Body-on-a-chip, prime editing, and gut microbes all are poised to make a big impact in 2020.
1. Happening Now: Body-on-a-Chip Technology Is Enabling Safer Drug Trials and Better Cancer Research
Researchers have increasingly used the technology known as "lab-on-a-chip" or "organ-on-a-chip" to test the effects of pharmaceuticals, toxins, and chemicals on humans. Rather than testing on animals, which raises ethical concerns and can sometimes be inaccurate, and human-based clinical trials, which can be expensive and difficult to iterate, scientists turn to tiny, micro-engineered chips—about the size of a thumb drive.
It's possible that doctors could one day take individual cell samples and create personalized treatments, testing out any medications on the chip.
The chips are lined with living samples of human cells, which mimic the physiology and mechanical forces experienced by cells inside the human body, down to blood flow and breathing motions; the functions of organs ranging from kidneys and lungs to skin, eyes, and the blood-brain barrier.
A more recent—and potentially even more useful—development takes organ-on-a-chip technology to the next level by integrating several chips into a "body-on-a-chip." Since human organs don't work in isolation, seeing how they all react—and interact—once a foreign element has been introduced can be crucial to understanding how a certain treatment will or won't perform. Dr. Shyni Varghese, a MEDx investigator at the Duke University School of Medicine, is one of the researchers working with these systems in order to gain a more nuanced understanding of how multiple different organs react to the same stimuli.
Her lab is working on "tumor-on-a-chip" models, which can not only show the progression and treatment of cancer, but also model how other organs would react to immunotherapy and other drugs. "The effect of drugs on different organs can be tested to identify potential side effects," Varghese says. In addition, these models can help the researchers figure out how cancers grow and spread, as well as how to effectively encourage immune cells to move in and attack a tumor.
One body-on-a-chip used by Dr. Varghese's lab tracks the interactions of five organs—brain, heart, liver, muscle, and bone.
As their research progresses, Varghese and her team are looking for ways to maintain the long-term function of the engineered organs. In addition, she notes that this kind of research is not just useful for generalized testing; "organ-on-chip technologies allow patient-specific analyses, which can be used towards a fundamental understanding of disease progression," Varghese says. It's possible that doctors could one day take individual cell samples and create personalized treatments, testing out any medications on the chip for safety, efficacy, and potential side effects before writing a prescription.
2. Happening Soon: Prime Editing Will Have the Power to "Find and Replace" Disease-Causing Genes
Biochemist David Liu made industry-wide news last fall when he and his lab at MIT's Broad Institute, led by Andrew Anzalone, published a paper on prime editing: a new, more focused technology for editing genes. Prime editing is a descendant of the CRISPR-Cas9 system that researchers have been working with for years, and a cousin to Liu's previous innovation—base editing, which can make a limited number of changes to a single DNA letter at a time.
By contrast, prime editing has the potential to make much larger insertions and deletions; it also doesn't require the tweaked cells to divide in order to write the changes into the DNA, which could make it especially suitable for central nervous system diseases, like Parkinson's.
Crucially, the prime editing technique has a much higher efficiency rate than the older CRISPR system, and a much lower incidence of accidental insertions or deletions, which can make dangerous changes for a patient.
It also has a very broad potential range: according to Liu, 89% of the pathogenic mutations that have been collected in ClinVar (a public archive of human variations) could, in principle, be treated with prime editing—although he is careful to note that correcting a single genetic mutation may not be sufficient to fully treat a genetic disease.
Figuring out just how prime editing can be used most effectively and safely will be a long process, but it's already underway. The same day that Liu and his team posted their paper, they also made the basic prime editing constructs available for researchers around the world through Addgene, a plasmid repository, so that others in the scientific community can test out the technique for themselves. It might be years before human patients will see the results, and in the meantime, significant bioethical questions remain about the limits and sociological effects of such a powerful gene-editing tool. But in the long fight against genetic diseases, it's a huge step forward.
3. Happening When We Fund It: Focusing on Microbiome Health Could Help Us Tackle Social Inequality—And Vice Versa
The past decade has seen a growing awareness of the major role that the microbiome, the microbes present in our digestive tract, play in human health. Having a less-healthy microbiome is correlated with health risks like diabetes and depression, and interventions that target gut health, ranging from kombucha to fecal transplants, have cropped up with increasing frequency.
New research from the University of Maine's Dr. Suzanne Ishaq takes an even broader view, arguing that low-income and disadvantaged populations are less likely to have healthy, diverse gut bacteria, and that increasing access to beneficial microorganisms is an important juncture of social justice and public health.
"Basically, allowing people to lead healthy lives allows them to access and recruit microbes."
"Typically, having a more diverse bacterial community is associated with health, and having fewer different species is associated with illness and may leave you open to infection from bacteria that are good at exploiting opportunities," Ishaq says.
Having a healthy biome doesn't mean meeting one fixed ratio of gut bacteria, since different combinations of microbes can generate roughly similar results when they work in concert. Generally, "good" microbes are the ones that break down fiber and create the byproducts that we use for energy, or ones like lactic acid bacteria that work to make microbials and keep other bacteria in check. The microbial universe in your gut is chaotic, Ishaq says. "Microbes in your gut interact with each other, with you, with your food, or maybe they don't interact at all and pass right through you." Overall, it's tricky to name specific microbial communities that will make or break someone's health.
