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CRISPR and other new technologies open doors for drug development, but which diseases get prioritized? It comes down to money and science

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CRISPR and other new technologies open doors for drug development, but which diseases get prioritized? It comes down to money and science

So many diseases to treat, so little money and time.
Andriy Onufriyenko/Moment via Getty Images

C. Michael White, University of Connecticut

Prescription and vaccines revolutionized care, dramatically decreasing death from disease and improving quality of across the globe. But how do researchers, universities and hospitals, and the pharmaceutical industry decide which diseases to pursue developing drugs for?

In my work as director of the Health Outcomes, Policy, and Evidence Synthesis group at the University of Connecticut School of Pharmacy, I assess the effectiveness and safety of different treatment options to clinicians and make informed decisions. My colleagues and I study ways to create new drug molecules, deliver them into the body and improve their effectiveness while reducing their potential harms. Several factors determine which avenues of drug discovery that people in research and pharmaceutical companies focus on.

Funding drives research decisions

Research funding amplifies the pace of scientific discovery needed to create new treatments. Historically, major supporters of research like the National Institutes of Health, pharmaceutical industry and private foundations funded studies on the most common conditions, like heart disease, diabetes and mental health disorders. A breakthrough therapy would help millions of people, and a small markup per dose would generate hefty profits.

As a consequence, research on rare diseases was not well-funded for decades because it would help fewer people and the costs of each dose had to be very high to turn a profit. Of the more than 7,000 known rare diseases, defined as fewer than 200,000 people affected in the U.S., only 34 had a therapy approved by the Food and Drug Administration before 1983.

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The passage of the Orphan Drug Act changed this trend by offering tax credits, research incentives and prolonged patent lives for companies actively developing drugs for rare diseases. From 1983 to 2019, 724 drugs were approved for rare diseases.

Person sluicing a bucket of ice water over another person's head
The viral ALS ice bucket in 2014 was a fundraising success.
Elise Amendola/AP Photo

Emerging social issues or opportunities can significantly affect funding available to develop drugs for certain diseases. When COVID-19 raged across the world, funding from Operation Warp Speed led to vaccine in record time. Public awareness campaigns such as the ALS ice bucket challenge can also directly raise money for research. This viral social media campaign provided 237 scientists nearly US$90 million in research funding from 2014 to 2018, which led to the discovery of five genes connected amyotrophic lateral sclerosis, commonly called Lou Gehrig’s disease, and new clinical trials.

How science approaches drug development

To create breakthrough treatments, researchers need a basic understanding of what disease processes they need to enhance or block. This requires developing cell and animal models that can simulate human biology.

It can take many years to vet potential treatments and develop the finished drug product ready for testing in people. Once scientists identify a potential biological target for a drug, they use high-throughput screening to rapidly assess hundreds of chemical compounds that may have a desired effect on the target. They then modify the most promising compounds to enhance their effects or reduce their toxicity.

When these compounds have lackluster results in the lab, companies are likely to halt development if the estimated potential revenue from the drug is less than the estimated cost to improve the treatments. Companies can charge more money for drugs that dramatically reduce deaths or disability than for those that only reduce symptoms. And researchers are more likely to continue working on drugs that have a greater potential to help patients. In order to obtain FDA approval, companies ultimately need to show that the drug causes more for patients than harms.

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Casgevy, a CRISPR-based treatment for sickle cell anemia, is considered a milestone in gene therapy.

Sometimes, researchers know a lot about a disease, but available technology is insufficient to produce a successful drug. For a long time, scientists knew that sickle cell disease results from a defective gene that cells in the bone marrow to produce poorly formed red blood cells, causing severe pain and blood clots. Scientists lacked a way to fix the issue or to work around it with existing methods.

However, in the early 1990s, basic scientists discovered that bacterial cells have a mechanism to identify and edit DNA. With that model, researchers began painstaking work developing a technology called CRISPR to identify and edit genetic sequences in human DNA.

