What it takes to achieve world-changing scientific breakthroughs

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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.

Do weighted blankets help with insomnia?

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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.

Time to stock up on zinc?

As if stubbornly high rates of COVID-19 aren’t giving us enough to worry about, welcome to cold and flu season!

Yes, colds and influenza, two well-known upper respiratory infections, will soon be on the rise. Last year we saw remarkably low rates of flu. Many experts don’t think we’ll be so lucky this year.

Think zinc?

A new analysis reviewing available research suggests that over-the-counter zinc supplements could be one way to make cold and flu season a bit easier. Of course, this isn’t the first study to look into zinc as an antiviral remedy, including for COVID-19. But the results of past research have been mixed at best: some studies find modest benefit, others find no benefit, and the quality of the research has been low. Also, some people experience bothersome side effects from zinc, such as upset stomach, nausea, and in some cases, loss of the sense of smell.

What did the study say?

Published in November 2021 in BMJ Open, the study looks at zinc for preventing or treating colds and flulike illness. The researchers reviewed more than 1,300 previous studies and narrowed the analysis down to 28 well-designed trials, which included more than 5,000 study subjects. Here’s what they found:

For preventing colds and flu-like illness:

  • Compared with placebo, zinc supplements or nasal spray zinc are associated with fewer upper respiratory infections. The estimated effect was modest: about one infection was prevented for every 20 people using zinc. The strength of the evidence for these findings is considered low.
  • A few studies suggest preventive effects were largest for reducing severe symptoms, such as fever and flulike illness. It’s worth noting that the studies didn’t confirm whether participants had flu infections.
  • Small studies of intentional exposure to cold virus found that zinc did not prevent colds.

For treating colds and flulike illness:

  • Compared with placebo, those who took zinc had symptoms go away about two days sooner. The study estimated that of 100 people with upper respiratory infections, an extra 19 people would have completely recovered by day seven due to zinc treatment. The strength of the evidence for these findings is considered low.
  • Some measures of symptom severity were lower for those treated with zinc (versus placebo): on day three of the infection, those taking zinc had milder symptoms. Further, there was an 87% lower risk of severe symptoms among those taking zinc. However, the daily average symptom severity was similar between those taking zinc and those taking placebo. The data quality and certainty of these findings were low to moderate.

What else to consider before stocking up on zinc

While these findings suggest promise in the ability of zinc to prevent or temper cold and flulike illness, here are other points to consider:

  • Side effects. Side effects occurred more often in those taking zinc (versus placebo), including nausea and mouth or nose irritation. Fortunately, none were serious. But they might be bothersome enough for some people to stop using zinc.
  • Cost. Zinc supplements are generally inexpensive. A daily dose of zinc lozenges for a month may cost less than $2/month (though I also found certain brands for sale online for as much as $75/month).
  • Zinc deficiency. Study subjects either had normal zinc levels or were otherwise considered unlikely to be zinc deficient. There’s a big difference between taking a zinc supplement to prevent or treat respiratory infections and taking it because your body lacks enough of the mineral. Zinc deficiency is more likely among people with poor nutrition or digestive conditions that interfere with mineral absorption; they require supplementation to avoid serious complications such as impaired immune function and poor wound healing.
  • Different doses or types. Additional research is needed to determine the best way to take zinc.
  • COVID-19. None of the studies in this analysis assessed the impact of zinc supplements on SARS-CoV-2, so these conclusions do not apply to COVID-19.

You know the drill

Perhaps this new analysis will convince you to take zinc this winter. Or perhaps you’re still skeptical. Either way, don’t forget tried and true preventive measures and treatments during cold and flu season, including these:

  • Get a flu shot
  • Wash your hands frequently
  • Avoid contact, maintain physical distance, and wear a mask around people who are sick
  • Get plenty of sleep
  • Choose a healthy diet.

If you do get sick:

  • Stay home if possible
  • Wear a mask if you can’t avoid contact with others
  • Drink plenty of fluids
  • Take over-the-counter cold and flu remedies to reduce symptoms
  • Contact your doctor if you have symptoms of the flu; early treatment can shorten the duration of the illness. In addition, other conditions (especially COVID-19) should be ruled out.

Many of the measures recommended for cold and flu season overlap with those recommended to prevent or treat COVID-19.

The bottom line

Colds and flulike illnesses afflict millions every winter. You might feel as though it’s inevitable you’ll be among them. But you may be able to spare yourself the misery by following some simple, safe, and common-sense measures. As evidence mounts in its favor, perhaps these measures should include zinc.

As for me, I remain steadfastly on the fence. But it wouldn’t take much — perhaps one more large, well-designed, randomized controlled trial — to push me onto the zinc bandwagon.