Month: August 2021

In science, advances are a daily occurrence, but true breakthroughs are rare. What does it take to achieve world-changing scientific breakthroughs? Some are the result of a lucky accident, combined with curiosity: scientists traveling down one road suddenly find reason to veer onto another road, one they never planned to travel — a road that may well lead nowhere.

Other major breakthroughs stem from scientists pursuing a very specific dream. One day, usually early in their career, they get an idea that they can’t stop thinking about. It’s crazy, they say to themselves, but is it really impossible? They talk to respected colleagues who often remind them of all the reasons their idea might not work, and how damaging this could be for their career. It’s a sobering message, yet the idea won’t die. So, they scramble to find financial support and seek out colleagues willing to risk traveling that road with them — a road that may well lead nowhere. But sometimes the road leads to major breakthroughs like penicillin and mRNA vaccines.

Breakthroughs due to lucky accidents and curiosity

One day in 1928, Dr. Alexander Fleming at St. Mary’s Hospital in London was growing bacteria in a laboratory dish. Fleming was not pursuing a scientific dream. He was a microbiologist, just doing his job.

Then he noticed something odd: overnight, another kind of microbe, a fungus, had traveled through the air, landed on the laboratory dish, and started to grow and spread on the dish where the bacteria were growing. Fleming soon noticed that the growing fungus seemed to be killing the bacteria. He surmised that it was making some substance that killed the bacteria. Because the name of the fungus was Penicillium rubens, he called the substance the fungus was making “penicillin.”

When Fleming published a paper about his discovery, few were interested. It took another 10 years before other scientists tried to generate large amounts of penicillin to see if it might be able to cure bacterial infections and save lives. We all know how that worked out.

Fleming’s scientific breakthrough, like some others, occurred not because Fleming had a brilliant idea and exclaimed “Eureka!” Instead, it occurred because he noticed something and said, “That’s odd,” and then tried to figure it out.

Breakthroughs due to persistence and resilience in pursuit of a dream

The story of mRNA vaccines, like the Pfizer/BioNTech and Moderna vaccines for COVID-19, is very different from the story of penicillin. For 30 years, a small group of scientists believed that mRNA vaccines would have great advantages over traditional vaccines — if only several obstacles could be overcome. Many of these scientists gave up as they encountered those obstacles, but a few persisted and, ultimately, succeeded. (I described what mRNA vaccines are, how they work, and how obstacles were overcome in a previous blog post.)

One scientist, Dr. Katalin Karikó, joined the faculty of the University of Pennsylvania in the early 1990s with the dream of creating an mRNA vaccine. She applied for grants to support her work, but was repeatedly rejected: the reviewers stated that it was so unlikely that she or anyone could overcome the obstacles that supporting her research would be a wasted investment. Her university only agreed to continue supporting her work if she accepted a demotion and a pay cut. She accepted both, and doggedly pursued her dream.

One major obstacle to mRNA vaccines particularly fascinated her: the violent reaction of the immune system when it encounters mRNA from a virus. Ten years of dogged work helped Karikó and her colleague Drew Weissman figure out how to make a small change in mRNA that prevented that violent immune response — a major step in making all mRNA vaccines possible. Without this, the world wouldn’t have mRNA COVID vaccines today.

Two other scientists who created the Pfizer/BioNTech COVID vaccine, Uğur Şahin and Őzlem Turëci, are Turkish immigrants to Germany who met, fell in love with the idea of creating an mRNA vaccine, and then fell in love with each other. According to The Wall Street Journal, one day in 2002 they took a break for lunch, got married, and then returned in the afternoon to their laboratory to finish an experiment — just one more among many conducted over 30 years. Each experiment was one more possible step toward their ultimate dream until finally, in 2020, they achieved that dream: their mRNA vaccine for COVID-19 proved to be very safe and effective.

Holding hard to their dreams

Whichever path scientists who achieve lifesaving breakthroughs travel, they often endure disinterest, like Fleming, or repeated skepticism, ridicule, and rejection, like Karikó, Weissman, Şahin, and Turëci. Only through sheer persistence did these scientists bring their dreams to life. They have been rewarded with fame and wealth and something even more valuable: the knowledge that because of their work hundreds of millions of people around the world never got sick, and millions never died before their time.

Of course, a relentless obsession with an improbable dream fails to pay off for many scientists. Their ideas, while quite brilliant, in the end are proved wrong: nature doesn’t turn out to operate the way they predicted. In the end, their beautiful theory is murdered by a brutal gang of facts.