There are important corollaries between environment and biome health, though, which Ishaq points out: Living in urban environments reduces microbial exposure, and losing the microorganisms that humans typically source from soil and plants can reduce our adaptive immunity and ability to fight off conditions like allergies and asthma. Access to green space within cities can counteract those effects, but in the U.S. that access varies along income, education, and racial lines. Likewise, lower-income communities are more likely to live in food deserts or areas where the cheapest, most convenient food options are monotonous and low in fiber, further reducing microbial diversity.
Ishaq also suggests other areas that would benefit from further study, like the correlation between paid family leave, breastfeeding, and gut microbiota. There are technical and ethical challenges to direct experimentation with human populations—but that's not what Ishaq sees as the main impediment to future research.
"The biggest roadblock is money, and the solution is also money," she says. "Basically, allowing people to lead healthy lives allows them to access and recruit microbes."
That means investment in things we already understand to improve public health, like better education and healthcare, green space, and nutritious food. It also means funding ambitious, interdisciplinary research that will investigate the connections between urban infrastructure, housing policy, social equity, and the millions of microbes keeping us company day in and day out.
Residents of Fountain Hills, a small town near Phoenix, Arizona, fought against the night sky pollution to restore their Milky Way skies.
Light pollution is defined as the excessive or wasteful use of artificial light.
Light-emitting diodes (LEDs) -- which became commercially available in 2002 and rapidly gained popularity in offices, schools, and hospitals when their price dropped six years later — inadvertently fueled the surge in light pollution. As traditional light sources like halogen, fluorescent, mercury, and sodium vapor lamps have been phased out or banned, LEDs became the main source of lighting globally in 2019. Switching to LEDs has been lauded as a win-win decision. Not only are they cheap but they also consume a fraction of electricity compared to their traditional counterparts.
But as cheap LED installations became omnipresent, they increased light pollution. “People have been installing LEDs thinking they are making a positive change for the environment. But LEDs are a lot brighter than traditional light sources,” explains Ashley Wilson, director of conservation at the International Dark-Sky Association (IDA). “Despite being energy-efficient, they are increasing our energy consumption. No one expected this kind of backlash from switching to LEDs.”
Light pollution impacts the circadian rhythms of all living beings — the natural internal process that regulates the sleep–wake cycle.
Currently, more than 80 percent of the world lives under light-polluted skies. In the U.S. and Europe, that figure is above 99 percent.
According to the IDA, $3 billion worth of electricity is lost to skyglow every year in the U.S. alone — thanks to unnecessary and poorly designed outdoor lighting installations. Worse, the resulting light pollution has insidious impacts on humans and wildlife — in more ways than one.
Disrupting the brain’s clock
Light pollution impacts the circadian rhythms of all living beings—the natural internal process that regulates the sleep–wake cycle. Humans and other mammals have neurons in their retina called intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells collect information about the visual world and directly influence the brain’s biological clock in the hypothalamus.
The ipRGCs are particularly sensitive to the blue light that LEDs emit at high levels, resulting in suppression of melatonin, a hormone that helps us sleep. A 2020 JAMA Psychiatry study detailed how teenagers who lived in areas with bright outdoor lighting at night went to bed late and slept less, which made them more prone to mood disorders and anxiety.
“Many people are skeptical when they are told something as ubiquitous as lights could have such profound impacts on public health,” says Gena Glickman, director of the Chronobiology, Light and Sleep Lab at Uniformed Services University. “But when the clock in our brains gets exposed to blue light at nighttime, it could result in a lot of negative consequences like impaired cognitive function and neuro-endocrine disturbances.”
In the last 12 years, several studies indicated that light pollution exposure is associated with obesity and diabetes in humans and animals alike. While researchers are still trying to understand the exact underlying mechanisms, they found that even one night of too much light exposure could negatively affect the metabolic system. Studies have linked light pollution to a higher risk of hormone-sensitive cancers like breast and prostate cancer. A 2017 study found that female nurses exposed to light pollution have a 14 percent higher risk of breast cancer. The World Health Organization (WHO) identified long-term night shiftwork as a probable cause of cancer.
“We ignore our biological need for a natural light and dark cycle. Our patterns of light exposure have consequently become different from what nature intended,” explains Glickman.
Circadian lighting systems, designed to match individuals’ circadian rhythms, might help. The Lighting Research Center at Rensselaer Polytechnic Institute developed LED light systems that mimic natural lighting fluxes, required for better sleep. In the morning the lights shine brightly as does the sun. After sunset, the system dims, once again mimicking nature, which boosts melatonin production. It can even be programmed to increase blue light indoors when clouds block sunlight’s path through windows. Studies have shown that such systems might help reduce sleep fragmentation and cognitive decline. People who spend most of their day indoors can benefit from such circadian mimics.
