Vinny Negi, University of Pittsburgh

Diabetes develops when the body fails to manage its blood glucose levels. One form of diabetes causes the body to not produce insulin at all. Called Type 1 diabetes, or T1D, this autoimmune disease happens when the body’s defense system mistakes its own insulin-producing cells as foreign and kills them. On average, T1D can lead patients to lose an average of 32 years of healthy life.

Current treatment for T1D involves lifelong insulin injections. While effective, patients taking insulin risk developing low blood glucose levels, which can cause symptoms such as shakiness, irritability, hunger, confusion and dizziness. Severe cases can result in seizures or unconsciousness. Real-time blood glucose monitors and injection devices can help avoid low blood sugar levels by controlling insulin release, but they don’t work for some patients.

For these patients, a treatment called islet transplantation can help better control blood glucose by giving them both new insulin-producing cells as well as cells that prevent glucose levels from falling too low. However, it is limited by donor availability and the need to use immunosuppressive drugs. Only about 10% of T1D patients are eligible for islet transplants.

In my work as a diabetes researcher, my colleagues and I have found that making islets from stem cells can help overcome transplantation challenges.

History of islet transplantation

Islet transplantation for Type 1 diabetes was FDA approved in 2023 after more than a century of investigation.

Insulin-producing cells, also called beta cells, are located in regions of the pancreas called islets of Langerhans. They are present in clusters of cells that produce other hormones involved in metabolism, such as glucagon, which increases blood glucose levels; somatostatin, which inhibits insulin and glucagon; and ghrelin, which signals hunger. Anatomist Paul Langerhans discovered islets in 1869 while studying the microscopic anatomy of the pancreas, observing that these cell clusters stained distinctly from other cells.

The road to islet transplantation has faced many hurdles since pathologist Gustave-Édouard Laguesse first speculated about the role islets play in hormone production in the late 19th century. In 1893, researchers attempted to treat a 13-year-old boy dying of diabetes with a sheep pancreas transplant. While they saw a slight improvement in blood glucose levels, the boy died three days after the procedure.

Interest in islet transplantation was renewed in 1972, when scientist Paul E. Lacy successfully transplanted islets in a diabetic rat. After that, many research groups tried islet transplantation in people, with no or limited success.

In 1999, transplant surgeon James Shapiro and his team successfully transplanted islets in seven patients in Edmonton, Canada, by transplanting a large number of islets from two to three donors at once and using immunosuppressive drugs. Through the Edmonton protocol, these patients were able to manage their diabetes without insulin for a year. By 2012, over 1,800 patients underwent islet transplants based on this technique, and about 90% survived through seven years of follow-up. The first FDA-approved islet transplant therapy is based on the Edmonton protocol.

Stem cells as a source of islets

Islet transplantation is now considered a minor surgery, where islets are injected into a vein in the liver using a catheter. As simple as it may seem, there are many challenges associated with the procedure, including its high cost and a limited availability of donor islets. Transplantation also requires lifelong use of immunosuppressive drugs that allow the foreign islets to live and function in the body. But the use of immunosuppressants also increases the risk of other infections.

To overcome these challenges, researchers are looking into using stem cells to create an unlimited source of islets.

There are two kinds of stem cells scientists are using for islet transplants: embryonic stem cells, or ESCs, and induced pluripotent stem cells, or iPSCs. Both types can mature into islets in the lab.

Each has benefits and drawbacks.

There are ethical concerns regarding ESCs, since they are obtained from dead human embryos. Transplanting ESCs would still require immunosuppressive drugs, limiting their use. Thus, researchers are working to either encapsulate or make mutations in ESC islets to protect them from the body’s immune system.

Conversely, iPSCs are obtained from skin, blood or fat cells of the patient undergoing transplantation. Since the transplant involves the patient’s own cells, it bypasses the need for immunosuppressive drugs. But the cost of generating iPSC islets for each patient is a major barrier.

Stem cell islet challenges

While iPSCs could theoretically avoid the need for immunosuppressive drugs, this method still needs to be tested in the clinic.

T1D patients who have genetic mutations causing the disease currently cannot use iPSC islets, since the cells that would be taken to create stem cells may also carry the same disease-causing mutation of their islet cells. Many available gene-editing tools could potentially remove those mutations and generate functional iPSC islets.

In addition to the challenge of genetic tweaking, price is a major issue for islet transplantation. Transplanting islets made from stem cells is more expensive than insulin therapy because of higher manufacturing costs. Efforts to scale up the process and make it more cost effective include creating biobanks for iPSC matching. This would allow iPSC islets to be used for more than one patient, reducing costs by avoiding the need to generate freshly modified islets for each patient. Embryonic stem cell islets have a similar advantage, as the same batch of cells can be used for all patients.

