Bad Blood. A review.

My blog, The Weekly Packet, (https://theweeklypacket.com/category/health-care/ ) of April 30, 2016 ran under the title “The Theranos evidence, waiting for a story.”

In the text, I said, “… looking at the facts is like looking at individual organs at an autopsy, after the diener has washed them, weighed them, and put them in clean pans. What we need now is the pathologist to come in, and with knowledge and experience, he or she will tell the story that puts the facts together into a coherent narrative. At some point, the narrative may well make an instructive case study.”

John Carreyrou’s new book, Bad Blood: Secrets and Lies in a Silicon Valley Startup, tells the story with spellbinding skill and detail. Those of us who had some background, however minimal, in laboratory work knew that Theranos had almost certainly over-promised and under-delivered. None of us knew the details.

Carreyrou’s reporting reveals the astonishing extent of the process in a marvelously “coherent narrative.” He details the scope of the deceptions involved, including misleading deals with Walgreen’s, Safeway and even an attempt to involve the army, the vast sums of money lost, and the lives disrupted.

First, no spoilers. Read the book! Then, after the mesmerizing read comes the hard part: what can we learn from this story?

One obvious lesson relates to corporate culture. A corporate culture that encourages tough questioning across disciplines and insists on facts may sometimes seem harsh. In such an environment, though, mutual respect and civility make the system work. What we see in Bad Blood, though, is the destructive effect of siloing and secrecy. And we see that destructive process emanating from the top levels of management.

There’s another lesson, too. A very old one. Making the error of hubris provokes the outcome of nemesis. David Ronfeldt explained in his excellent essay for the Rand Corporation, “Beware the Hubris-Nemesis Complex: A Concept for Leadership Analysis.”

“In Greek literature, hubris often afflicted rulers and conquerors who, though endowed with great leadership abilities, abused their power and authority and challenged the divine balance of nature to gratify their own vanity and ambition. Thus hubris was no common evil: It led people to presume that they were above ordinary laws…”

He continued on,

“Hubris above all is what attracted Nemesis, who then retaliated to humiliate and destroy the pretender, often through terror and devastation. Thus she [Nemesis] was an agent of destruction. The battle won, she did not turn to constructive tasks of renewal and redemption—that was for others to do. Yet her behavior was never a matter of pure angry revenge. There were high, righteous purposes behind her acts, for she intervened in human affairs primarily to restore equilibrium when it was badly disturbed, usually by figures who attained excessive power and prosperity.”

With Bad Blood, John Carreyrou has written not just a stunning piece of non-fiction reporting, but a cautionary tale for our times.

Ink still damp from the press

Back in the 19 century, there must have been times when the weekly packet boats had just started to slip the moorings. Then a young boy came running down to the wharf and tossed the very latest newspaper on board, ink still damp from the press.

That scene describes how I feel watching the evolution of articles in the staid pages of JAMA, the Journal of the American Medical Association, and other AMA publications.

For decades, through the 1970s well into the 2000s, the AMA seemed to have a multiple personality disorder. Politically, the organization represented the views of conservative private-practice oriented white male physicians, while the editorial views of JAMA were blatantly ultra-liberal and anti-pharmaceutical industry. Now, the journal and the other organizational media seem to be making a real effort to deal with issues that occupy the interface of society and organized medicine: opioids, income inequality, and environmental- public health concerns including air pollution and water quality.

My experience as the medical director of a heart transplant program taught me firsthand that public health and prevention are far more effective for the population at large than high-technology approaches to end-stage disease. Now, from the AMA of all places, we seem to be witnessing the same realization taking hold. So, I feel like the youngster tossing the fresh newspaper aboard when I tell you about a really worthwhile read in the April 24, 2018 issue of JAMA titled “Health, Faith, and Science on a Warming Planet.” (JAMA. 2018;319(16):1651-1652.) The authors are Monsignor Marcelo Sánchez Sorondo PhD, of the Vatican’s Pontifical Academy of Sciences, Howard Frumkin MD DrPH, from Environmental and Occupational Health Sciences, University of Washington School of Public Health, and Veerabhadran Ramanathan PhD, Atmospheric and Climate Sciences, Scripps Institution of Oceanography.