Still other scientific dreamers ultimately prove to have been on the right track all along and would have achieved their dream — if only they had done the experiment a little differently, if only they had persisted a little longer, or if only the support for their work had not run out. As a result, neither they nor the rest of us benefitted from what would have been — until other scientists rediscovered their work years later.

Ultimately, scientific breakthroughs are possible only if a society is willing to invest in dreamers, recognizing that not all investments will lead to major breakthroughs. However, the investments that do lead to breakthroughs bring an economic return that is far greater than the investment — as well as preventing suffering and death and changing the world.

Want to participate in COVID-19 research? Download the COVID Symptom Study app to help researchers track symptoms and hot spots across the US. Click here for information.

Ever read a headline that catches your eye but then found the story itself disappointing? Or worse, did you feel that the dramatic headline was utterly misleading? Yeah, me too.

The impact of a well-crafted headline can be big. We often skim the headlines, then decide whether or not to read on.

Previously, I’ve written about how media coverage of drug research can mislead or confuse. Here I’m zooming in on health headlines, which can be equally deceptive. Watch for these pitfalls.

Overstated study findings

• Were humans studied? If a study finds that a drug is safe and effective for an important disease, that’s big news. But what if all of the study subjects were mice? Leaving out this important detail from the headline exaggerates the study’s importance.
• Too much drama. Dramatic terms such as “breakthrough” or “groundbreaking” are common in headlines about medical research. Yet true breakthroughs are quite rare. That’s the nature of science: knowledge tends to accumulate slowly, with each finding building a bit on what came before.
• Going too far. Headlines often make a leap of faith when summarizing a study’s findings. For example, if researchers identify a new type of cell in the blood that increases when a disease is worsening, they may speculate that treatments to reduce those cells might control the disease. “Researchers discover new approach to treatment!” blares the headline. Sure, that could happen someday (see below), but it’s an overstatement when the study wasn’t even assessing treatment.

• Overlooking the most important outcome. Rather than examining how a treatment affects heart disease, let’s say, studies may assess how it affects a risk factor for it. A good example is cholesterol. It’s great if a drug lowers cholesterol, but much better if it lowers the rate of cardiovascular disease and deaths. Headlines rarely capture the important difference between a “proxy measure” (such as a risk factor) and the most important outcome (such as rates of death).

Faulty logic

• A link for illness is not the same as a cause of illness. The distinction between “causation” and an “association” is important. Observational studies can determine whether there is a link (association) between two health issues, such as a link between a symptom (like a headache) and a disease (like stomach ulcers). But that doesn’t mean one actually caused the other. Imagine an observational study that compared thousands of headache sufferers with thousands of people who rarely had headaches. If more people in the frequent headache group also had more stomach ulcers, the headline might boldly declare “Headaches cause ulcers!” A more likely explanation is that people with a lot of headaches are taking aspirin, ibuprofen, and related drugs, which are known causes of ulcers.

Hazy on key details

• Someday isn’t today. Studies of new drugs or devices may be heralded as life-changing for people or practice-changing for doctors. Yet, a closer look often reveals that the new treatment is years away from reaching the market — or it may never get approved at all.
• A work in progress. “Preliminary” is the missing word in many headlines. Studies presented at medical conferences but not yet published in a peer-reviewed medical journal offer preliminary insights. This research, while promising at the time, may ultimately be a scientific dead end.
• Is it a study, a press release, or an ad? It’s hard to tell with some headlines. Press releases or advertisements typically present a positive spin on new findings or treatments. We expect news stories to be more balanced.

One story, many headlines

Here’s a great example of overhyped headlines. A 2021 study presented findings about a pacemaker that treats abnormal heart rhythms for a period of time and then dissolves. Amazing, right? For people who need a pacemaker only temporarily, a dissolving pacemaker could allow them to avoid a surgical procedure to remove it once it was no longer needed.

Three headlines covering this research spun the story this way:

Coming Soon: An Implanted Pacemaker That Dissolves Away After Use

Could people one day get pacemakers that dissolve into the body?

First-ever transient pacemaker harmlessly dissolves in body

But that dissolving pacemaker had never been tried in living humans — an important fact! To test the dissolving pacemaker, the researchers had performed open-heart surgery in rats and dogs, and lab experiments on heart tissue removed from mice, rabbits, and deceased humans.