There is also a risk of tumors forming from these stem cell islets after transplantation. So far, lab studies on rodents and clinical trials in people have rarely shown any cancer. This suggests the chances of these cells forming a tumor are low.

That being said, many rounds of research and development are required before stem cell islets can be used in the clinic. It is a laborious trek, but I believe a few more optimizations can help researchers beat diabetes and save lives.

Article updated to clarify that Type 1 diabetes causes the body to not produce insulin.

Vinny Negi, Research Scientist in Endocrinology and Metabolism, University of Pittsburgh

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

Nicholas Money, Miami University

Mold growth in your home can be unsettling. Blackened spots and dusty patches on the walls are signs that something is amiss, but it is important to distinguish between mold growth that is a nuisance and mold growth that may be harmful.

There are more than 1 million species of fungi. Some are used to produce important medications. Others can cause life-threatening infections when they grow in the body.

Microscopic fungi that grow in homes are a problem because they can trigger asthma and other allergies. In my work as a fungal biologist, however, I have yet to encounter robust scientific evidence to support claims that indoor molds are responsible for other serious illnesses.

What are molds?

Molds are microscopic fungi that grow on everything. This may sound like an exaggeration, but pick any material and a mold will be there, from the leaves on your houseplant to the grain in your pantry and every pinch of soil on the ground. They form splotches on the outside of buildings, grow in crevices on concrete paths and roads, and even live peacefully on our bodies.

Molds are important players in life on Earth. They’re great recyclers that fertilize the planet with fresh nutrients as they rot organic materials. Mildew is another word for mold.

Fungi, including molds, produce microscopic, seed-like particles called spores that spread in the air. Mold spores are produced on stalks. There are so many of these spores that you inhale them with every breath. Thousands could fit within the period at the end of this sentence.

When these spores land on surfaces, they germinate to form threads that elongate, and they branch to create spidery colonies that expand into circular patches. After mold colonies have grown for a few days, they start producing a new generation of spores.

Where do indoor molds grow?

Molds can grow in any building. Even in the cleanest homes, there will be traces of mold growth beneath bathroom and kitchen sinks. They’re also likely to grow on shower curtains, as well as in sink drains, dishwashers and washing machines.

Molds grow wherever water collects, but they become a problem in buildings only when there is a persistent plumbing leak, or in flooded homes.

There are many species of indoor molds, which an expert can identify by looking at their spores with a microscope.

The types of molds that grow in homes include species of Aspergillus and Penicillium, which are difficult to tell apart. These are joined by Cladosporium and Chaetomium, which loves to grow on wet carpets.

Stachybotrys is another common fungus in homes. I’ve found it under plant pots in my living room.

When does mold growth become a problem?

Problematic mold growth occurs when drywall becomes soaked through and mold colonies develop into large, brown or black patches. If the damaged area is smaller than a pizza box, you can probably clean it yourself. But more extensive mold growth often requires removing and replacing the drywall. Either way, solving the plumbing leak or protecting the home from flooding is essential to prevent the mold from returning.

In cases of severe mold growth, you can hire an indoor air quality specialist to measure the concentration of airborne spores in the home. Low concentrations of spores are normal and present no hazard, but high concentrations of spores can cause allergies.

During air testing, a specialist will sample the air inside and outside the home on the same day. If the level of spores measured in indoor air is much higher than the level measured in the outdoor air, molds are likely growing somewhere inside the home.

Another indication of mold growth inside the home is the presence of different kinds of molds in the outdoor and indoor air. Professional air sampling will identify both of these issues.

Why are indoor molds a problem?

Indoor molds present three problems. First, they create an unappealing living space by discoloring surfaces and creating unpleasant, moldy smells. Second, their spores, which float in the air, can cause asthma and allergic rhinitis, or hay fever.

Finally, some molds produce poisonous chemicals called mycotoxins. There is no scientific evidence linking mycotoxins produced by indoor molds to illnesses among homeowners. But mycotoxins could cause problems in the most severe cases of mold damage – usually in flooded homes. Irrespective of mycotoxin problems, you should treat mold growth in these more severe situations to prevent allergies.

The mold called Stachybotrys has been called the toxic black mold since its growth was linked to lung bleeding in infants in Cleveland in the 1990s. This fungus grows on drywall when it becomes soaked with water and produces a range of mycotoxins.

Black mold spores are sticky and are not blown into the air very easily. This behavior limits the number of spores that anyone around will likely inhale, and it means that any dose of the toxins you might absorb from indoor mold is vanishingly small. But the developing lungs of babies and children are particularly vulnerable to damage. This is why it is important to limit mold growth in homes and address the sources of moisture that stimulate its development.