This astounding trio opened their article by stating, “Climate change, altered natural cycles, and pollution of air, water, and biota threaten the very conditions on which human civilization has depended for the last 12,000 years. While human health is better now than ever before in human history, climate change is undermining many public health advances of the last century and ultimately may be associated with the unprecedented extinction of species. The increasing gap between the wealthy and poor—already unconscionable, and the cause of profound preventable morbidity and mortality—amplifies the effects of climate change on health and deepens health disparities.”

This message, the news that has me running to the dock, is that this is an establishment voice —JAMA, for heaven’s sake— announcing a new paradigm that aligns public health, environmental issues, and economics in a new view of civic and social engagement. This is big news.

Here are the six main points from the paper:
1. Disciplined, critical thinking, and an unfailing commitment to distinguish what is verifiable from what is not, characterize the best of the health, science, and faith communities.
2. Scientific evidence is a primary basis for distinguishing what is verifiable from what is not.
3. With unchecked climate change and air pollution, the very fabric of life on Earth, including that of humans, is at grave risk.
4. There is a role for reverence and awe.
5. There is a moral obligation to safeguard the earth for future generations
6. There is a moral obligation to care for the most vulnerable.

Take a deep breath, and resolve to become, or to remain, engaged.

 

 

 

Photo is the interior of the Metropolitan Cathedral in Buenos Aires, where Pope Francis, as Archbishop Jorge Bergoglio, used to perform mass. (KZM photo, Mar. 14, 2014. Sony DSC-HX300. 1/25th at f2.8, ISO 800)

Perspectives on my 50th medical school reunion.

In 1682, William Penn, an English Quaker, founded the city of Philadelphia as the capital of his Pennsylvania Colony. 83 years later, in 1765, Drs. John Morgan and William Shippen convinced the Trustees of the College, Academy, and Charity School of Philadelphia to found the first medical school in the then-colonies on the eastern seaboard of North America—modeled on the University of Edinburgh, where they had trained. When the Medical School was founded in 1765, the College and the Medical School became a university, although the term “university” was not added to the institution’s official title until 1779.

At the first commencement, June 21, 1768, ten medical students received their M.B. degrees. (The College granted the first M.D. degrees to four of these men in 1771.)

Two hundred years later, in 1968, my class graduated from that same medical school at the University of Pennsylvania, and last weekend, 250 years later, we celebrated our fiftieth reunion. Perspective comes from such an event.

Individual lives, and deaths, occur. The patients, the teachers, and some of the classmates from whom and with whom we learned so much are gone. Soon we—with all the fragile neuronal connections that we treasure as our professional knowledge and skills—will also return to the dust. But the institution continues. What most concerns our class now is what that institution will look like after another half-century.

Philadelphia and its 1.5 million inhabitants could be vaporized in a thermonuclear holocaust, could be flooded by warm rising seas, or could fall victim to some other unpleasant end. But for the foreseeable future, our civilization, the city, and the university will most likely muddle on.

What can’t muddle on is our way of doing health care. From my experience in the US Navy and from visits to institutions all across the country representing Janssen Pharmaceuticals, I know that good medical care does not require the opulence, the cavernous spaces and grand edifices, that we see in major hospitals today.

What do we need to really do our work as doctors? Accessible simple, sturdy well-lighted buildings with good heating and cooling – easily cleaned surfaces – basic hematology, chemistry, and microbiology labs – a couple of reliable X-ray machines – a delivery room and an operating room – a few rooms for overnight stays –a basic food-service operation— a functional record system – a well-stocked pharmacy – high-speed internet, that’s all. Oh yes, and a place to send the patients when that simple facility can’t handle their problems. No questions asked.

What I’m describing could exist. Should exist. If we had a system where every person in the country had low-cost insurance to cover basic immunization and preventive care, maternity care, trauma, and out-patient primary care, then such places would exist. They would provide the network of referrals that research universities and their academic medical arms must have to do their work.

