Who Qualifies as an “Expert” And How Can We Decide Who Is Trustworthy?
This article is part of the magazine, "The Future of Science In America: The Election Issue," co-published by LeapsMag, the Aspen Institute Science & Society Program, and GOOD.
Expertise is a slippery concept. Who has it, who claims it, and who attributes or yields it to whom is a culturally specific, sociological process. During the COVID-19 pandemic, we have witnessed a remarkable emergence of legitimate and not-so-legitimate scientists publicly claiming or being attributed to have academic expertise in precisely my field: infectious disease epidemiology. From any vantage point, it is clear that charlatans abound out there, garnering TV coverage and hundreds of thousands of Twitter followers based on loud opinions despite flimsy credentials. What is more interesting as an insider is the gradient of expertise beyond these obvious fakers.
A person's expertise is not a fixed attribute; it is a hierarchical trait defined relative to others. Despite my protestations, I am the go-to expert on every aspect of the pandemic to my family. To a reporter, I might do my best to answer a question about the immune response to SARS-CoV-2, noting that I'm not an immunologist. Among other academic scientists, my expertise is more well-defined as a subfield of epidemiology, and within that as a particular area within infectious disease epidemiology. There's a fractal quality to it; as you zoom in on a particular subject, a differentiation of expertise emerges among scientists who, from farther out, appear to be interchangeable.
We all have our scientific domain and are less knowledgeable outside it, of course, and we are often asked to comment on a broad range of topics. But many scientists without a track record in the field have become favorites among university administrators, senior faculty in unrelated fields, policymakers, and science journalists, using institutional prestige or social connections to promote themselves. This phenomenon leads to a distorted representation of science—and of academic scientists—in the public realm.
Trustworthy experts will direct you to others in their field who know more about particular topics, and will tend to be honest about what is and what isn't "in their lane."
Predictably, white male voices have been disproportionately amplified, and men are certainly over-represented in the category of those who use their connections to inappropriately claim expertise. Generally speaking, we are missing women, racial minorities, and global perspectives. This is not only important because it misrepresents who scientists are and reinforces outdated stereotypes that place white men in the Global North at the top of a credibility hierarchy. It also matters because it can promote bad science, and it passes over scientists who can lend nuance to the scientific discourse and give global perspectives on this quintessentially global crisis.
Also at work, in my opinion, are two biases within academia: the conflation of institutional prestige with individual expertise, and the bizarre hierarchy among scientists that attributes greater credibility to those in quantitative fields like physics. Regardless of mathematical expertise or institutional affiliation, lack of experience working with epidemiological data can lead to over-confidence in the deceptively simple mathematical models that we use to understand epidemics, as well as the inappropriate use of uncertain data to inform them. Prominent and vocal scientists from different quantitative fields have misapplied the methods of infectious disease epidemiology during the COVID-19 pandemic so far, creating enormous confusion among policymakers and the public. Early forecasts that predicted the epidemic would be over by now, for example, led to a sense that epidemiological models were all unreliable.
Meanwhile, legitimate scientific uncertainties and differences of opinion, as well as fundamentally different epidemic dynamics arising in diverse global contexts and in different demographic groups, appear in the press as an indistinguishable part of this general chaos. This leads many people to question whether the field has anything worthwhile to contribute, and muddies the facts about COVID-19 policies for reducing transmission that most experts agree on, like wearing masks and avoiding large indoor gatherings.
So how do we distinguish an expert from a charlatan? I believe a willingness to say "I don't know" and to openly describe uncertainties, nuances, and limitations of science are all good signs. Thoughtful engagement with questions and new ideas is also an indication of expertise, as opposed to arrogant bluster or a bullish insistence on a particular policy strategy regardless of context (which is almost always an attempt to hide a lack of depth of understanding). Trustworthy experts will direct you to others in their field who know more about particular topics, and will tend to be honest about what is and what isn't "in their lane." For example, some expertise is quite specific to a given subfield: epidemiologists who study non-infectious conditions or nutrition, for example, use different methods from those of infectious disease experts, because they generally don't need to account for the exponential growth that is inherent to a contagion process.
Academic scientists have a specific, technical contribution to make in containing the COVID-19 pandemic and in communicating research findings as they emerge. But the liminal space between scientists and the public is subject to the same undercurrents of sexism, racism, and opportunism that society and the academy have always suffered from. Although none of the proxies for expertise described above are fool-proof, they are at least indicative of integrity and humility—two traits the world is in dire need of at this moment in history.
[Editor's Note: To read other articles in this special magazine issue, visit the beautifully designed e-reader version.]