The first headline demonstrates the pitfall of overpromising on the findings of preliminary research: yes, a dissolving pacemaker might someday be routine in humans, but it’s unlikely to be “coming soon.” And when a headline says “harmlessly dissolves in body,” we might reasonably think this refers to a livinghuman body. Not so.

The bottom line

Why are we constantly bombarded with misleading headlines? A major reason is that headlines attract attention, clicks, reads, subscriptions, and influence essential to media sites. Some writers and editors lean into hype, knowing it attracts more attention. Others may not be trained to read or present medical news carefully enough.

In a world full of misleading health news headlines, here’s my advice: be skeptical. Consider the source and read past the headline before buying in. And if your go-to media often serves up misleading headlines, consider changing channels or crossing that news source off your list.

By 2050, 13.8 million people in the US will likely have Alzheimer’s disease, and two-thirds will be women. The economic cost is staggering, as it is estimated to rise to more than $2 trillion. Women are at the epicenter of this because the economic threat is especially dire for women, given they are an increasingly powerful element of our global economy and the vast majority of unpaid caregivers. Thus, maintaining intact memory starting early in midlife with the transition to menopause is critical not only for women themselves, but also for their families, society, and our economic health.

Preventing memory decline starts in early midlife

The decline in cognitive ability is not limited to neurodegenerative diseases like Alzheimer’s disease (AD), but also part of healthy aging, with consequences for our quality of life. Most studies of aging and cognitive decline, particularly studies of AD, begin in people in their 70s. However, understanding factors that happen earlier in life, and how they impact age-related brain changes, is critical for developing prevention strategies for one of the major public health challenges of our time.

What happens to women’s brains through the transition into menopause?

In addition to chronological aging, women undergo reproductive aging in early midlife: menopause, during which they experience a depletion over time of ovarian hormones such as estradiol, the primary form of estrogen that works in the brain. Our research team and others have demonstrated that estradiol directly relates to changes in memory performance and reorganization of our brain circuitry that regulates memory function. Thus, women and men undergo different aging processes, especially in early midlife when reproductive aging is more critical for women than chronological aging. However, cognitive aging is rarely considered a women’s health issue. This is essential, because viewing brain aging as beginning in early midlife, and understanding the impact of menopause on the brain, will allow for development of strategies to prevent memory loss for women.

On average, women perform better than men on measures of verbal memory, beginning as early as post-puberty. However, women’s advantage for verbal memory performance is reduced with menopause. Many women report increased forgetfulness and “brain fog” during the menopausal transition. All women eventually undergo menopause, but there is a large age range for when it begins (from late 40s to early 60s), and substantial variation in women’s experience of its impact.

Over the last 15 years, an increasing number of studies are mapping out the intricate ways in which menopause affects the brain and what helps maintain intact memory. For example, menopause can affect how brain cells are generated, connect with each other, and even die, and these processes impact brain regions that are critical for memory. Menopause also lowers the level of glucose in the brain, the primary fuel used by brain cells. The brain then looks to other metabolic sources to provide the necessary fuel to function — that is, the brain adapts to a new hormonal environment in order to maintain functioning.

Further, women with other medical conditions like diabetes and hypertension are at increased risk for cognitive decline. Research into understanding this is focusing, in part, on how the brain and body share similar processes to produce energy to function (metabolism), and how blood pressure and other aspects of the vascular system function similarly in the brain and body.

Can hormone replacement treatment help?

Research shows that timing matters. Initiation of hormone replacement (HR) in perimenopause (roughly four to eight years before menopause) or early menopause may have positive effects on brain activity and memory function, although systematic HR trials have not been conducted during perimenopause. Initiation of HR in late menopause may have adverse effects on the brain, and increase risk of disorders like Alzheimer’s disease. Research is critically needed to establish the most effective timing of administration, hormonal formula, dose, route of administration (for example, orally or by skin patch), and duration.

Further, to date much of the HR research has been conducted in healthy women, and little is known about its impact in women with chronic diseases such as diabetes and hypertension. Finally, there may be differences in responses in women who are genetically at high risk for brain disorders, like AD, that show increased benefits for using HR. Research shows us that one size does not fit all, and precision medicine is needed to identify which women may benefit the most. One example is for women with bilateral removal of the ovaries, particularly at a young age, for whom HR has been found to be very beneficial for brain function. In some women HR may not be an option, and alternative mechanisms may need to be identified, such as targeting levels of glucose and other effects associated with estradiol regulation of the brain.

What can women do to maintain brain health?