Every single one of us has benefited from what Penn, Harvard, UCSF, Stanford, and the other 137 accredited MD-granting institutions and 31 accredited DO-granting institutions in the United States do. We should help to fund them through taxes, grants, gifts, and health-care insurance that helps to pay for their services.

But we would also all benefit from extending basic care to our whole population. Make no mistake, breakthroughs in science will come; brilliant younger people are hard at work in their labs. My hope, as I left Philadelphia, was for progress in how we deliver care.

shutterstock_348308990

I Love It When a Plan Comes Together

weeklypacket

Imagine a half-dozen or so college students in hip boots, brandishing wide nets and paper punches, invading your quiet, secure home. Fortunately, fish don’t think much at all, so the fish in the woodland pond that my ecology class visited back in 1963 probably don’t recall our visit to their ancestors, but I still do.

We set out to calculate the number of fish in the pond. The method required catching and counting a sample of fish, hence the nets. Then we marked them with a small, neatly punched hole in the thin membrane of their tails and carefully released the known number of marked fish (= M1) with detailed instructions to go and mix-and-mingle with their companions for a week. (Indicator dilution, for you purists.)

One week later, back in the hip boots, we netted a new sample and counted those with (=M2) and without (=M0) tail punch marks. With this much information, we could calculate the number of fish in the pond:
If x = number of fish in pond
Then M1/X = M2/M0 and the rest is algebra.
This was my favorite experiment in all my academic experience. Imagine getting OUTSIDE in HIP BOOTS and doing something scientific. Like a stonefly emerging from the depths of the library, I turned into an environmentalist.

Stay with me for just a few more minutes. As an almost-ten-year-old growing up in northeast Ohio, I remember the November 1952 picture of the Cuyahoga River on fire that ended up in Time Magazine a month later – a truly arresting image showing flames leaping up from the water, completely engulfing a ship. Over the years, as a physician, I’ve followed the stories of various health problems that seem to have had roots in the environment; Dan Fagin’s Toms River is one of the best. A few years ago, I first read Steven Johnson’s marvelous book, The Ghost Map, the story of John Snow and the London cholera epidemic of 1854.

Then, just this morning, I had a real “Ah-ha!” moment. I read Margaret Talbot’s New Yorker article (The New Yorker, April 2, 2018), “Scott Pruitt’s Dirty Politics,” and my son David, an environmental economist, sent me a piece from the American Public Health Association on environmental health.
“Many communities lack access to nutritious, affordable food; are denied safe           places to walk and exercise; or live near polluting factories. The health risks for these families are greater. We support research and action to help ensure healthy environments for all.”–APHA Executive Director Georges Benjamin

All of these issues are related. It all comes together!

We are not separate from the environment. In populated areas, we ARE the environment, or at least, the environment is largely man-made.

Some individuals with political power do not seem to understand the connection between environmental health —clean air, clean water, open spaces— and human health. Those individuals will not be swayed by facts. In fact, they actively reject science as a basis for public policy.

For now, we can support the public organizations that do battle on behalf of the environment, particularly those that wage their battles in the courts. And soon, we can, we should, we must…VOTE.

PS: The photo this month is an outhouse in the Chinese section of Arrowtown, New Zealand. The Chinese, who came to New Zealand as gold miners, were keenly aware of the importance of sanitation.

“Medicalization”

EPSON DSC picture
 

I have just carefully read through several editorials in the January 16, 2018 issue of JAMA, the Journal of the American Medical Association. This issue reflects a growing enthusiasm among medical editors for what’s generally called a “focus issue.”

Since I’m not an editor, I have only a vague idea of how this works. In my mind’s eye, I see the editor sitting at a very large, cluttered desk with accepted but unpublished manuscripts piled by subject. As a pile grows to a threshold size, say seven and three-quarters inches, the editor says, “Aha! A focus issue.” Then he or she gathers up the pile and says to the staff, “Print all these together in 6 or 8 weeks, and we’ll be done with them.”

Readers know that I have no intention of writing about the focus of the issue, which happened to be obesity. What I do want to reflect upon are the social changes that have moved obesity from a straightforward statement about body composition to a medical problem worthy of a focus issue of JAMA, arguably one of the most prestigious medical journals in the world.

