue-specific antigen — PSA. The year was 1970.
THE "DOCTOR" DOTH PROTEST TOO MUCH, METHINKS
In 1953 two scientists, James Watson and Francis Crick, sauntered into the Eagle Pub in Cambridge, England, and announced they had found the secret of life: DNA. From antiquity until the present, scientific discovery in many instances has always been a messy affair of unrequited recognition. Not surprising, a nasty dispute over Watson and Crick's discovery still surfaces in the national press every so often. I didn't discover the secret of life, but my discovery of PSA as a biomarker is noted as a major scientific advance. As with DNA, PSA has not been immune to controversy. For several decades, a coterie of powerful doctors has tried to discredit my discovery. Since their compulsion to silence my message about PSA screening is a core element of this book, I'll clear the issue up before moving on.
I left Buffalo in mid-1970, moving with my wife, Linda, our son, Michael, and our Irish Setter, Deacon, to Springfield, Illinois. There, I headed up the immunological component of a developing renal transplant program at Memorial Hospital of Springfield in affiliation with the Southern Illinois University School of Medicine. In early 1973, on the invitation of two urologists at Chicago's Cook County Hospital, I had the opportunity to return to my research on the prostate and we all moved to Chicago, where I began a ten-year stint at Cook County Hospital and the Hektoen Institute for Medical Research.
Nothing notable happened in the PSA story until 1979, when a group from Roswell Park Cancer Institute (RPCI, located in Buffalo, New York)published a paper in the journal Investigative Urology claiming the discovery of PSA. One of the paper's authors, T. Ming Chu, contended that his PSA was different from mine. It doesn't serve this book's purpose to delve into dense scientific analysis over the antigens, but for clarity it is important for the reader to understand that PSA, no matter who discovered it, is not cancer-specific — therefore it cannot not detect prostate cancer. That is a critical point to grasp as we move forward, because it is the lynchpin of my argument against using PSA to screen healthy men for prostate cancer. In chapter 3, I'll make my position clear, using a set of easy-to-understand principles I call the four cruxes.
The dispute with Roswell Park has been publicly debated in letters to the editor and commentaries across multiple journals, which ultimately proved nothing, settling like windblown ashes on a cold fire. Today the firm consensus among the scientific community is: in 1970 Ablin initially observed PSA; in 1979 Roswell Park's Chu and other researchers set out to extend Ablin's initial discovery by purifying and characterizing PSA and subsequently developing the PSA test.
I have never challenged that narrative, only the misuse of the molecule that I discovered.
In 1984 Roswell Park received a patent for an immunoassay blood test in prostate cancer. The technology was transferred to the biomedical industry, a clumsy handoff during which the nuanced benefits of PSA (discussed in later chapters) were cleverly distorted into a prostate cancer-screening tool and mass marketed to eager but uninformed doctors and their patients. In Chu's own words, "Things started happening quickly after that." They certainly did. In the next chapter I'll flash forward two years to a critical juncture and explore how the clinical truth of the PSA test was either manipulated and or disregarded by the biotech industry, the US government, and the urology community.
A bit about Roswell Park Cancer Institute. It is difficult for the lay reader to comprehend the embedded power in an institution such as Roswell Park. Its designation as the first National Cancer Institute (NCI) Comprehensive Cancer Center distinguishes Roswell as a crown jewel in our $3 trillion-per-year health care system. For decades, doctors in this powerful bully pulpit have consistently silenced, by dint of their authority, any challenge to their dogma on PSA screening. For example, in September 2012 Roswell's president and CEO, Donald L. Trump, MD, and its chair of urology, James Mohler, MD, using the age-old practice of casting doubt on the messenger to cast doubt on the message, wrote a tortuous, condescending letter to the editor of The ASCO Post in an attempt to discredit my discovery of PSA.
More disturbing is their use of the unjustified fear of cancer as some kind of human shield to protect their position, stating that my and the US Preventive Services Task Force's strong recommendation against PSA screening in asymptomatic men would "certainly return us to the days when most men ... were likely to die a long, painful death from [prostate cancer]."
Although the moat protecting the PSA fortress is beginning to dry up, its defenders still man the parapets. Otis Brawley, MD, a prominent oncologist who is the chief medical officer of the American Cancer Society, was once a proponent of routine PSA screening. But over the past several years, Brawley has modified his view, becoming skeptical of tactics used to push mass routine PSA screening, saying that he's "against lying to men ... exaggerating the evidence to get men screened." To Brawley's heresy Mohler responded, "I have known Otis for over 20 years. He doesn't come off as being ignorant or stupid, but when it comes to prostate-cancer screening he must not be as intelligent as he seems." It is worth noting that Mohler, who is very high up on the political food chain in the health care industry, chooses his words with care.
Trump and Mohler, and others you'll soon meet, may continue their efforts to discredit my role in the PSA saga and challenge others who share my opinion. But my message is based on science, not self-serving rancor: routine PSA screening does far more harm to men than good and the potential harms can be crippling and life-changing.