The technology finally progressed to the point where scientists were able to successfully target the problematic gene in patients with sickle cell and edit it to produce normally functioning red blood cells. In December 2023, Casgevy became the first CRISPR-based drug approved by the FDA.

Sickle cell disease made a great target for this technology because it was caused by a single genetic issue. It was also an attractive disease to focus on because it affects around 100,000 people in the U.S. and is costly to society, causing many hospitalizations and lost days of work. It also disproportionately affects Black Americans, a population that has been underrepresented in medical research.

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Real-world drug development

To put all these pieces of drug development into perspective, consider the leading cause of death in the U.S.: cardiovascular disease. Even though there are several drug options available for this condition, there is an ongoing need for more effective and less toxic drugs that reduce the risk of heart attacks and strokes.

In 1989, epidemiologists found that patients with higher levels of bad, or LDL, cholesterol had more heart attacks and strokes than those with lower levels. Currently, 86 million American adults have elevated cholesterol levels that can be treated with drugs, like the popular statins Lipitor (atorvastatin) or Crestor (rosuvastatin). However, statins alone cannot get everyone to their cholesterol goals, and many patients develop unwanted symptoms limiting the dose they can .

Two blister packs of burnt orange pills with days of the week listed on each dose
There are several statins on the market to treat high cholesterol levels.
Peter Dazeley/The Image Bank via Getty Images

So scientists developed models to understand how LDL cholesterol is created in and removed from the body. They found that LDL receptors in the liver removed bad cholesterol from the blood, but a protein called PCSK9 prematurely destroys them, boosting bad cholesterol levels in the blood. This led to the development of the drugs Repathy (evolocumab) and Praluent (alirocumab) that bind to PCSK9 and stop it from working. Another drug, Leqvio (inclisiran), blocks the genetic material coding for PCSK9.

Researchers are also developing a CRISPR-based method to more effectively treat the disease.

The future of drug development

Drug development is driven by the priorities of their funders, be it governments, foundations or the pharmaceutical industry.

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Based on the market, companies and researchers tend to study highly prevalent diseases with devastating societal consequences, such as Alzheimer’s disease and opioid use disorder. But the work of advocacy groups and foundations can enhance research funding for other specific diseases and conditions. Policies like the Orphan Drug Act also create successful incentives to discover treatments for rare diseases.

However, in 2021, 51% of drug discovery spending in the U.S. was directed at only 2% of the population.. How to strike a balance between providing incentives to develop miracle drug therapies for a few people at the expense of the many is a question researchers and policymakers are still grappling with.The Conversation

C. Michael White, Distinguished Professor of Pharmacy Practice, University of Connecticut

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Will your phone one day let you smell as well as see and hear what’s on the other end of a call?

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theconversation.com – Jian Liu, Assistant Professor of Electrical Engineering and Computer Science, of Tennessee – 2024-09-16 07:27:05

Phones that transmit odors seem like a great idea, but careful what you wish for!

Teo Mahatmana/iStock via Getty Images

Jian Liu, University of Tennessee

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Curious Kids is a series for of all ages. If you have a question you’d like an expert to answer, send it to curiouskidsus@theconversation.com.


Is it possible to make a phone through which we can smell, like we can hear and see? – Muneeba K., age 10, Pakistan


Imagine this: You pick up your phone for a call with a friend. Not only can you see their face and hear their voice, but you can also smell the cookies they just baked. It sounds like something out of a science fiction , but could it actually happen?

I’m a computer scientist who studies how machines sense the world.

What phones do now

When you listen to music or to someone on your phone, you can hear the sound through the built-in speakers. These speakers convert digital signals into physical vibrations using a tiny component called a diaphragm. Your ears sense those vibrations as sound waves.

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Your phone also has a screen that displays images and . The screen uses tiny dots known as pixels that consist of three primary colors: red, green and blue. By mixing these colors in different ways, your phone can show you everything from beautiful beach scenes to cute puppies.