When I was a kid, turning to a dictionary definition of the assigned subject provided an easy “out” for starting an essay. I hope I’ve become a bit more sophisticated; now, I’ll turn to Harvard Magazine instead. I quote from the issue of April 23, 2009: “There are perhaps few academic topics of equal interest to scholars of history, law, anthropology, neuroscience, and literature. But this was part of the point when scholars of these disciplines gathered on April 22 for a symposium on medicalization—a phenomenon, they argued, that has infiltrated nearly every facet of modern life.” Not exactly stirring prose, but I’m sure you see the point. Or do you?

Beginning roughly in the mid-1970s, when faced with really tough social-behavioral problems, particularly those that have serious health consequences like alcohol abuse, drug addiction, and obesity, Western society has declared them medical problems.

This process, “medicalization,” relieves broad swaths of professionals from dealing with insoluble problems. Physicians, however, seem to willingly accept the process. We seem to say, “Give us your obese, your addicted, your anxiety-ridden… Send these to my clinic, to my hospital, I lift my stethoscope beside the golden door.” Not only do we engage in this altruism, we campaign to make their diagnoses “official” and billable, and then try to find treatments.

Lest this sound a bit negative, the Harvard conference attendees catalogued the forces that help to drive the trend toward medicalization:

  • “the very existence of health insurance (costs are only reimbursable when associated with a definable medical condition
  • death certificates (the need to give a name to what caused a person’s death)
  • research funding (funding is more likely for problems defined as diseases)
  • drug trials and approval
  • and even a desire to wash one’s hands of blame for one’s condition (for instance, by considering obesity a disease that assails people rather than the result, at least in part, of one’s own actions and lifestyle).”

As I become more senior in the medical community, my awareness of the importance of communication, both among doctors and between doctors and patients, continues to grow. How long will the medical community continue to accept the process of medicalization before we say, “Look, we can help to manage the physical consequences of behavioral problems. If you are too heavy, we can replace your worn-out joints, get your cholesterol and blood sugar down, and help with your blood pressure. But we can’t modify your behavior; you have to decide to do that.”

What you see is what there is…

bfb-1-of-1

One of my medical school classmates recently posted a Washington Post article on Doximity, a “social media” site for physicians. The article caught my attention. I think it’s worthy of some comment. The author of the Post article is a brilliant young physician, Dhruv Khullar; his subject was a recent paper in JAMA by Denson, Jensen, Saag, et al. titled “Association Between End-of-Rotation Resident Transition in Care and Mortality Among Hospitalized Patients.” 

The primary finding from this large, retrospective, multicenter observational study was, “end-of-rotation house staff transition in care was associated with significantly higher in-hospital mortality.” The headline for the Post article was “When a new team takes over your care at the hospital, it can be a precarious time.” The change in titles itself is a pretty dangerous transition.

After 14 paragraphs describing the intellectual and emotional uncertainties inherent in teaching-hospital house staff transitions, Khullar finally wrote, “Patients who remain hospitalized during transitions may simply be sicker.” An editorial raising this issue, and the data in the JAMA publication from a restricted analysis that showed markedly lower mortality after attempting to adjust for the degree of illness, at last got some attention in the text.

Here’s my point. There is a critical feature that links all three pieces: the research paper, the editorial, and the Post article; they all acknowledge that the basic premise of the work is flawed, but all three then go on to propose solutions to the  undefined “transition problem” anyway.

Why do I suggest that the analysis is flawed? I’m not a statistician, but after decades of reviewing medical papers, I know enough to realize that this retrospective study was not a statistical problem of tossing fair dice. Patients who are or are not candidates for discharge from hospital on any given day differ in many ways. The study population was not randomized, and as the researchers commented, “the differences observed in patient populations might represent a direct consequence of clinical decisions made because of an upcoming transition rather than confounding. That is, if clinicians try to discharge as many patients as possible prior to transitioning off service, but have more difficulty discharging complex and long-stay patients, the average severity or complexity of patients exposed to transitions in care could be increased.”  [Italics mine]

An ad hoc attempt to adjust for these issues with an alternative approach to analysis demonstrated that the findings were highly dependent on unmeasured factors. As the researchers noted, “The increased 30-day and 90-day mortality risks observed in the main analysis suggest that the delayed discharge of these complicated patients following transition could be detrimental…   The alternative analysis, however, did not demonstrate these findings, [italics mine] which could be related to the noted differences between analyses.”