As Susan Sontag wrote in her classic work Illness as Metaphor, "The controlling metaphors in the descriptions of cancer are, in fact ... drawn from the language of warfare." We officially began our war in 1971, when Richard Nixon signed the National Cancer Act, which was the opening salvo in the so-called War on Cancer. Waging war gave the people an enemy, something to rally around. Jingoism might have its place in actual war, but not in medicine — evidence should always trump emotion. A gold-rush mentality to embrace the next greatest medical breakthrough can, as in the PSA test, have dire consequences.
The timing for mass marketing was perfect. Promising studies in breast mammography fueled a national explosion of cancer screening. The feminist movement brought discussion of breast cancer out of the closet. Advocacy groups, led by formidable women, lobbied on Capitol Hill for universal breast cancer screening. The mantra "early detection leads to cure," chanted by breast cancer advocates, would soon be embedded in our national consciousness. By the early 1980s men had grown restless for their own early detection tool. Prostate cancer had a visceral grip on men akin to that of breast cancer on women; it spoke directly to gender-based fear of premature mortality and struck at the core of manhood. Men would begin to form their own advocacy groups, using celebrity prostate cancer survivors as spokesmen.
As the screening storm kicked up, the emerging biotech industry and the urology community focused their collective energies on an irresistible financial opportunity: 30 million age-appropriate American men. The word campaign — with its militaristic connotation of confronting an enemy — was rolled out like tanks by the marketing machines that ginned up the prostate cancer business model. Stakeholders from major cancer organizations to the federal government — for example, in 1999 the Postal Service issued a stamp advocating annual PSA tests — tacitly urged on the campaign by turning a blind eye to an uncomfortable scientific fact: I tried to explain that PSA does not detect prostate cancer simply because it is not a cancer-specific marker. Even its most ardent proponents don't challenge that scientific fact. In pages to come, I'll break the PSA test down to its constituent parts and illustrate the downstream clinical effects its routine misuse has on men and the unvarnished human realities of unnecessary procedures.
To illustrate a critical theme of this book, I'll tip my hat to Sontag's war metaphor. Doctors need tools to diagnose illness. Patients wait nervously for the results of the diagnostic tests their doctors order. Unfortunately, our diagnostic technology does not always tell the clinical truth. It can produce a false negative (the test missed detecting something, such as a tumor) or, more likely, and more pertinent to this story, a false positive (indicating a condition that does not exist, such as cancer).
In 2003, while the country was still cocooned in post-9/11 fear, the United States made war on Iraq. History will judge that aggression. However, using the war as a medical metaphor serves this story well. In making the case to the American people, the Bush administration and the lay press referred to Saddam Hussein as a cancer whose weapons of mass destruction (WMDs) would metastasize throughout the region, eventually to our shores. Surveillance planes (think PSA screening) picked up what was roundly purported to be evidence of the vaunted WMDs. Of course there never were any WMDs. The urgent need to wage war was emotionally based on a monumental false positive that was sold to an American public still numb from the catastrophe on 9/11.
The way the PSA test has been misused for more than three decades amounts to the most damaging false positive in American medical history. How could we reiterate a medical blunder for 30 years? When powerful people repeat an idea often enough — even when it is false — a mind-blunting form of authority is established, and getting there can be an alarmingly swift process. Confronting the imbedded medical authority is where the battle over the trust and value of American health care might very well be won or lost.
A DECISION I THOUGHT I COULD LIVE WITH
It is a predisposition of human nature to consider an unpleasant idea untrue, and then it is easy to find arguments against it.
— Sigmund Freud
Has there ever been a society that has died of dissent? Several have died of conformity in our lifetime.
— Jacob Bronowski
On a rainy October night in 1979 I was catching up on my reading when a paper in the journal Investigative Urology, "Purification of a Human Prostate Specific Antigen (PSA)," caught my attention. I wasn't surprised to see that the authors were from Roswell Park Cancer Institute. Over the years — despite the controversy over whether I or Roswell's T. Ming Chu actually discovered PSA — I'd considered Roswell's investigations on the antigen as a theoretical curiosity, not fully sure of their endpoint. I dwelled in a simple academic ethos: you make a discovery, you publish a few journal papers, you move on. However, a follow-up 1980 article in the journal Cancer Research indicated that Roswell had grander ambitions for the molecule I first observed in 1970.
Although concerned about the grave potential for misusing PSA, at that time I was absorbed with, among other things, my research in immunotherapy at Cook County Hospital in Chicago. But as PSA screening began rolling out across America, I felt as though I were rubbernecking one of those multivehicle disasters in which dense fog sneaks up and blankets a stretch of highway. Cars, one after another, ram into each other, setting off a massive chain reaction crash. The full damage can only be calculated after the weather clears. (Continues...)
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