Knowing when indoor molds require attention is a useful skill for every homeowner and can allow them to avoid unnecessary stress.

Nicholas Money, Professor of Biology, Miami University

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

Roger J. Kreuz, University of Memphis

How will the internet evolve in the coming decades?

Fiction writers have explored some possibilities.

In his 2019 novel “Fall,” science fiction author Neal Stephenson imagined a near future in which the internet still exists. But it has become so polluted with misinformation, disinformation and advertising that it is largely unusable.

Characters in Stephenson’s novel deal with this problem by subscribing to “edit streams” – human-selected news and information that can be considered trustworthy.

The drawback is that only the wealthy can afford such bespoke services, leaving most of humanity to consume low-quality, noncurated online content.

To some extent, this has already happened: Many news organizations, such as The New York Times and The Wall Street Journal, have placed their curated content behind paywalls. Meanwhile, misinformation festers on social media platforms like X and TikTok.

Stephenson’s record as a prognosticator has been impressive – he anticipated the metaverse in his 1992 novel “Snow Crash,” and a key plot element of his “Diamond Age,” released in 1995, is an interactive primer that functions much like a chatbot.

On the surface, chatbots seem to provide a solution to the misinformation epidemic. By dispensing factual content, chatbots could supply alternative sources of high-quality information that aren’t cordoned off by paywalls.

Ironically, however, the output of these chatbots may represent the greatest danger to the future of the web – one that was hinted at decades earlier by Argentine writer Jorge Luis Borges.

The rise of the chatbots

Today, a significant fraction of the internet still consists of factual and ostensibly truthful content, such as articles and books that have been peer-reviewed, fact-checked or vetted in some way.

The developers of large language models, or LLMs – the engines that power bots like ChatGPT, Copilot and Gemini – have taken advantage of this resource.

To perform their magic, however, these models must ingest immense quantities of high-quality text for training purposes. A vast amount of verbiage has already been scraped from online sources and fed to the fledgling LLMs.

The problem is that the web, enormous as it is, is a finite resource. High-quality text that hasn’t already been strip-mined is becoming scarce, leading to what The New York Times called an “emerging crisis in content.”

This has forced companies like OpenAI to enter into agreements with publishers to obtain even more raw material for their ravenous bots. But according to one prediction, a shortage of additional high-quality training data may strike as early as 2026.

As the output of chatbots ends up online, these second-generation texts – complete with made-up information called “hallucinations,” as well as outright errors, such as suggestions to put glue on your pizza – will further pollute the web.

And if a chatbot hangs out with the wrong sort of people online, it can pick up their repellent views. Microsoft discovered this the hard way in 2016, when it had to pull the plug on Tay, a bot that started repeating racist and sexist content.

Over time, all of these issues could make online content even less trustworthy and less useful than it is today. In addition, LLMs that are fed a diet of low-calorie content may produce even more problematic output that also ends up on the web.

An infinite − and useless − library

It’s not hard to imagine a feedback loop that results in a continuous process of degradation as the bots feed on their own imperfect output.

A July 2024 paper published in Nature explored the consequences of training AI models on recursively generated data. It showed that “irreversible defects” can lead to “model collapse” for systems trained in this way – much like an image’s copy and a copy of that copy, and a copy of that copy, will lose fidelity to the original image.

How bad might this get?

Consider Borges’ 1941 short story “The Library of Babel.” Fifty years before computer scientist Tim Berners-Lee created the architecture for the web, Borges had already imagined an analog equivalent.

In his 3,000-word story, the writer imagines a world consisting of an enormous and possibly infinite number of hexagonal rooms. The bookshelves in each room hold uniform volumes that must, its inhabitants intuit, contain every possible permutation of letters in their alphabet.

Initially, this realization sparks joy: By definition, there must exist books that detail the future of humanity and the meaning of life.

The inhabitants search for such books, only to discover that the vast majority contain nothing but meaningless combinations of letters. The truth is out there –but so is every conceivable falsehood. And all of it is embedded in an inconceivably vast amount of gibberish.

Even after centuries of searching, only a few meaningful fragments are found. And even then, there is no way to determine whether these coherent texts are truths or lies. Hope turns into despair.

Will the web become so polluted that only the wealthy can afford accurate and reliable information? Or will an infinite number of chatbots produce so much tainted verbiage that finding accurate information online becomes like searching for a needle in a haystack?

The internet is often described as one of humanity’s great achievements. But like any other resource, it’s important to give serious thought to how it is maintained and managed – lest we end up confronting the dystopian vision imagined by Borges.

Roger J. Kreuz, Associate Dean and Professor of Psychology, University of Memphis

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