There are three major pillars for maintaining intact memory: effortful physical activity, effortful cognitive activity, and social contact. Research shows that the first two of these have direct beneficial effects on the brain, even at the level of cellular function. Social contact is another form of keeping our brains active by external stimuli, novel experiences, and perspectives outside of ourselves. Dietary habits (such as the Mediterranean diet, or intake of omega-3 fatty acids like in fish oil) have also had beneficial effects on memory function. The good news is that these are modifiable lifestyle habits, which may be particularly important for women with hypertension or diabetes who are at higher risk for cognitive decline.

Finally, adequate sleep (currently suggested as seven hours a night) is critical for brain health. Research has shown that during certain periods of sleep, learning is consolidated; that is, sleep plays a key role in storing and maintaining what we learned during the day, and even helps in clearing the brain of amyloid, one of the markers of potential AD pathology. More research is required to fully understand the beneficial impacts of these modifiable lifestyle factors. However, the time to start incorporating them into your life is now.

Editor's note: In this blog post, Dr. Sharon Levy interviews her son Isaiah Levy, a college student. We appreciate Isaiah’s insights and comments on social media's impact on teens and young adults.

It is hard to remember (or for younger people, hard to imagine) a world without social media, but indeed such a world once existed — and in fact, it is the world humans evolved in.

Humans are social animals. Friendly interactions release dopamine in our brains’ reward centers to get us to repeat the behavior. Until recently, that feedback loop suited us very well, with little opportunity to get off track. Social media changed things by providing the opportunity for nearly infinite interactions. This excess exploits our natural inclination for social contact in the same way that sweets exploit our natural drive to eat ripe fruit. Too much refined sugar can cause a cascade of medical problems; too much social media can also affect health — especially mental health.

Beyond sheer volume, social media interactions are qualitatively different from in-person meetings. For one thing, social media platforms have developed easy opportunities for viewers to react to content, resulting in objective feedback metrics for the content creator. Because the denominator is essentially infinite, no matter how many likes a post gets, the numerator may not feel like enough. Feeling insufficient, not liked enough, judged by others, or excluded from an "in group" takes a heavy toll on mental health.

For perspective from a digital native, I posed questions about social media to my son Isaiah Levy, a computer science major at New York University.

What do you see as the benefits of social media?

Theoretically, social media can connect people across the globe at scale, presenting an opportunity for users to form relationships beyond their geographic boundaries. Popular social media platforms can also provide a stage with a potential audience of one billion eyes. Social media offers tremendous potential for people who want to be noticed. However, most connections are extensions of our real-life relationships, and many users say that social media enriches friendships. For example, a Pew survey found that a majority of teenage respondents said that Instagram enhanced their connections with people they already knew (many of whom are classmates).

Why is Instagram so popular with young people?

Web developers and graphic designers created Instagram using sophisticated algorithms and attractive visual presentation, to keep users engaged and interacting with its nearly limitless content for as long as possible. According to surveys done by Facebook (owner of Instagram), youth describe Instagram as current, friendly, trendy, and creative. Many teens say that Instagram helps define who they are and makes them feel more connected to the people they know. Another significant source of Instagram's allure, particularly for younger users, are the objective feedback measures that can make users feel important or of high social status.

The flip side is that the drive for attention creates its own problems. The Pew survey linked to above found that more than one-third of teen Instagram users said they feel pressure to post content that will get a lot of likes and comments, and more than 40% feel pressure to only post content that makes them look good. According to Facebook’s own internal surveys, more than 13% of teen girls said that Instagram worsens suicidal thoughts, and 17% said their eating disorders got worse with Instagram use.

As the government considers regulating social media, what suggestions do you have in regard to protecting mental health?

Government regulations should protect our freedom of expression while mediating risks, especially to children. The government could consider regulating some of the advanced algorithms that social media corporations use to increase user time expenditure (and thus profits). For example, "infinite swiping" is a design feature that continuously pushes forward new content after a user has exhausted content from the people they follow. These tactics pose serious threats. Just like use of alcohol, nicotine, or drugs, the act of swiping triggers neurological reward. Over time, the brain learns to seek social media instead of more natural rewards, putting users at risk of dissociation with meaningful priorities. As with drug addiction, younger users are at greatest risk. Government regulation of the most sticky algorithms would help promote a healthier balance for users. Deciding which algorithms to ban and how to implement such a ban is certainly a difficult task, and the solution will not be perfect; however, given what we know of the impact of social media on children’s mental health, it should be a federal priority.