Scientists Just Started Testing a New Class of Drugs to Slow--and Even Reverse--Aging
Imagine reversing the processes of aging. It's an age-old quest, and now a study from the Mayo Clinic may be the first ray of light in the dawn of that new era.
The immune system can handle a certain amount of senescence, but that capacity declines with age.
The small preliminary report, just nine patients, primarily looked at the safety and tolerability of the compounds used. But it also showed that a new class of small molecules called senolytics, which has proven to reverse markers of aging in animal studies, can work in humans.
Aging is a relentless assault of chronic diseases including Alzheimer's, cardiovascular disease, diabetes, and frailty. Developing one chronic condition strongly predicts the rapid onset of another. They pile on top of each other and impede the body's ability to respond to the next challenge.
"Potentially, by targeting fundamental aging processes, it may be possible to delay or prevent or alleviate multiple age-related conditions and many diseases as a group, instead of one at a time," says James Kirkland, the Mayo Clinic physician who led the study and is a top researcher in the growing field of geroscience, the biology of aging.
Getting Rid of "Zombie" Cells
One element common to many of the diseases is senescence, a kind of limbo or zombie-like state where cells no longer divide or perform many regular functions, but they don't die. Senescence is thought to be beneficial in that it inhibits the cancerous proliferation of cells. But in aging, the senescent cells still produce molecules that create inflammation both locally and throughout the body. It is a cycle that feeds upon itself, slowly ratcheting down normal body function and health.
Disease and harmful stimuli like radiation to treat cancer can also generate senescence, which is why young cancer patients seem to experience earlier and more rapid aging. The immune system can handle a certain amount of senescence, but that capacity declines with age. There also appears to be a threshold effect, a tipping point where senescence becomes a dominant factor in aging.
Kirkland's team used an artificial intelligence approach called machine learning to look for cell signaling networks that keep senescent cells from dying. To date, researchers have identified at least eight such signaling networks, some of which seem to be unique to a particular type of cell or tissue, but others are shared or overlap.
Then a computer search identified molecules known to disrupt these signaling pathways "and allow cells that are fully senescent to kill themselves," he explains. The process is a bit like looking for the right weapons in a video game to wipe out lingering zombie cells. But instead of swords, guns, and grenades, the list of biological tools so far includes experimental molecules, approved drugs, and natural supplements.
Treatment
"We found early on that targeting single components of those networks will only kill a very small minority of senescent cells or senescent cell types," says Kirkland. "So instead of going after one drug-one target-one disease, we're going after networks with combinations of drugs or drugs that have multiple targets. And we're going after every age-related disease."
The FDA is grappling with guidance for researchers wanting to conduct clinical trials on something as broad as aging rather than a single disease.
The large number of potential senolytic (i.e. zombie-neutralizing) compounds they identified allowed Kirkland to be choosy, "purposefully selecting drugs where the side effects profile was good...and with short elimination half-lives." The hit and run approach meant they didn't have to worry about maintaining a steady state of drugs in the body for an extended period of time. Some of the compounds they selected need only a half hour exposure to trigger the dying process in senescent cells, which can then take several days.
Work in mice has already shown impressive results in reversing diabetes, weight gain, Alzheimer's, cardiovascular disease and other conditions using senolytic agents.
That led to Kirkland's pilot study in humans with diabetes-related kidney disease using a three-day regimen of dasatinib, a kinase inhibitor first approved in 2006 to treat some forms of blood cancer, and quercetin, a flavonoid found in many plants and sold as a food supplement.
The combination was safe and well tolerated; it reduced the number of senescent cells in the belly fat of patients and restored their normal function, according to results published in September in the journal EBioMedicine. This preliminary paper was based on 9 patients in an ongoing study of 30 patients.
Kirkland cautions that these are initial and incomplete findings looking primarily at safety issues, not effectiveness. There is still much to be learned about the use of senolytics, starting with proof that they actually provide clinical benefit, and against what chronic conditions. The drug combinations, doses, duration, and frequency, not to mention potential risks all must be worked out. Additional studies of other diseases are being developed.
What's Next
Ron Kohanski, a senior administrator at the NIH National Institute on Aging (NIA), says the field of senolytics is so new that there isn't even a consensus on how to identify a senescent cell, and the FDA is grappling with guidance for researchers wanting to conduct clinical trials on something as broad as aging rather than a single disease.
Intellectual property concerns may temper the pharmaceutical industry's interest in developing senolytics to treat chronic diseases of aging. It looks like many mix-and-match combinations are possible, and many of the potential molecules identified so far are found in nature or are drugs whose patents have or will soon expire. So the ability to set high prices for such future drugs, and hence the willingness to spend money on expensive clinical trials, may be limited.