Smelling with phones

Now how about the sense of smell? Smells are created by tiny particles called molecules that float through the and reach your nose. Your nose then sends signals to your brain, which identifies the smell.

So, could your phone send these smell molecules to you? Scientists are working on it. Think about how your phone screen works. It doesn’t have every color in the world stored inside it. Instead, it uses just three colors to create millions of different hues and shades.

How your sense of smell works.

Now imagine something similar for smells. Scientists are developing digital scent technology that uses a small number of different cartridges, each containing a specific scent. Just like how pixels mix three colors to create images, these scent cartridges could mix to create different smells.

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Just like images on your phone are made of digital codes that represent combinations of pixels, smells produced by a future phone could be created using digital codes. Each smell could have a specific recipe made up of different amounts of the ingredients in the cartridges.

When you a digital scent code, your phone could mix tiny amounts of the different scents from the cartridges to create the desired smell. This mix would then be released through a small vent on the phone, allowing you to smell it. With just a few cartridges, your phone could potentially create a huge variety of smells, much like how red, green and blue pixels can create countless colors.

Researchers and companies are already working on digital odor makers like this.

The challenges to making smell phones

Creating a phone that can produce smells involves several challenges. One is designing a system that can produce thousands of different smells using only a few cartridges. Another is how to control how strong a scent should be and how long a phone should emit it. And phones will also need to sense odors near them and convert those to digital codes so your friends’ phones can send smells to you.

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The cartridges should also be easy to refill, and the chemicals in them be safe to breathe. These hurdles make it a tricky but exciting area of research.

An odiferous future

Even though we’re not there yet, scientists and engineers are working hard to make smell phones a reality. Maybe one day you’ll be able to not only see and hear your friend’s birthday party over the phone, but also smell the candles they blew out!


Hello, curious kids! Do you have a question you’d like an expert to answer? Ask an adult to send your question to CuriousKidsUS@theconversation.com. Please tell us your name, age and the city where you .

And since curiosity has no age limit – adults, let us know what you’re wondering, too. We won’t be able to answer every question, but we will do our best.The Conversation

Jian Liu, Assistant Professor of Electrical Engineering and Computer Science, University of Tennessee

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The Conversation

a double shot of US history

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theconversation.com – Kyle G. Volk, Professor of History, of Montana – 2024-09-16 07:28:46

a beer in Raceland, La.

Russell Lee for Farm Security Administration/WPA

Kyle G. Volk, University of Montana

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Text saying: Uncommon Courses, from The Conversation

Uncommon Courses is an occasional series from U.S. highlighting unconventional approaches to teaching.

Title of course:

“Intoxication Nation: Alcohol in American History”

What prompted the idea for the course?

I wanted to get students about studying the past by learning about something that is very much a part of their own lives.

Alcohol – somewhat surprisingly to me at first – prominently in my own research on minority rights and U.S. democracy in the mid-19th century. As a result, I knew quite a bit about the temperance movement and conflicts over prohibition during that period. Designing this course allowed me to broaden my expertise.

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What does the course explore?

Prohibition is a must-do subject. Students expect it. But I cover several hundred years of history: from the 17th-century invention of rum – as a byproduct of sugar produced by enslaved people – to the rise of craft beer and craft spirits in the 21st century.

A faded poster with an illustration of a person about to smash a huge bottle of alcohol, and the message 'Close the saloons' at the top.

A temperance poster from the World War I era.

Office of Naval Records and Library via National Archives Catalog

Along the way, I’m thrilled when students get excited about details that allow them to taste a more complicated historical cocktail. For example, they learn why white women’s production of hard cider was crucial to the survival of colonial Virginia. The short answer: Potable was in short supply, alcoholic drinks were far healthier, and white men – and their indentured and enslaved workforce – were busy raising tobacco. It fell to women to turn fruit into salvation.

Why is this course relevant now?