So, I would like to pose a really interesting question. Why did the authors (and the reviewers and editors) of all three pieces perceive a problem and then propose solutions to it in spite of the facts that the “adjusted” data suggested that the effect of house staff transition was not nearly as great as initially suspected, and that both the authors and the editorialists realized that, “Patients who remain hospitalized during a change in personnel on the inpatient service are likely different than (sic) those who are discharged”?

For the answer, I suggest we ask Nobel Prize winner, Daniel Kahneman. In his book, Thinking, Fast and Slow, Kahneman pointed out, “even compelling causal statistics will not change long-held beliefs…” In the transition-of-care publications authors, reviewers, and editors cling to the long-held belief that doctors can somehow overpower the poor prognosis of old age, frailty, and severe disease by improving the mechanics of healthcare delivery.

In our society, this belief encourages us to think about developing better hand-off forms for interns and residents instead of thinking about how we might really care for patients.

All’s not lost! These observational data do suggest a testable hypothesis. With an upcoming transition in care, rather than pushing early discharge for patients who are basically going to do well, a more productive approach might be to focus effort on recognizing the sicker patients and making appropriate arrangements for them, for example, earlier initiation of specialty consultations, social services for discharge planning, or consideration of hospice or palliative care transfers. In other words, one could randomize two large groups to either usual care (perhaps with the undeniably attractive hand-off forms) or pre-transition intervention starting a week or so before transitions and focused on appropriate discharge planning for sicker patients.

But then again, shouldn’t that be happening now?

P.S. The bird pictured is a blue-footed booby that Katherine photographed in the Galápagos Islands. I included it to make the point that blue-footed boobies do, indeed, have blue feet. This is directly related to the clinical concept that sicker patients do, indeed, do worse.

“Corporate Culture”

Atul Gawande, the Brigham surgeon and author, has a fascinating article titled “The Heroism of Incremental Care” in the January 23rd New Yorker magazine. His subject is the importance of good medical management over time. He writes, “Success, therefore, is not about the episodic, momentary victories … It is about the longer view of incremental steps that produce sustained progress. That … is what making a difference really looks like. In fact, it is what making a difference looks like in a range of endeavors.” He concludes that the corporate culture of healthcare must acknowledge, “The heroism of the incremental.”

The importance of careful process is a critically important subject that I tried to emphasize with house officers in training during my academic medical career. As readers of Nesiritide know, I carried that interest in process over to my work in the pharmaceutical industry as well. So, it may not surprise anyone that over a wee drop of very nice Scotch my neighbor, an upper-level manager in the automobile industry, and I fell into a talk about Volkswagen’s diesel emissions problems. I asked, “What went wrong at VW?” Which is how I ended up reading a fascinating article by Robert Armstrong in the Financial Times of January 13th.

After a review of the public-domain facts, Armstrong came to the conclusion that “something went wrong with VW’s culture such that immoral behavior became acceptable,” and he found this “an uncomfortable conclusion.” He went on, “I will confess I understand little about how corporate cultures work or how to improve them.”

Today, I talked with another friend, a businessman from Chicago, who had heart surgery at the Cleveland Clinic a few days ago. He was delighted to be feeling well and walking in the halls, but what he really wanted to talk about was the Clinic’s corporate culture. He said, “They really DO the patient-first thing here; everyone from the janitor to my heart surgeon does it.”

Corporate culture is about what the members of an organization believe about the enterprise and how they behave in both internal and external interactions. Leadership articulates the vision and values of the corporate culture and implements the practices of that culture.

I’ve been working with a group of college classmates on a project related to President Kennedy that’s driven in part by his 100th birthday this year. As President, he articulated a vision of the national “corporate culture” that asked citizens to participate in the great social enterprise. If we hope to get through the next few years, we must all get involved in defining our vision and values. Have a look at the website, watch the short video, and share your thoughts, please.