While the government grapples with regulation, parents can step in. First, set a good example by putting your own screens down when interacting with your children. Talk to your teen about the pros and cons of social media: while it can be fun, it can also become a distraction. Set limits on your child’s social media use. Most importantly, talk to your children about their experiences, including who they are interacting with and what they are talking about. We know social media can harm mental health, so be on the lookout and intervene if you have concerns.

Insomnia is a sleep disorder that affects approximately 10% of adults in the United States. It is characterized by difficulty with falling asleep, staying asleep, and/or waking up too early, at least three times per week for a period of three months or more. Contrary to some beliefs that insomnia will get better by itself over time, evidence suggests that it will persist if not actively treated. In one study, 37.5% of patients with insomnia reported that their insomnia was still a problem five years later.

What are common treatment options used for insomnia?

Perhaps the most common nonpharmacological intervention used for insomnia is something called sleep hygiene. It describes a series of good sleep habits to engage in (such as keeping your bedroom quiet at night) and ones to avoid (turning off electronic devices before going to bed).

Unfortunately, as many patients know, sleep hygiene is not a very effective treatment for insomnia when implemented by itself. When sleep hygiene is used as one part of a multimodal approach, such as cognitive behavioral therapy for insomnia, it can be an effective complement to other important strategies. While cognitive behavioral therapy for insomnia is recommended as the gold-standard treatment by the American Academy of Sleep Medicine and the American College of Physicians, finding a clinician with expertise in behavioral sleep medicine can be a challenge — even via telemedicine.

Integrative treatment approaches are popular

Many people are interested in pursuing other treatment options for insomnia that do not involve prescription medications. Increasing evidence suggests that a number of approaches may be beneficial, including mindfulness-based practices and mind-body movement practices like yoga. Some people may use dietary supplements such as valerian, melatonin, chamomile, and cannabis, though evidence is more limited regarding their efficacy. You should always tell your doctor if you are taking any dietary supplements, as these may interact with other prescription medications.

An integrative option for people with insomnia and a psychiatric disorder

Insomnia is a common issue for people with a psychiatric disorder, possibly because of overlapping neurobiology. For example, someone with insomnia is 10 times more likely than someone without insomnia to also have depression. Among patients receiving psychiatric care, compression and weight have been used therapeutically. It has been hypothesized that the calming (and possibly sleep-promoting) effects of such an approach may be similar to what is experienced with acupressure or massage.

A team of researchers at the Karolinska Institute in Stockholm, Sweden conducted a study to determine whether a weighted metal chain blanket could improve insomnia symptoms compared to a light plastic chain blanket. They recruited outpatients with elevated insomnia symptoms who were being treated for one of several mood disorders: major depressive disorder, bipolar disorder, generalized anxiety disorder, or attention deficit hyperactivity disorder (ADHD).

Participants were randomly assigned to receive either a weighted metal chain blanket or a light blanket with plastic chains that were sewn on, which were the same shape and size as the metal chains on the weighted blanket. Those who were provided with a weighted metal chain blanket first tried on an 8-kilogram (17.6 pound) blanket. If this was too heavy, a 6-kilogram (13.2 pound) blanket was then provided. Over a four-week period, their sleep was assessed using surveys and a wrist-based device called an actigraph.

What did the researchers learn?

Participants who used the weighted metal chain blanket reported that their insomnia symptom severity declined significantly, while those who had used the light blanket did not experience such notable improvements. Furthermore, depressive symptoms and anxiety symptoms decreased much more for those who used the weighted blanket than those who used the light blanket. This secondary finding is consistent with other work showing that interventions designed to treat insomnia can have a meaningful impact on mood.

These promising findings are tempered by data showing that there were no significant improvements to key insomnia metrics, such as the amount of time spent awake after falling asleep, when sleep was tracked objectively using the actigraph. Other research conducted in children has also failed to demonstrate that weighted blankets significantly change sleep outcomes when measured using an actigraph.

Should you buy a weighted blanket?

While these findings are intriguing, more research is needed. It is important to note that there is a very real placebo effect for insomnia symptoms. This means that if you are someone who believes a weighted blanket could have a positive effect on your sleep tonight… well, it's quite possible that it will. For healthy adults, weighted blankets are considered safe as long as the individual can lift the blanket off when necessary. Because sleep is such a subjective experience, the cost of a weighted blanket may be money well spent — as long as you don’t forget that there are other options available to treat insomnia, with much more research data to support their effectiveness.