Still, Kohanski believes the field can move forward quickly because it often will include products that are already widely used and have a known safety profile. And approaches like Kirkland's hit and run strategy will minimize potential exposure and risk.
He says the NIA is going to support a number of clinical trials using these new approaches. Pharmaceutical companies may feel that they can develop a unique part of a senolytic combination regimen that will justify their investment. And if they don't, countries with socialized medicine may take the lead in supporting such research with the goal of reducing the costs of treating aging patients.
A New Test Aims to Objectively Measure Pain. It Could Help Legitimate Sufferers Access the Meds They Need.
"That throbbing you feel for the first minute after a door slams on your finger."
This is how Central Florida resident Bridgett Willkie describes the attacks of pain caused by her sickle cell anemia – a genetic blood disorder in which a patient's red blood cells become shaped like sickles and get stuck in blood vessels, thereby obstructing the flow of blood and oxygen.
"I found myself being labeled as an addict and I never was."
Willkie's lifelong battle with the condition has led to avascular necrosis in both of her shoulders, hips, knees and ankles. This means that her bone tissue is dying due to insufficient blood supply (sickle cell anemia is among the medical conditions that can decrease blood flow to one's bones).
"That adds to the pain significantly," she says. "Every time my heart beats, it hurts. And the pain moves. It follows the path of circulation. I liken it to a traffic jam in my veins."
For more than a decade, she received prescriptions for Oxycontin. Then, four years ago, her hematologist – who had been her doctor for 18 years – suffered a fatal heart attack. She says her longtime doctor's replacement lacked experience treating sickle cell patients and was uncomfortable writing her a prescription for opioids. What's more, this new doctor wanted to place her in a drug rehab facility.
"Because I refused to go, he stopped writing my scripts," she says. The ensuing three months were spent at home, detoxing. She describes the pain as unbearable. "Sometimes I just wanted to die."
One of the effects of the opioid epidemic is that many legitimate pain patients have seen their opioids significantly reduced or downright discontinued because of their doctors' fears of over-prescribing addictive medications.
"I found myself being labeled as an addict and I never was...Being treated like a drug-seeking patient is degrading and humiliating," says Willkie, who adds that when she is at the hospital, "it's exhausting arguing with the doctors...You dread them making their rounds because every day they come in talking about weaning you off your meds."
Situations such as these are fraught with tension between patients and doctors, who must remain wary about the risk of over-prescribing powerful and addictive medications. Adding to the complexity is that it can be very difficult to reliably assess a patient's level of physical pain.
However, this difficulty may soon decline, as Indiana University School of Medicine researchers, led by Dr. Alexander B. Niculescu, have reportedly devised a way to objectively assess physical pain by analyzing biomarkers in a patient's blood sample. The results of a study involving more than 300 participants were published earlier this year in the journal Molecular Psychiatry.
Niculescu – who is both a professor of psychiatry and medical neuroscience at the IU School of Medicine – explains that, when someone is in severe physical pain, a blood sample will show biomarkers related to intracellular adhesion and cell-signaling mechanisms. He adds that some of these biomarkers "have prior convergent evidence from animal or human studies for involvement in pain."
Aside from reliably measuring pain severity, Niculescu says blood biomarkers can measure the degree of one's response to treatment and also assess the risk of future recurrences of pain. He believes this new method's greatest benefit, however, might be the ability to identify a number of non-opioid medications that a particular patient is likely to respond to, based on his or her biomarker profile.
Clearly, such a method could be a gamechanger for pain patients and the professionals who treat them. As of yet, health workers have been forced to make crucial decisions based on their clinical impressions of patients; such impressions are invariably subjective. A method that enables people to prove the extent of their pain could remove the stigma that many legitimate pain patients face when seeking to obtain their needed medicine. It would also improve their chances of receiving sufficient treatment.
Niculescu says it's "theoretically possible" that there are some conditions which, despite being severe, might not reveal themselves through his testing method. But he also says that, "even if the same molecular markers that are involved in the pain process are not reflected in the blood, there are other indirect markers that should reflect the distress."
Niculescu expects his testing method will be available to the medical community at large within one to three years.
Willkie says she would welcome a reliable pain assessment method. Well-aware that she is not alone in her plight, she has more than 500 Facebook friends with sickle cell disease, and she says that "all of their opioid meds have been restricted or cut" as a result of the opioid crisis. Some now feel compelled to find their opioids "on the streets." She says she personally has never obtained opioids this way. Instead, she relies on marijuana to mitigate her pain.
Niculescu expects his testing method will be available to the medical community at large within one to three years: "It takes a while for things to translate from a lab setting to a commercial testing arena."
In the meantime, for Willkie and other patients, "we have to convince doctors and nurses that we're in pain."