Health

I have been working, admittedly on-and-off, on a blog piece dealing with drug prices and “complementary and alternative medicine” (CAM) expenditures. Only something strange happened. The more time I spent with it, the less I liked it.

Initially, it was a reaction to a Consumer Reports article on drug pricing. As I’ve pointed out before, only a small fraction of prescriptions account for about a third of all drug spending in the US. In contrast, people spend billions every year on CAM, in the form of nutraceuticals, herbals supplements, and payments to alternative practitioners. So, it was a good case. Regulate the CAM folks, and use the savings to help pay for expensive drugs. The idea sounds like a campaign speech.

But that’s not a good case. It’s self-serving. At one level, it’s “tax the bad guys that I don’t like and give the money to the good guys who do clinical trials, aka the pharmaceutical industry.” It’s also an exercise in logical behavior that could not be expected from government. Most importantly, it completely overlooks the fact that individuals are involved in all these transactions. People, most of them very ill, find out that a drug that might help with a little relief or a little more time is extremely costly. People, often misled or ill-informed, decide to buy an herbal compound or to see a CAM practitioner. Like those of us who can’t resist a quick pick lottery ticket at the gas station, they are buying a small and short-lived parcel of hope.

As I think back to State Street Junior High, 1956, “health and physical education, third period M-W-F, Mr. Chester Riffle,” meant those were the days I carried my gym bag with shorts, T-shirt, socks, jock and a towel. Health education meant learning that if you don’t dry between your toes after a shower in the locker room, then you will get “athlete’s foot.”

As an aside, medical school is not a place to learn about health. Medical school is where you go to learn to call “athlete’s foot” by its proper name, tinea pedis. Medical school is about disease, not health.

I’m glad that I didn’t subject you to a rant about drug costs and CAM. I appreciate your patience with this alternative. Maybe, just maybe, there’s a need for a book about health. What do you think?

Signs of a health issue along I-75

Good afternoon, everyone.

The Weekly Packet will be getting back to regular sailing now that Nesiritide. The Rise and Fall of Scios has passed the final proofing and is on the way to the printer. Please look for the title as above on Amazon, or alternatively search by author: Roger M Mills, MD.

I have also been scrambling to get to a final draft of Clinical Management of Heart Failure, 3rd edition. The co-authors (Jim Young and Javed Butler) and I opted for starting the third edition with a clean slate. As a consequence, I have just made the long drive from our camp in Michigan’s Upper Peninsula to spend a day with Jim at the Cleveland Clinic. Which leads to what’s really on my mind.

On June 7th, JAMA ran an opinion piece titled “Lifespan Weighted Down by Diet” by David S. Ludwig, MD, PhD from the New Balance Foundation Obesity Prevention Center at Boston Children’s Hospital and Harvard Medical School. In response to the recent widely publicized observations of decreasing life expectancy among US counties in the Southeast and Midwest, Ludwig raises the hypothesis that technologic advances may no longer be sufficient to compensate for the adverse health effects of obesity.

He goes on to state, “Direct medical costs associated with obesity among noninstitutionalized adults have been estimated to have reached $190 billion annually in 2005, an amount that does not include losses from lower worker productivity.”

What does this have to do with driving the 495 (Mapquest) miles from Hulbert Lake to the Cleveland Clinic? Everything! With the exception of the very sparsely populated areas in northern Michigan, the trip is a visual festival of high-caloric density food. The woods and fields of the rural Midwest are blotted out by billboards for McDonald’s, Wendy’s, Kentucky Fried and scores of local places like Cops and Donuts (Clare, MI). And the drive thru lanes and parking lots for these places are packed. This observation prompted the following chain of thought.

First, I have read, learned, and written a lot about drug costs and their relationship to overall health care costs. Second, JAMA now publishes an expert from Harvard who tells us that the medical cost of obesity passed $190 billion a year a decade ago! Third, new data suggest that dietary composition may have an impact above and beyond caloric balance alone. Fourth, the fast-food industry is not about production and consumption of “high-quality proteins, fruits and vegetables, legumes, nuts, and other whole foods,” as a basic diet.