Alcohol remains a big and almost inescapable part of American society. But of late, Americans have been drinking differently – and thinking about drinking differently.

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Examples abound. Alcohol producers, we learn, now face competition from legalized weed. Drinking l evels rose during the COVID-19 pandemic, yet interest is declining among Gen Zers. The “wine mom” culture that brought some mothers together now faces mounting criticism.

And, of course, there’s the never-ending debate about the health benefits and risks of alcohol. Of late, the risks seem to be dominating headlines.

What’s a critical lesson from the course?

Alcohol has been a highly controversial, central aspect of the American experience, shaping virtually all sectors of our society – political and constitutional, business and economic, social and cultural.

What materials does the course feature?

What will the course prepare students to do?

Like any history course, this one aims to develop student’s analytical, written, research and verbal skills. In lots of ways, the topic is just a tool to get students to grow their brains. But I also seek to grow students’ critical awareness of the place of alcohol in their own lives. The course has also informed students’ paths after graduation – some who wound up working in the alcohol industry or recovery .The Conversation

Kyle G. Volk, Professor of History, University of Montana

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Sunflowers make small moves to maximize their Sun exposure − physicists can model them to predict how they grow

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theconversation.com – Chantal Nguyen, Postdoctoral Associate at the BioFrontiers Institute, of Colorado Boulder – 2024-09-13 07:31:40

Sunflowers use tiny movements to follow the Sun’s path throughout the day.

AP Photo/Charlie Riedel

Chantal Nguyen, University of Colorado Boulder

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Most of us aren’t spending our days watching our houseplants grow. We see their signs of only occasionally – a new leaf unfurled, a stem leaning toward the window.

But in the summer of 1863, Charles Darwin lay ill in bed, with nothing to do but watch his plants so closely that he could detect their small movements to and fro. The tendrils from his cucumber plants swept in circles until they encountered a stick, which they proceeded to twine around.

“I am getting very much amused by my tendrils,” he wrote.

This amusement blossomed into a decadeslong fascination with the little-noticed world of plant movements. He compiled his detailed observations and experiments in a 1880 book called “The Power of Movement in Plants.”

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A zig-zagging line showing the movement of a leaf.

A diagram tracking the circumnutation of a leaf over three days.

Charles Darwin

In one study, he traced the motion of a carnation leaf every few hours over the course of three days, revealing an irregular looping, jagged path. The swoops of cucumber tendrils and the zags of carnation leaves are examples of inherent, ubiquitous plant movements called circumnutations – from the Latin circum, meaning circle, and nutare, meaning to nod.

Circumnutations vary in size, regularity and timescale across plant species. But their exact function remains unclear.

I’m a physicist interested in understanding collective behavior in living . Like Darwin, I’m captivated by circumnutations, since they may underlie more complex phenomena in groups of plants.

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Sunflower patterns

A 2017 study revealed a fascinating observation that got my colleagues and me wondering about the role circumnutations could play in plant growth patterns. In this study, researchers found that sunflowers grown in a dense row naturally formed a near-perfect zigzag pattern, with each plant leaning away from the row in alternating directions.

This pattern the plants to avoid shade from their neighbors and maximize their exposure to sunlight. These sunflowers flourished.

Researchers then planted some plants at the same density but constrained them so that they could grow only upright without leaning. These constrained plants produced less oil than the plants that could lean and get the maximum amount of sun.

While farmers can’t grow their sunflowers quite this close together due to the potential for disease spread, in the future they may be able to use these patterns to up with new planting strategies.

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Self-organization and randomness

This spontaneous pattern formation is a neat example of self-organization in nature. Self-organization refers to when initially disordered systems, such as a jungle of plants or a swarm of bees, achieve order without anything controlling them. Order emerges from the interactions between individual members of the system and their interactions with the .

Somewhat counterintuitively, noise – also called randomness – facilitates self-organization. Consider a colony of ants.