When Diane Turnshek moved to Pittsburgh, she found it almost impossible to see a clear night sky because the city’s countless lights created a bright dome of light called skyglow.
Diane Turnshek
Leading to better LEDs
Light pollution disrupts the travels of millions of migratory birds that begin their long-distance journeys after sunset but end up entrapped within the sky glow of cities, becoming disoriented. A 2017 study in Nature found that nocturnal pollinators like bees, moths, fireflies and bats visit 62 percent fewer plants in areas with artificial lights compared to dark areas.
“On an evolutionary timescale, LEDs have triggered huge changes in the Earth’s environment within a relative blink of an eye,” says Wilson, the director of IDA. “Plants and animals cannot adapt so fast. They have to fight to survive with their existing traits and abilities.”
But not all types of LEDs are inherently bad -- it all comes down to how much blue light they emit. During the day, the sun emits blue light waves. By sunset, red and orange light waves become predominant, stimulating melatonin production. LED’s artificial blue light, when shining at night, disrupts that. For some unknown reason, there are more bluer color LEDs made and sold.
“Communities install blue color temperature LEDs rather than redder color temperature LEDs because more of the blue ones are made; they are the status quo on the market,” says Michelle Wooten, an assistant professor of astronomy at the University of Alabama at Birmingham.
Most artificial outdoor light produced is wasted as human eyes do not use them to navigate their surroundings.
While astronomers and the IDA have been educating LED manufacturers about these nuances, policymakers struggle to keep up with the growing industry. But there are things they can do—such as requiring LEDs to include dimmers. “Most LED installations can be dimmed down. We need to make the dimmable drivers a mandatory requirement while selling LED lighting,” says Nancy Clanton, a lighting engineer, designer, and dark sky advocate.
Some lighting companies have been developing more sophisticated LED lights that help support melatonin production. Lighting engineers at Crossroads LLC and Nichia Corporation have been working on creating LEDs that produce more light in the red range. “We live in a wonderful age of technology that has given us these new LED designs which cut out blue wavelengths entirely for dark-sky friendly lighting purposes,” says Wooten.
Dimming the lights to see better
The IDA and advocates like Turnshek propose that communities turn off unnecessary outdoor lights. According to the Department of Energy, 99 percent of artificial outdoor light produced is wasted as human eyes do not use them to navigate their surroundings.
In recent years, major cities like Chicago, Austin, and Philadelphia adopted the “Lights Out” initiative encouraging communities to turn off unnecessary lights during birds’ peak migration seasons for 10 days at a time. “This poses an important question: if people can live without some lights for 10 days, why can’t they keep them turned off all year round,” says Wilson.
Most communities globally believe that keeping bright outdoor lights on all night increases security and prevents crime. But in her studies of street lights’ brightness levels in different parts of the US — from Alaska to California to Washington — Clanton found that people felt safe and could see clearly even at low or dim lighting levels.
Clanton and colleagues installed LEDs in a Seattle suburb that provided only 25 percent of lighting levels compared to what they used previously. The residents reported far better visibility because the new LEDs did not produce glare. “Visual contrast matters a lot more than lighting levels,” Clanton says. Additionally, motion sensor LEDs for outdoor lighting can go a long way in reducing light pollution.
Flipping a switch to preserve starry nights
Clanton has helped draft laws to reduce light pollution in at least 17 U.S. states. However, poor awareness of light pollution led to inadequate enforcement of these laws. Also, getting thousands of counties and municipalities within any state to comply with these regulations is a Herculean task, Turnshek points out.
Fountain Hills, a small town near Phoenix, Arizona, has rid itself of light pollution since 2018, thanks to the community's efforts to preserve dark skies.
Until LEDs became mainstream, Fountain Hills enjoyed starry skies despite its proximity to Phoenix. A mountain surrounding the town blocks most of the skyglow from the city.
“Light pollution became an issue in Fountain Hills over the years because we were not taking new LED technologies into account. Our town’s lighting code was antiquated and out-of-date,” says Vicky Derksen, a resident who is also a part of the Fountain Hills Dark Sky Association founded in 2017. “To preserve dark skies, we had to work with the entire town to update the local lighting code and convince residents to follow responsible outdoor lighting practices.”
Derksen and her team first tackled light pollution in the town center which has a faux fountain in the middle of a lake. “The iconic centerpiece, from which Fountain Hills got its name, had the wrong types of lighting fixtures, which created a lot of glare,” adds Derksen. They then replaced several other municipal lighting fixtures with dark-sky-friendly LEDs.
The results were awe-inspiring. After a long time, residents could see the Milky Way with crystal clear clarity. Star-gazing activities made a strong comeback across the town. But keeping light pollution low requires constant work.
Derksen and other residents regularly measure artificial light levels in
Fountain Hills. Currently, the only major source of light pollution is from extremely bright, illuminated signs which local businesses had installed in different parts of the town. While Derksen says it is an uphill battle to educate local businesses about light pollution, Fountain Hills residents are determined to protect their dark skies.
“When a river gets polluted, it can take several years before clean-up efforts see any tangible results,” says Derksen. “But the effects are immediate when you work toward reducing light pollution. All it requires is flipping a switch.”