Where does this leave me? I cannot avoid the growing suspicion that some large players in the food industry are making profits by making us unhealthy, and driving the overall cost of health care up in the process. This seems at least an order of magnitude more villainous than making profits for discovering and developing new drugs to make us healthier.

One of the core values of writing the Packet was to use data to gain perspective on problems. Over the summer months, I’ll look for more data and a clearer perspective on these and other epidemiologic questions.

The Theranos evidence, waiting for a story

WFM
WFM – Undercover investigative reporter

Spoiler alert! If you already believe that you can learn more by analyzing failure than by admiring success, you can skip the rest of the post.

Because I decided to apply to medical school late in my junior year at college, in the summer of 1963, I took organic chemistry as a summer school course at Penn. I was also rowing with my life-long friend, Bernie Witholt, in a double scull at Vesper Boat Club. When the chemistry course ended, in order to keep up the rowing I needed a job and a place to live. Those very basic needs drove me to wandering through the labs in the basement of Penn’s medical school, looking for a temporary job as a lab assistant. Dr. Rita Wetton, an academic pediatrician working on hyaline membrane disease, had just said “good-bye” to her two summer assistants, and she hired me on the spot.

The next morning, I showed up in the lab, put on a white coat, and headed down Hamilton Walk to a small gate in the wall that separated the medical school from the vast grounds of the Philadelphia General Hospital. Going through, the PGH autopsy building was on my right, a non-descript squat stone outbuilding. I was there to collect fresh human lung specimens for the lab.

The dieners (autopsy assistants) seemed totally unsurprised that a college kid in a sport shirt with a white coat over it had wandered in to pick up some lungs. (At the time, I didn’t know that Dr. Wetton had a formal research agreement with the PGH pathology department.) I think they knew that they had a critical, if very basic, role in medical education. They asked if I wanted to stay and watch the autopsy that would yield the specimens. I did. So the process of looking objectively for the clues to what went wrong literally started on my very first day at medical school, months before the acceptance letter came.

As I write this, my desk is a mess. For a couple of weeks, I’ve been holding on to interesting material from the media in the hope that if I look at it carefully, objectively, maybe I can understand what happened to Theranos, the lab testing company that just a couple of years ago achieved a “value” of some $9 billion. How did Elizabeth Holmes, a Stanford drop-out with no formal medical credentials, build a corporate house of cards that is now slowly crashing under financial and regulatory scrutiny? David Crow, writing in The Financial Times magazine on April 18th, presented the facts in a very thoroughly researched article. But looking at the facts is like looking at individual organs at an autopsy, after the diener has washed them, weighed them, and put them in clean pans. What we need now is the pathologist to come in, and with knowledge and experience, he or she will tell the story that puts the facts together into a coherent narrative. At some point, the narrative may well make an instructive case study.

For now, here are just a few thoughts. A laboratory, any lab, is an attempt to reduce what information theory calls “noise.” A clinical study is a the concept of a lab built out to work in the real world. The idea of the lab is to eliminate or control variables. These can include changes in temperature, humidity, light, seismic vibration (read Black Hole Blues!), or by using inclusion/exclusion criteria and randomization, differences between groups of patients, whatever is on your list. In any lab work, reproducibility of results and documentation of methods is absolutely critical. Even so, experiments will fail; things will go wrong. That’s often when you learn that a week in the library is worth a month in the lab. It’s a painful lesson.

With her extraordinary intelligence and charm, Elizabeth Holmes seems to have believed that reproducibility and transparent documentation of methods, the fundamental steps common to both laboratory and clinical research, could be finessed. The Greeks gave that error a name; they called it hubris.

Those principles have tripped up John Darsee, William Summerlin, and many others.     But at the Theranos scale, the error has gone beyond the personal. Board members have sustained tarnished credibility, and financial supporters have lost substantial sums. And behind it all is a sad story; they didn’t do their homework. They didn’t ask to see the nuts and bolts,to subject the data to critical peer review.

The Theranos story is far from over, but it holds important lessons for all of us. We should continue to follow it closely.