Mission and Purpose

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Medicine Across Space and Time is a search for true principles of health and wellness that have persisted over time and across cultures to provide context and answers to the myriad chronic health issues we face today.

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Dr Charles Burwell, cardiologist and Dean of Harvard Medical School from 1935-1949, once famously told an incoming class that “half of what we are going to teach you is wrong, and half is right. Our problem is we don’t know which half is which.”

Being only half wrong may be generous.

One place to start figuring out which half is which, though, is with the idea of the Lindy Effect. This theory states that the longer an idea has been around, the longer it’s likely to continue to be around. The keys to health and wellness that have persisted for the last hundred years will probably be true over the next hundred years. In that same vein, those ideas that have been adopted across cultures are more likely to have value and staying power.  Be wary of fantastic new findings that seem to overturn generational wisdom.

Modern medicine has made major advances in treating acute conditions, like illness from infectious disease and traumatic injuries. It has struggled with chronic conditions such as obesity, heart disease, diabetes, cancer, depression, and dementia. The prevalence of many of these diseases is increasing.

These conditions develop over many years to decades and have innumerable interconnected variables affecting their progression. Their complexity is such that study through traditional scientific processes is insufficient. Experiments that are insufficient in duration or focus on only one variable without properly accounting for confounders are just as likely to produce a harmful result as a helpful one. As systems increase in complexity, bottom-up iterative knowledge tends to outperform top-down authoritative knowledge.

When it comes to health and wellness, this bottom-up knowledge is embedded in the cultural practices that have persisted through generations. This knowledge is often so subtly ingrained in societal norms that its importance is overlooked and quickly disregarded in favor of exciting new findings.

Medicine Across Space and Time is a search for true principles of health and wellness. Truth is a knowledge of things as they were and as they are. True principles persist over time and are adopted across cultures and multiple domains. Understanding health and disease from first principles and in broad context helps us better apply them to the unique health issues we face today and will face in the future.

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Full Essay

Dr Charles Burwell, cardiologist and Dean of Harvard Medical School from 1935-1949, once famously told an incoming class that “half of what we are going to teach you is wrong, and half is right. Our problem is we don’t know which half is which.”

Being only half wrong might be generous.

Even if we give medicine the benefit of the doubt, it often takes decades to sort through and separate the correct information from the incorrect, and sometimes the harmful recommendations persist due to profit-based incentives, political bias, or cultural influence.

It shouldn’t be difficult to find straightforward information about the best ways to live a long and active life. It’s a universal desire, but diving into the massive amounts of available data often leaves one feeling confused and frustrated. The space is filled with both the well-intentioned and the grifters.

Guidelines from governmental agencies and consensus statements from medical associations in consult with your personal physician are a good place to start. It’s reasonable, though, to be concerned about corporate dollars insidiously influencing public policy. And as anyone who has watched the sausage get made knows, consensus statements don’t have near the support and agreement that the final product conveys. Asking any one of the involved “experts” their personal opinion would result in different advice than what’s written. And it is impossible to have a thorough conversation on such a broad and wide-ranging topic with your doctor in the 7-10 minutes they have to spend with you.

Less official information channels can also have significant value. Whether it’s in a book, an article (in or out of a scientific journal), or social media, there are plenty of knowledgeable people sharing their thoughts on health. Quality varies wildly, both positively and negatively.

Although Dr. Burwell was probably being humbly hyperbolic, if a highly curated medical school curriculum is only half right, imagine the accuracy of the troves of publicly available information!

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But why is it so hard? Why don’t we have definitive answers on preventing heart disease, curing diabetes, and healing major depressive disorder? Why is there so much variance and conflicting information?

Significant progress in many areas of medicine has been made since Dr. Burwell’s statement. Capital M Medicine (as in the institution as a whole) has done well in raising the average lifespan by treating acute trauma and illnesses that have historically lowered the mean age of death. It has struggled, though, in the fight against chronic diseases, such as metabolic syndrome (obesity, diabetes, hypertension, etc.), dementia, cancer, and mental illness.

