Over the years, many people suffering from certain debilitating diseases and conditions have faced skepticism, judgment and ostracism.
Their situation is portrayed as arising from their own moral failings or lack of willpower, or as psychosomatic, without a physical cause. And because of the skepticism and judgment, they have often faced clinical indifference, with relatively little funding going toward research into what is happening to them. Now progress is being made and research is identifying the biological causes and genetic risk factors for many such diseases and conditions. And, although much work remains to be done, The Jackson Laboratory is at the forefront of these efforts to improve the lives of the millions of people affected.
1. Addiction and substance use disorders
The stigmas associated with addiction have had particularly tragic consequences in recent years. The opioid crisis has been devastating, with the estimated death toll topping 1 million people to date. But attitudes and policies in the United States are still largely based in the debunked “Just say no,” willpower-dependent school of thought rather than in the reality that addiction is a biological and treatable disease. And even as the death toll mounts, the judgmental attitudes persist, making access to effective recovery medications difficult. Research has now shown conclusively that susceptibility to addiction and risk of overdose are highly variable from person to person, and that genetics play a significant role. Researchers at JAX are working to unravel the complex biological mechanisms of addiction and substance use disorders, which encompass the influences of hundreds and perhaps even thousands of genes. The ultimate goal at JAX is to find molecular targets for treatments that can break the cycle of addiction and substance use and enable recovery.
2. Endometriosis
Medicine has long treated women like they are, on average, slightly smaller men. The National Institutes of Health didn’t even mandate that clinical trials include women until 1993, and the belief that women’s hormonal cycles would skew trial data lasted for decades after. As a result, diseases such as endometriosis, which afflicts millions of women and can cause severe pain and infertility, have received relatively little attention. Endometriosis is caused by proliferating cells that resemble those comprising the endometrial lining of the uterus, which is generated and eliminated as part of the menstrual cycle. For unknown reasons, the cells are present and grow outside of the uterus, such as on the ovaries or in the peritoneum. At long last, however, scientists are delving into the causes and biological details of endometriosis, searching for improvements to the invasive and, at times, ineffective interventions currently available. And JAX is at the forefront of progress for endometriosis research, leading important research studies and successfully lobbying for a biorepository to provide important resources for future research.
3. ME/CFS
Imagine having the flu and never recovering. That terrible feeling is among the symptoms experienced by those with myalgic encephalomyelitis (ME), originally and still commonly known as chronic fatigue syndrome (CFS). The name CFS implies that it’s just a condition of being fatigued, which, in normal cases, is easily resolved with rest and healthy habits. And that’s how physicians have generally approached it — if they didn’t dismiss it outright as psychosomatic — but ME/CFS does not resolve itself. Further exacerbating the situation, the underlying causes of ME/CFS and its symptoms, which can be debilitating, have remained unknown, and there are no biomarkers of disease or effective therapies. Fortunately, though, that situation is changing. Scientists at JAX and elsewhere have found compelling clues in the immune cells of ME/CFS patients that suggest that, somehow, their immune systems are chronically activated following a viral infection instead of shutting down after the acute phase of illness. The findings provide a roadmap for identifying conclusive diagnostic criteria for ME/CFS and insights for developing effective therapies.
4. Long COVID
Fairly early in the COVID-19 pandemic, a pattern emerged that worsened an already dire situation. While most people returned to normal health once they recovered from the initial SARS-CoV-2 infection, a sizable minority did not. They reported lingering brain fog, debilitating fatigue, post-exertional malaise and many other symptoms. At first, many were dismissed by the medical community — the similarities to ME/CFS and its patients were and are notable — but over time it became obvious that post-COVID-19 conditions are very real and can be quite serious. The exact cause(s) of the disease, called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, long COVID, remain(s) unknown. Reactivation of residual viral particles has been implicated, as well as immune dysfunction (similar to that in ME/CFS) and autoimmune activity. To gain more insight, researchers at JAX used pooled clinical data to investigate long COVID based on the characteristics of diagnosed patients. The work identified distinct long COVID subtypes, with important implications for more precisely identifying the underlying causes and for developing effective interventions.
5. Metabolic syndrome
During the 1950s and 1960s, a scientist named Douglas Coleman was hard at work at JAX. He was particularly interested in two mouse strains: ob, which invariably became severely obese and mildly diabetic, and db, which were severely diabetic and less obese. In a series of ingenious experiments that subsequently brought him international acclaim, Coleman proved that there was something circulating in the blood — he called it a “satiety factor” — that suppressed appetite. Dysfunction led to obesity and diabetes, conditions that had long been associated with a lack of willpower or self-control. This discovery of leptin now known to be a key part of a robust system of metabolic checks and balances, showed that for many people genetics overrides behavior in determining their weight and metabolism. The stigma remains, but continued metabolic research in mice has led to the recent development of drugs like Wegovy and Ozempic, both glucagon-like peptide-1 (GLP-1) receptor agonists, as treatments for weight loss, diabetes and cardiovascular disease. These drugs have already revolutionized treatment for metabolic disease, so it will be interesting to see what the future holds.