Ants secrete pheromones behind them as they crawl toward a food source. Other ants find this food source by the pheromone trails, and they further reinforce the trail they took by secreting their own pheromones in turn. Over time, the ants converge on the best path to the food, and a single trail prevails.

But if a shorter path were to become possible, the ants would not necessarily find this path just by following the existing trail.

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If a few ants were to randomly deviate from the trail, though, they might stumble onto the shorter path and create a new trail. So this randomness injects a spontaneous change into the ants’ system that allows them to explore alternative scenarios.

Eventually, more ants would follow the new trail, and soon the shorter path would prevail. This randomness helps the ants adapt to changes in the environment, as a few ants spontaneously seek out more direct ways to their food source.

A group of honeybees spread out standing on honeycomb.

Beehives are an example of self-organization in nature.

Martin Ruegner/Stone via Getty Images

In biology, self-organized systems can be found at a range of scales, from the patterns of proteins inside cells to the socially complex colonies of honeybees that collectively build nests and forage for nectar.

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Randomness in sunflower self-organization

So, could random, irregular circumnutations underpin the sunflowers’ self-organization?

My colleagues and I set out to explore this question by following the growth of young sunflowers we planted in the lab. Using cameras that imaged the plants every five minutes, we tracked the movement of the plants to see their circumnutatory paths.

We saw some loops and spirals, and lots of jagged movements. These ultimately appeared largely random, much like Darwin’s carnation. But when we placed the plants together in rows, they began to move away from one another, forming the same zigzag configurations that we’d seen in the previous study.

Five plants and a diagram showing loops and jagged lines that represent small movements made by the plants.

Tracking the circumnutations made by young sunflower plants.

Chantal Nguyen

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We analyzed the plants’ circumnutations and found that at any given time, the direction of the plant’s motion appeared completely independent of how it was moving about half an hour earlier. If you measured a plant’s motion once every 30 minutes, it would appear to be moving in a completely random way.

We also measured how much the plant’s leaves grew over the course of two weeks. By putting all of these results together, we sketched a picture of how a plant moved and grew on its own. This information allowed us to computationally model a sunflower and simulate how it behaves over the course of its growth.

A sunflower model

We modeled each plant simply as a circular crown on a stem, with the crown expanding according to the growth rate we measured experimentally. The simulated plant moved in a completely random way, taking a “step” every half hour.

We created the model sunflowers with circumnutations of lower or higher intensity by tweaking the step sizes. At one end of the spectrum, sunflowers were much more likely to take tiny steps than big ones, leading to slow, minimal movement on average. At the other end were sunflowers that are equally as likely to take large steps as small steps, resulting in highly irregular movement. The real sunflowers we observed in our experiment were somewhere in the middle.

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Plants require light to grow and have evolved the ability to detect shade and alter the direction of their growth in response.

We wanted our model sunflowers to do the same thing. So, we made it so that two plants that get too close to each other’s shade begin to lean away in opposite directions.

Finally, we wanted to see whether we could replicate the zigzag pattern we’d observed with the real sunflowers in our model.

First, we set the model sunflowers to make small circumnutations. Their shade avoidance responses pushed them away from each other, but that wasn’t enough to produce the zigzag – the model plants stayed stuck in a line. In physics, we would call this a “frustrated” system.

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Then, we set the plants to make large circumnutations. The plants started moving in random patterns that often brought the plants closer together rather than farther apart. Again, no zigzag pattern like we’d seen in the field.

But when we set the model plants to make moderately large movements, similar to our experimental measurements, the plants could self-organize into a zigzag pattern that gave each sunflower optimal exposure to light.

So, we showed that these random, irregular movements helped the plants explore their surroundings to find desirable arrangements that benefited their growth.

Plants are much more dynamic than people give them credit for. By taking the time to follow them, scientists and farmers can unlock their secrets and use plants’ movement to their advantage.The Conversation

Chantal Nguyen, Postdoctoral Associate at the BioFrontiers Institute, University of Colorado Boulder

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