Chronic disease is, by definition, a disease that develops and persists for an extended amount of time. It doesn’t pop up overnight, and it can’t be cured overnight. It often percolates under the surface without detection for years before any symptoms appear. These are the types of problems modern medicine has struggled with.

These are wickedly difficult problems to solve due to the immense complexity of the disease process. There are innumerable and unmeasurable factors with undetermined influence throughout this process and affect individuals based not only on genetics, but epigenetics as well. (Epigenetics are factors that influence expression of genes encoded in DNA but are not part of the DNA itself.)

Proving causation is the holy grail of clinical studies. In a scientific study with the goal of proving causality (clinical trial), one independent variable is changed, and an outcome is measured. If the outcome is significantly different, then it’s reasonable to say the thing you changed caused it. Significance, in this sense, is statistical, which means there has been enough trials or participants that the outcome is unlikely to be due to chance alone. It does not mean the desired outcome happened every time.

In physics, hypotheses can be confirmed and proven over and over again. In chemistry, this happens most of the time. In biology, with all its inherent complexity, findings often barely meet the minimum standard for statistical significance and can be very difficult to reproduce in subsequent studies. When you hear the term biology is “squishy”, it doesn’t mean you can poke the things you’re studying. It means biology is complex, variable, and unpredictable.

A 2005 study titled “Why Most Published Research Findings are False” suggests that over half of published findings might be exaggerated or blatantly false due to deficiencies in study design, multiple comparisons, “p-hacking” (statistical manipulation to produce the desired response), or the pursuit of novel, rather than confirmatory findings. To get published, a study must show something new and cool; it can’t just confirm what is already known. It would also be terrible to spend tens (or hundreds) of thousands of dollars of grant money and years of study only to find that the desired outcome barely missed the threshold of significance. There is obvious incentive to maybe just play around with the data a little bit, but definitely not in a bad way, to make it show a statistically significant result. There are lies, damned lies, and statistics. A 2015 experiment attempted to replicated 100 psychological studies and found that only about 36% of the replications yielded significant results. When it comes to medical research, psychology is the squishiest of the squishy, but the low reproducibility of the findings is still concerning.

Another difficulty in studying chronic disease is the length of time necessary to track the development and progression of a disease. The Bogalusa Heart Study performed autopsies on young people ranging from ages 2-39 that died from traumatic causes (accidents, murders, suicides) and surprisingly found fatty streaks in coronary arteries, an early sign of heart disease, in many of the children. When it comes to heart disease, fatty streaks develop into fibrous plaques, which can then increase in size, impairing blood flow through the coronary arteries (the arteries the supply blood to the heart muscle itself). Decreased blood flow can result in chest pain with activity (or at rest, if it’s bad enough), when the heart muscle needs more blood to meet energy demands and make heart attacks more likely.

The point here is that the first signs of heart disease were found in children, but these were hidden except via autopsy, and symptoms likely wouldn’t show up until middle age at the earliest. How then can the disease course truly be studied?

Studying diseases with undetectable beginnings that take decades to develop is near impossible. Longitudinal studies are attempts to follow the same group of people over many years to study disease progression. Aside from the time required often exceeding the career length of the investigators, these studies are also expensive, have high rates of participant drop out, and have innumerable confounders. Artificial end points or time periods are sometimes used to make the studies more manageable. Examples include measuring bone mineral density when study osteoporosis rather than the actual endpoint of interest, which is a bone fracture. Another example is measuring change in glycated hemoglobin, or A1c, when studying diabetes, rather than waiting for the development of kidney disease, peripheral nerve disease, or death.

When using these surrogate end points, the risk of developing the true endpoint can usually be inferred, but it leaves significant room for error. In studies for cancer treatment, change in tumor size is often used as an artificial endpoint in order to get cancer drugs approved more quickly (which for the most part is a noble goal). The problem is, though, that there is often correlation between change in tumor size and prolonged survival, the true important end point. Avastin for metastatic breast cancer was approved by the FDA in 2008 because of its rapid effect on tumor size, but the indication for its use was removed in 2011 when further studies showed it did not contribute to extended or improved lifespan.

In addition to using artificial endpoints as surrogates for the true endpoints, sometimes arbitrary time periods, rather than outcomes, are used. New medications generally go through pre-clinical and then 3 phases of drug testing, with each successive step including more people. If approved, “Phase 4” is continued surveillance after the drug is widely available. It is expected that some side effects will emerge in this phase, but the hope is that the risks for serious negative outcomes have been identified and mitigated in the earlier trials. A study must end at some point.

In the 1980s, observational studies showed that hormone replacement therapy (HRT) reduced the risk of heart disease in post-menopausal women. HRT was then widely recommended on this basis. When the results of the much longer Women’s Health Initiative were released in 2002, though, it showed that HRT actually increased risk of breast cancer and heart disease. The study focusing on HRT with estrogen and progestin replacement was stopped early after about 5 years because of the 26% increased relative risk of invasive breast cancer and 29% increased risk of heart attack. This equates to 8 and 9 extra women respectively out of 10,000 suffering from the negative side effect, but these are not minor side effects. Since this number is fairly small, it is also why HRT is still often used to help with moderate to severe symptoms of menopause but is no longer widely recommended.

The most egregious example of drawing conclusions from too short of a time frame were the initial claims that slow-release opioid medications like OxyContin were not addictive. This assertion was initially based on a 1980 letter published in the New England Journal of Medicine that patients given slow-release pain medication over 5 or less days in a hospital setting had very low rates of addiction. It’s difficult to overstate the monumental negative outcomes of such a short-sighted conclusion. It’s less difficult to understand how corporate greed and inept regulatory oversight led to the opioid crisis. But even with a claim so obviously false, prescriptions for the drug increased year over year from 1995 to 2010.

In contrast to the OxyContin example, the Framingham Heart Study is one of the most renowned and longest-running epidemiological studies in medical history. It was initiated in 1948 by the National Heart Institute to identify the common factors or characteristics that contribute to cardiovascular disease. The study initially enrolled over 5,000 men to follow throughout their lives to determine what factors might contribute to the risk of heart disease. The trial has since enrolled second and third generation participants and continues today. The wealth of data generated by this study (it pioneered the idea of identifying “risk factors”) has contributed enormously to the current understanding of cardiovascular disease.

Despite its valiant effort, this study faces the same challenges that any epidemiological study faces. An epidemiological study, unlike other types of research studies that might focus on individual-level factors or lab-based experiments, analyzes larger population-level data to uncover trends, risk factors, and outcomes over time. It seeks to understand the patterns, causes, and effects of health and disease conditions in specific populations.

Drawing meaningful conclusions from epidemiological studies can be challenging because they rely on observational data, which can show associations, but cannot prove cause and effect. They can be influenced by many confounding factors, such as lifestyle or genetic differences that are difficult (impossible) to control for. But there is no practical way to study chronic disease other than longitudinal epidemiological studies, and we are left wanting any hard scientific evidence. To quote Nietzsche, “causes are fictions we ourselves invent”.

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The scientific process is insufficient to properly study chronic disease. It is too complicated and interconnected. This may sound heretical, but it is impossible to sufficiently control and measure all the contributing factors over a long enough period of time to draw significant conclusions. Each variable involved in the disease process is so intertwined with others that trying too hard to isolate it is just as likely to produce a misleading outcome as a true one.

Evidence-informed recommendations are the best we can hope for, which leaves room for a lot of ambiguity in ensuing recommendations. Unfortunately, official recommendations generally give the impression that the science is settled and there should be no further arguments against the edicts handed down from governing medical bodies. And this is before so many powerful competing corporate and political influences undoubtedly try to put their hand on the scale.

This doesn’t mean disregard science. Important advancements have been made in the treatment of chronic diseases due to diligent research efforts. It means understand the complexity and variability and take recommendations with a grain of salt. It means not all that glitters is gold, and the newest hot research finding or medication may not be all it’s made out to be. For anyone who has watched the sausage being made, consensus statements and recommendations from medical associations are generally a collection of compromises that don’t have near the strength and support the final product conveys.

So where does that leave us in the search for how to live a long and healthy life? Are we at the mercy of biohackers or gym bros on social media, or the medical organizations and journals that subsist solely on donations from large corporations?

Humans have actually really flourished as a species for centuries, even before modern medical breakthroughs. Childhood diseases, bacteria, and accidents took too many people too early, and modern interventions have helped save a lot of those people. In many ways, though, Americans (and much of the world population) is unhealthier than it’s ever been. Obesity, diabetes, depression, many cancers, and dementia (and others) are all increasing, worsening quality of life and raising both individual and collective healthcare expenditures.

Medicine Across Space and Time is a search for true principles of health and wellness. Truth is a knowledge of things as they are and as they were.

The Lindy Effect, made popular by Nassim Nicholas Taleb, states that future life expectancy of an idea or technology is proportional to its current age. More simply put, the longer something has been around, the longer it’s likely to continue to be around. In that same vein, those ideas that have been adopted across cultures are more likely to have value and staying power. Be very wary of “new findings” that miraculously invalidate widespread generational practices.

To help answer Dr. Burwell’s question and determine which half of medical knowledge currently being taught is correct, start with what has been taught the longest. The keys to health and longevity that have been known for one hundred years will probably be the keys to health and longevity over the next hundred years. The ideas developed over the last one to two decades may be helpful, but the chances are far lower. (Think of the major shift in dietary recommendations in America in the 1970s compared to the typical diet of the preceding 100 years and the obesity epidemic that almost immediately followed.) This is especially important when it comes to overall health and vitality, as these concepts can be difficult to quantify and investigate with scientific rigor.

There are other ways to develop and progress societal knowledge other than formal research studies. There is much to be learned from the health practices that are imbedded in cultural traditions. This isn’t necessarily explicit knowledge packaged neatly with an abstract, methodology, discussion, and conclusion. It’s implicitly passed from generation to generation to help ensure continuing success. It’s so subtly imbedded in everyday life, it’s easy to disregard. It has stood the test of time and consistently produced results.

In contrast to institutional research studies, cultural norms around health develop from the bottom up, rather from the top down. There’s no central director dictating the exercise and dietary choices of the individuals. The habits developed are emergent properties of a population that gradually proved to produce the healthiest individuals and were thus adopted by others in the group. Their persistence helps diminish the effects of confounders and randomness just through the unyielding filter of time. It doesn’t have the appeal of authoritative declaration, but it has the significance of producing robust positive outcomes. And while authors of research studies may have the incentive to massage their study outcomes to produce publishable results, the inherent cultural knowledge has no other motive than to encourage survival of the species.

There is a sweet spot in taking the knowledge passed down over centuries that has helped humanity thrive, while also incorporating new medical knowledge. Modern technology has greatly increased our knowledge of how things are, often down to the most minute cellular detail. New discoveries can theoretically invalidate previous knowledge, but more often than not, they simply add context. For example, it is extremely unlikely that any new knowledge about the intricacies of lipid metabolism or atherogenesis will invalidate ancestral diets that have persisted for centuries. True principles persist over time and are adopted across cultures and multiple domains. Understanding these principles of health in a broader context helps us better apply them to the unique health issues we face today.

By embracing multi-generational health practices, we are relying on the longest, most robust longitudinal epidemiologic studies available. Any study that seemingly overturns decades of acquired wisdom should be bulletproof. The burden of evidence is far greater on the new information than it is on the old.

In the 1977 “Dietary Goals for the United States”, which famously condemns animal-based products and recommends a monumental nationwide dietary shift to grains, Dr. D.M. Hegsted, another Harvard physician and the driving influential force in the new guidelines, writes that “the diet we eat today was not planned or developed for any particular purpose…The question to be asked, therefore, is not why should we change our diet, but why not?”

This statement is first and foremost an excellent example the overwhelming rise in hubris in medicine in the 30 years between Dr. Burwell and Dr. Hegsted. Unfortunately, medicine has continued this trajectory over the last 50 years. “The Science” of medicine has become an unassailable monolith where dictates are handed down from on high to be unquestionably followed. (If further evidence is needed on this point, read almost anything Anthony Fauci has said over since 2020.) The recent efforts to label anyone questioning official health guidelines as a radicalized conspiracy theorist is reminiscent of medieval Catholic church practices.

Secondly, the fundamental basis and logic of Dr. Hegel’s statement is categorically false. The standard American diet at that time was developed over decades solely for the purpose of the flourishing and survival of the human species. True, it wasn’t authoritatively directed by an omnipotent governmental organization, but rather by assimilating best practices. The question should always be “Why should we deviate from generational knowledge unless we have a really, really, really good reason to do so.” Not “Why not?”. It was not long after these new 1977 guidelines that obesity and overall rates of chronic disease began to skyrocket.

Adhering to cultural practices of health and wellness is not a reductionist view clung to by Luddites unable to comprehend the magical brilliance of modern medicine. It is rather accepting that the primary factors of health -- specifically diet, exercise, sleep, and mental health-- are extremely complex and are resistant to the study of individual variables over arbitrary timelines. Yes, medical knowledge has grown substantially, and our natural inclination is that new knowledge should lead to intervention. This is not always true, especially when all the ancillary effects cannot be fully accounted for. New medical developments often help treat or manipulate diseases that are a result of straying from the robust existing knowledge in the first place.

Medicine Across Space and Time is a study of health from first principles and how this knowledge has progressed over time. Medical guidelines will always have inherent uncertainty, whether this is openly portrayed or not. Given the ambiguity, understanding the issues in as broad of context as possible is imperative. Best practices, or the “right” answer, is most likely the one that has been preserved over generations and adopted across cultures.

The focus is not only on curing the disease (the negative side of health), but also strengthening good health habits (the positive side) to preserve health and prevent disease. The pillars of health include diet, exercise, sleep, and mood (mental health). Focusing on strengthening these pillars, rather than treating disease symptoms of an illness, is the more productive focus and one area where the current paradigm of modern medicine falls short. Since these pillars are the keys to health, longevity, and survival of the species, the keys to strengthening them are embedded into cultural practices passed down through generations. Observing how the practices relating to these pillars developed, evolved, and propagated is supremely useful.

Modern life, of course, brings challenges with it that previous generations didn’t face, such as the wanton availability of calorically dense food, sedentary lifestyles, and the constant stressors of social media. Modern medical advances can be helpful, but even more helpful is understanding and applying ancient principles to the new challenges. Long-held practices around cultural staples such as diet, exercise, and socialization are often disregarded because they are thought to have developed only out of necessity, but now that there are other options, these practices can be forgotten. This is a dangerous presumption.

Most of the major health issues we face today are not new, even though it may seem that way given their rise in prevalence. Understanding these issues and their solutions in the broadest context possible is imperative. What has changed to lead to skyrocketing levels of chronic disease and why is it so hard to treat? What healthy practices have stood the test of time and been adopted across cultures? How can the insidious influence of corporate and political bias be weeded out? Answers to these questions can help you make the right health decisions for you and your family, and this is the goal of Medicine Across Space and Time.

References

1.     Sugar Industry and Coronary Heart Disease Research: A Historical Analysis of Internal Industry Documents; JAMA, 2016

2.     Is There a Correlation between Dietary and Blood Cholesterol? Evidence from

Epidemiological Data and Clinical Interventions; NIH, 2023

3.     Statin Safety and Associated Adverse Events: A Scientific Statement from the American Heart Association

4.     William Castelli, Concerning the Possibility of a Nut, Archives of Internal Medicine, 1992

5.     Minnesota Coronary Experiment